Abstract: Objective The clinical application of doxorubicin ( Dox ) is limited by its dose-dependent cardiotoxicity. This study was established to elucidate the mechanism by which Quercetin ( Que) acts in Dox-induced cytotoxicity. Methods Mice were randomly divided into a Con group, Que group, Dox group and Dox-Que group. Neonatal mouse cardiomyocytes were isolated and randomly divided into a Dox-Vehicle group, Dox-Que group, Dox-Que-SB group, Dox-SB group and Dox-3 MA group. Cell viability was detected by CCK-8 kit, while ATP content and ROS production were determined simultaneously. In addition, Western blot was used to determine the expression of mitophagy marker proteins. Results In vivo studies confirmed that Que can reduce Dox-induced cardiotoxicity by inhibiting mitophagy and reducing myocardial fibrosis. In vitro studies showed that Dox treatment significantly reduced the cell activity of neonatal mouse cardiomyocytes and ATP content, increased ROS production, and significantly activated mitophagy (P< 0.05). Que pretreatment alleviated Dox-induced cardiomyocyte injury by inhibiting the activation of mitophagy while reducing ROS production and increasing mitochondrial ATP content. Our study further confirmed that the inhibitory effect of Que on mitophagy was mediated by the Pink1 / Parkin-dependent signaling pathway, and that SB treatment partially offset the protective effect of Que on Dox-induced cardiotoxicity by activating mitophagy. Conclusions Que can inhibit Pink1 / Parkin-mediated mitophagy activation, promote ATP production, reduce ROS production and alleviate Dox-induced cardiotoxicity.

Abstract: Objective To explore the modeling elements of an animal model of chronic obstructive pulmonary disease, which may provide a method ological reference to establish this model. Methods We searched for literature from January 2011 to July 2021 in CNKI and Wanfang databases using an animal model of chronic obstructive pulmonary disease combined with animal models as the subject words, and sorted out the animal species and model involved in the model. Then, we established a database for statistical analysis with method, cycles, detection indicators, administration time and positive control drugs. Results A total of 176 articles were included. The most commonly used animals for the COPD model were SD rats (83 times, 47. 16%), Wistar rats (59 times, 33. 52%), and C57 mice (14 times, 7. 95%), which tended to be male (140 times, 79. 55%). Most modeling method were smoke exposure combined with lipopolysaccharide (91 times, 52%) or simple smoke exposure (34 times, 19. 43%). The modeling cycle was mostly within 3 months (147, 83. 52%). The most detected indicators were lung histopathology ( 137 times, 24. 82%), lung function ( 79 times, 14. 31%), general condition (63 times, 11. 41%), and alveolar lavage fluid (56 times, 10. 14%). Conclusions Using SD/ Wistar rats or C57 mice as experimental animals under smoke exposure combined with lipopolysaccharide instillation or simple smoke exposure within 3 months effectively improves the success rate of COPD models. Model evaluation indicators suggest that the result of lung histopathology, lung function, general condition and alveolar lavage fluid should be integrated.

Abstract: Objective We investigated the inhibitory effect of Forsythia suspensa extract ( FSE ) on lipopolysaccharide ( LPS)-induced inflammation and establishment of an LPS-induced polarization model of RAW264. 7 cells. Methods MTT assays were used to assess cytotoxic effects of FSE and LPS on RAW264. 7 cells. Inverted microscopy was used to assess morphological changes of cells after stimulation with LPS and various concentrations of FSE. An enzyme marker was used to detect nitric oxide (NO) in culture supernatants. Fluorescence microscopy was used to detect intracellular reactive oxygen species (ROS) and apoptosis. ; Real-time PCR was used to detect iNOS expression in macrophages. iNOS, TNF-α, IL-1β, IL-6, IL-10, Arginase-1 and CD206 mRNA expression was measured by Real-time PCR. Results FSE was not cytotoxic at 50 μg / mL. At 36 h of LPS stimulation, various concentrations of FSE inhibited LPS-induced morphological changes, NO production and FSE inhibited LPS-induced the reduction of reactive oxygen species (ROS) and apoptosis. Expression of M1-type marker genes (TNF-α, IL-1β, iNOS and IL-6) in RAW264. 7 cells was significantly increased after treatment with various concentrations (100, 250, 500 and 750 ng / mL) of LPS for 24 h or with 500 ng / mL LPS for various times. The mRNA levels of M2 marker genes ( IL-10, Arginase-1 and CD206) were significantly decreased in RAW264. 7 cells. FSE decreased the expression of LPS-induced M1 marker genes and increased expression of M2 marker genes. Conclusions FSE inhibits LPS-induced inflammatory responses by inhibiting RAW264. 7 cell apoptosis and promoting polarization.

Abstract: Objective To observe the therapeutic effect of Zhenwu decoction on myocardial pathomorphology and cardiomyocyte apoptosis in rats with heart failure induced by coronary artery ligation, and to explore its effect on apoptosis- related proteins and the PI3K-AKT signaling pathway. Methods At 4 weeks after the operation, surviving rats were randomly divided into six groups with seven rats in each group as follows. (1) Sham operation group: normal saline was administered intragastrically for 28 days at 4 weeks after the operation. (2) model group: normal saline was administered intragastrically for 28 days after 4 weeks. (3) positive control group: 5 mg / kg losartan potassium was administered for 28 days after 4 weeks. ( 4) Zhenwu decoction low dose group: after 4 weeks, 6 g / kg Zhenwu decoction crude drug was administered for 28 days. ( 5 ) Zhenwu decoction middle dose group: 12 g / kg Zhenwu decoction crude drug was administered intragastrically for 28 days after 4 weeks. (6) Zhenwu decoction high dose group: 18 g / kg Zhenwu decoction crude drug was administered intragastrically for 28 days after 4 weeks. Changes in the electrocardiogram, color ultrasound, cardiomyocyte apoptosis, myocardial morphology, PI3K, AKT1 and p-AKT1 protein levels in myocardial tissue, immunohistochemical changes of Bax, Bcl-2, caspase 3, 8, 9 and BNP in the abdominal aorta were observed before and after modeling. Results ( 1) The ST segment of the heart failure model was elevated after coronary artery ligation, indicating that model establishment was successful. (2)The left ventricular mass index and BNP level of heart failure rats were increased significantly, and LVEF and LVFS were decreased significantly, whereas the left the ventricular mass index, BNP level, LVEF and LVFS were improved in the other groups. ( 3) Myocardial fibers in the model group were disordered and broken accompanied by cardiomyocyte swelling, hypertrophy. and inflammatory cell infiltration, which were relieved to various degrees in the other groups. Apoptosis in the model group was significant, which was alleviated after by Zhenwu decoction and positive control group drugs. (4)Compared with the model group, Bcl-2 was increased, and Bax and Caspase 3, 8, 9 were decreased in each treatment group. There was no significant difference in protein expression between Zhenwu decoction middle dose and sham operation groups. (5)Compared with the sham operation group, PI3K, p-AKT1 and AKT1 expression in the model group was increased, and Zhenwu decoction suppressed protein expression of PI3K, p- AKT1 and AKT1. Conclusions Zhenwu decoction reduces cardiomyocyte apoptosis and myocardial pathological changes in HF rats by regulating the PI3K-AKT pathway, enhancing myocardial contractility, and delaying the progression of heart failure.

Abstract: Objective To investigate the effect of PD98059 on epithelial-mesenchymal transition ( EMT) of transforming growth factor β1 ( TGF-β1)-induced human bronchial epithelial cells BEAS-2B and the possible molecular mechanism. Methods Human bronchial epithelial cells (BEAS-2B) were used for the BEAS-2B EMT model established with TGF-β1, and the ERK1 / 2 inhibitor PD98059 was used to explore whether inhibition of ERK/ MAPK signal transduction affects the EMT process. Immunofluorescence was used to detect the expression and location of α-SMA protein in the BEAS-2B airway remodeling model. CCK-8 assays were used to assess the cell survival rate. An Edu proliferation assay was used to assess cell proliferation. Transwell assays were used to assess cell migration. Western blott was used to detect the expression of EMT marker proteins and activation of the ERK/ MAPK pathway. Results Compared with the control group, α-SMA expression in the model group was increased, and α-SMA was expressed in the cytoplasm of BEAS- 2B cells. Cotreatment with 40 μmol / L PD98059 and 5 ng / mL TGF-β1 inhibited BEAS-2B cell growth (P<0. 05). There was no significant difference in Edu-positive cells among the three groups (P>0.05). Compared with the normal group, the number of migrating cells (P<0.05), expression of EMT marker proteins (P<0.05), and expression of p-ERK protein were increased in the model group (P<0.05). PD98059 significantly reduced the number of migrating cells (P<0.05) and inhibited the expression of EMT marker proteins ( P< 0.05) and activation of the ERK pathway ( P< 0.05). Conclusions TGF-β1 promotes the EMT of human bronchial epithelial cells via the ERK/ MAPK pathway. PD98059 inhibits EMT of bronchial epithelial cells by suppressing activation of the ERK/ MAPK pathway.

Abstract: Objective This study aimed to explore the effects of different exercise modes on skeletal muscle growth factors MSTN and IGF-1 in rats and to provide a theoretical basis for choosing appropriate exercise modes to improve skeletal muscle function. Methods Forty-eight SD rats were randomly divided into four groups, each with 12 rats, namely quiet control, continuous swimming exercise, high-intensity intermittent swimming exercise, and ladder exercise groups. After 8 weeks of exercise training, rats were sacrificed by overdosed anesthesia together with the quiet control group, and samples were collected for testing. The body weight and gastrocnemius muscle weight of each group were recorded. Cross- sectional area changes of the gastrocnemius muscle were observed by HE staining. Serum levels of MSTN, IGF-1 and insulin were measured by ELISA. MSTN, IGF-1 and p70S6K expression in the gastrocnemius muscle of rats was detected by Western blot. Results The weights of rats in the three exercise groups were significantly lower than that of the quiet control group (P<0.01). The weight of the gastrocnemius in the continuous swimming exercise group was significantly lower than that of the quiet control group (P<0.05), and the weight of the gastrocnemius in the other two groups did not change significantly (P>0.05). The gastrocnemius cross-sectional area of the three exercise groups was significantly lower than that of the quiet control group (P<0.05). The gastrocnemius cross-sectional area of ladder exercise and high-intensity intermittent exercise groups was significantly higher than that of the continuous swimming group (P<0.05). Serum IGF-1 levels of the three exercise groups were significantly lower than that of the quiet control group (P<0.01), while MSTN and insulin levels did not change significantly. MSTN protein expression in the gastrocnemius of the ladder exercise group was significantly lower than that of the quiet control group ( P< 0.01), while IGF-1 and p70s6k protein expression was significantly higher than in the quiet control group ( P< 0.01). p70S6K protein expression in the gastrocnemius of the continuous swimming exercise group was also significantly higher than that in the quiet control group ( P< 0.05 ). Conclusions Ladder exercise and high-intensity intermittent swimming exercise both increased the gastrocnemius mass index, but their effects on MSTN and IGF1 in skeletal muscle were different. Ladder exercise downregulated MSTN expression and upregulated IGF1 and p70S6K expression, whereas high-intensity intermittent swimming exercise had no significant effect on MSTN, IGF-1 or p70S6K in skeletal muscle. Ladder climbing may increase the cross-sectional area of gastrocnemius muscle by reducing MSTN and increasing IGF-1 and p70S6K.

Abstract: Objective To study the static inhalation toxicity of plastic racetrack surface materials in rats. Methods SD rats that passed quarantine inspection were randomly divided into four groups, namely 30 day normal control, 30 day exposure group, 90 day normal control, and 90 day exposure groups with 16 males and females in each group. Rats were exposed to gases by inhalation for 30 or 90 days. At the end of inhalation exposure, blood coagulation, blood routine test, blood biochemistry, organ coefficient, and organ pathology were assessed. Results Compared with normal control group of the same sex, thrombin time of male rats was shortened in the 30 day exposure group (P<0.05) and activated partial thrombin time of female rats was prolonged in the 90 day exposure group (P<0.01). Serum Ca and P were decreased in female rats (P<0.05, P<0.01), and serum creatinine and urea nitrogen (BUN) in rats were increased in the 30 day exposure group. In the 90 day exposure group, serum BUN and P were increased (P<0.05, P<0.01), Na and Cl were decreased of female rats (P<0.01), whereas serum BUN and total protein were increased in male rats (P< 0.05). The adrenal coefficient of male rats was increased in 30 and 90 day exposure groups (P<0.01). In the 30 day exposure group, there were three cases of mild steatosis of hepatocytes in the hepatic portal area, three cases of exfoliation of the bronchoalveolar epithelium, one case of renal cyst, and one case of individual convoluted tubule atrophy of testis. In the 90 day exposure group, there were six cases of mild steatosis of hepatocytes in the hepatic portal area, two cases of exfoliation of the bronchoalveolar epithelium, one case of cellular focal hypertrophy of adrenal zona fasciculata, two cases of individual convoluted tubule atrophy of the testis, two cases of individual glomerular telangiectasia of the kidney, one case of renal cyst, four cases of hyaline cast of the kidney, one case of mineralization, and one case of hydronephrosis. Conclusions The effects on the liver, lung, testis, and kidney of SD rats were slight after 30 days of inhalation exposure, while kidney damage was aggravated after 90 days of inhalation exposure.

Abstract: Objective To observe the role and mechanism of miR-30b in apoptosis of vascular smooth muscle cells induced by high phosphorus. Methods VSMCs from the rat thoracic aorta were cultured in vitro and divided into a normal group and high phosphorus group stimulated by 10 mmol / L β-glycerophosphate. Expression of miR-30b in VSMCs was quantified by Real-time PCR, and expression of pro-apoptotic protein BAX and anti-apoptotic protein Bcl-2 was determined by Western blot. Cell proliferation was assessed by MTT assays, and apoptosis was detected by flow cytometry. To verify the effect of miR-30b on VSMCs apoptosis, inhibitor-30b and mimic-30b were applied to observe changes in proliferation and apoptosis of VSMCs and expression of BAX and Bcl-2. Results (1)The effect of high phosphorus on apoptosis of VSMCs: Flow cytometry showed that apoptosis cells of VSMCs in high phosphorus group increased significantly (P<0.05). The results of MTT showed that the proliferation of cells in high phosphorus group decreased ( P< 0.05). The expression of BAX increased and Bcl-2 decreased in high phosphorus group (P<0.05). The expression of miR-30b in high phosphorus group decreased significantly (P<0.05). (2) Effect of miR-30b on apoptosis of VSMCs: After transfection of inhibitor-30b, the number of apoptotic cells in VSMCs increased significantly (P<0.05). After transfection of inhibitor-30b, MTT assay showed that cell proliferation decreased (P<0.05). The expression of BAX increased and the expression of Bcl-2 decreased after transfection of inhibitor-30b (P<0.05). After mimic-30b transfection, the apoptotic cells of VSMCs decreased significantly (P<0.05). After transfection of mimic-30b, the expression of BAX decreased and the expression of Bcl-2 increased (P<0.05). Conclusions High phosphorus induces apoptosis. A possible mechanism is that high phosphorus inhibits miR-30b expression and then promotes expression of apoptosis gene BAX and decreases expression of anti-apoptosis gene Bcl-2, which leads to VSMCs apoptosis.

Abstract: Objective To assess miR-219a-5p expression and its promoter methylation level in gastric cancer and adjacent tissues, and to explore its effect on the biological functions of gastric cancer cell lines. Methods The expression and methylation level of miR-219a-5p in gastric cancer and adjacent tissues were detected by qPCR and MSP. Proliferation and apoptosis of gastric cancer cells were detected by Cell Counting Kit-8 assays and flow cytometry after overexpression of miR-219a-5p. Results MiR-219a-5p expression was generally downregulated in gastric cancer tissues. The relative expression of miR-219a-5p in cancer tissues (0. 769 ± 0. 95) was significantly lower than that in adjacent tissues (2. 114 ± 5. 10) (P<0.05). The DNA methylation level in the miR-219a-5p-downregulated group was significantly higher than that in the miR-219a-5p-upregulated group. Proliferation and invasion of MGC-803 cells overexpressing miR-219a-5p were inhibited significantly ( P< 0.05), apoptosis in the overexpression group was increased significantly ( P< 0.05), and expression of apoptosis-related protein caspase-3 was significantly higher ( P< 0.05). Conclusions MiR-219a-5p is generally underexpressed by methylation in gastric cancer tissue, and inhibits cell proliferation and migration, promotes apoptosis, and play a role similar to tumor suppressor genes. It is expected to become a new target for diagnosis and treatment of gastric cancer.

Abstract: Objective To investigate the neuroprotective effect of soyasaponin Bb ( SSBb) pretreatment in cerebral ischemia / reperfusion ( I/ R) rats. Methods SD rats were divided into sham, model, and low- and high-dose SSBb pretreatment groups with 15 rats each. A rat model of middle cerebral artery occlusion (MCAO) was established by suture occlusion, and reperfusion was performed 2 h after occlusion to simulate brain I/ R. Low- and high-dose SSBb pretreatment groups were administered 20 and 50 mg / kg SSBb by gavage, respectively, at 1 h before MCAO. At 24 h after reperfusion, neurological deficits were assessed by the modified neurological severity score, and cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Microtubule-associated protein-2 staining was used to assess neuronal damage. Brain water content was measured by the dry / wet weight. Tumor necrosis factor-α (TNF-α) expression in ischemic penumbra was measured by immunofluorescence. Postsynaptic density-95 ( PSD-95 ), synapsin I and synaptotagmin expression was detected by Western blot. Results Compared with the model group, low- and high-dose SSBb pretreatment significantly improved neurological dysfunction, alleviated cerebral edema and cerebral infarction in MCAO model rats, and decreased expression of TNF-α, PSD-95, synapsin I and synaptotagmin in ischemic penumbra (P<0. 01 or P< 0. 001). The effects in the high-dose group were most significant ( P< 0. 001). Conclusions SSBb pretreatment has a neuroprotective effect in rats with cerebral I/ R injury.

Abstract: Objective To observe the protective effect of resveratrol in mice with premature ovarian failure and to explore its possible mechanism. Methods Forty two-month-old female mice were randomly divided into four groups: control group (Control), model group, 20 mg / kg RES group, and 40 mg / kg RES group with 10 mice in each group. Changes in body weight and the ovarian weight coefficient were assessed. Follicle number changes in mouse ovarian tissue were observed by HE staining. Relative mRNA expression of cyclin D1, Wnt1 and β-catenin in ovarian tissues was measured by RT-qPCR. β-catenin protein expression in ovarian tissue was detected by immunohistochemical staining. Mvh, Oct4, SOD2, Nrf2, Bax and Bcl-2 protein expression in ovarian tissues was detected by Western blot. Results Body weight, ovary weight, and ovary / mouse weight ratio in 20 and 40 mg / kg RES groups were higher than those in the model group. Compared with the model group, the number of primordial follicles was increased and the number of atresia follicles was decreased in 20 and 40 mg / kg RES groups (P<0. 05), while mRNA expression of cyclin D1, Wnt1 and β- catenin was increased in ovarian tissues (P<0. 05). Compared with the model group, β-catenin protein expression was increased in ovarian tissues in 20 and 40 mg / kg RES groups in a concentration-dependent manner. Compared with the model group, Mvh, Oct4, SOD2, Nrf2 and Bcl-2 protein expression was increased and Bax expression was decreased in ovarian tissues of 20 and 40 mg / kg RES groups (P<0.01). Conclusions The protective effect of resveratrol in mice with premature ovarian failure may be related to inhibition of ovarian cell apoptosis and activation of the Wnt / β-catenin pathway to promote recovery of ovarian functions.

Abstract: Objective To establish a rat model of acute pulmonary edema under high-altitude hypobaric hypoxia and a cold environment, and to explore the effect of cold factors on the formation of acute high-altitude pulmonary edema. Methods One-hundred healthy male SD rats were randomly divided into two groups (n= 50): HN and HC groups. Each group was divided into five subgroups ( n= 10) with five time points: 0, 24, 48, 72 and 120 h. The two groups of rats were placed in an artificial experimental cabin to simulate hypobaric hypoxia at an altitude of 7000 m, different ambient temperatures were set, the rats were anesthetized at the corresponding time points, and alveolar lavage fluid and lung tissue were collected. The BALF protein concentration and W/ D ratio of lung tissue were measured. The lung tissue was sectioned and stained with HE to observe pathological changes. Results The W/ D ratio of lung tissue was increased in HN and HC groups. The W/ D ratio of lung tissue in the HN group reached the highest at 72 h, and that in the HC group reached the highest at 48 h. At 48, 72 and 120 h, the W/ D ratio of lung tissue in the high-altitude cold group was significantly higher than that in the HN group (P<0. 05). The trend in the changes of the BALF protein concentration and lung pathology was the same as that of the lung W/ D ratio. The BALF protein concentration and lung injury score in the HN group reached the highest at 72 h, which were ( 0. 2802 ± 0. 0243) and ( 1. 7778 ± 0. 4410) mg / mL respectively, and the BALF protein concentration and lung injury score in HC group reached the highest at 48 h, and their values were (0. 3352 ± 0. 0204) and (2. 8889 ± 1. 0541) mg / mL respectively. At 48, 72 and 120 h, the BALF protein concentration and lung injury score in the HC were higher than those in the HN group ( P< 0. 05). Conclusions In the simulated hypobaric hypoxia environment at high altitude of 7000 m, the SD rat model of acute high-altitude pulmonary edema was successfully established after exposure to cold conditions ( daytime temperature: 15℃ ; nighttime temperature: 5℃ ) for 48 h, but it required 72 h at normal temperature. This study suggests that cold factors promote the occurrence and development of acute high-altitude pulmonary edema.

Abstract: Objective To investigate the effects of quercetin on interstitial transformation, inflammation, and the NOX4-P62 signaling pathway in lung tissue of rats with pulmonary fibrosis to provide an experimental basis for further elucidating the mechanism of quercetin in pulmonary fibrosis. Methods Rats were divided into control, BLM and BLM+ QUE groups. The appearance of lung tissue in each group was observed on days 10, 20 and 30 after modeling. Pulmonary fibrosis was evaluated by HE staining. NOX4 and P62 in lung tissue, and α-SMA and E-cadherin in A549 cells were detected by western blotting. TGF-β1, IL-1β and TNF-α were measured by ELISA. Results Symptoms in the BLM+QUE group were milder than those in the BLM group on day 7, and significantly relieved on day 28. TGF-β1, IL-1β, TNF-α, NOX4 and P62 expression in the BLM+QUE group was lower than that in the BLM group on day 10 (P>0. 05), but it was much expression lower than that in the BLM group on days 14 and 28 (P<0. 05). Compared with the control group, E- cadherin and α-SMA expression in the TGF-β1 group was significantly decreased and increased, respectively (P<0. 05). Compared with the TGF-β1 group, E-cadherin and α-SMA expression in the TGF-β1 + QUE group were significantly increased and decreased, respectively ( P< 0. 05 ). Conclusions Quercetin inhibits TGF-β1. EMT of A549 cells alleviates the inflammatory reaction and pulmonary fibrosis induced by bleomycin in rats. Autophagy is inhibited by bleomycin-induced pulmonary fibrosis in rats. Quercetin inhibits the NOX4-P62 signaling pathway, activates autophagy, and reduces pulmonary fibrosis in rats.

Abstract: Objective A sperm-specific phospholipase C zeta-1 (Plcz1^{- / -} ) gene knockout mouse was generated by the CRISPR/ Cas9 system to explore the role of the Plcz1 gene in male mouse fertility. Methods Exons 6 and 7 of the mouse Plcz1 gene were selected as target sites to design two pairs of sgRNAs. The two pairs of sgRNAs were inserted into the pX330A plasmid by the Golden Gate method to construct the pX330-sgRNA recombinant plasmid. After amplification and purification, the recombinant plasmid was microinjected into pronuclear of mouse zygote. The embryos were transferred to surrogate mother mice. After the birth of F0 generation mice, tail DNA was analyzed by PCR and sequencing. The F0 generation was mated with wild-type mice to obtain F1 generation mice. The F1 generation was bred to the F2 generation to obtain a homozygous strain of Plcz1 gene knockout mice. To analyze Plcz1^{- / -} male mouse fertility, Plcz1^{- / -} mice were mated with wild-type mice. Results The recombinant plasmid pX330-sgRNA was constructed successfully, and three Plcz1^{- / -} male mice (Plcz1^m3 , Plcz1^m4 and Plcz1^m5 ) were obtained by breeding. Target gene sequencing of the three mice showed that Plcz1^m3 had a 3078 nucleotide deletion between exons 6 and 7 of Plcz1, Plcz1^m4 had a seven nucleotide deletion in exon 7 of Plcz1, which died during feeding, and Plcz1^m5 had a one nucleotide deletion in exon 6 of Plcz1. Conclusions Plcz1^{- / -} male mice were successfully generated using the CRISPR/ Cas9 system. Plcz1^{- / -} male mice were fertile, but their fertility was significantly decreased compared with wild-type mice.

Abstract:Yanghe decoction is derived from the Qing Dynasty “Waike Quan sheng ji”, which has the effect of warming Yang and replenishing blood, dispersing cold and clearing stagnation. In accordance with traditional Chinese medicine, Yang deficiency and cold phlegm condensation are major mechanisms of malignant tumors. As a representative prescription of warming Yang and dispersing cold and stagnation, Yanghe decoction is widely used in the clinical treatment of malignant tumor, especially in Yang-deficient cancer patients. We analyzed CNKI, WanFang, VIP, SinoMed Chinese Biomedical Literature System, PubMed, Medline and Embase database from 2001 to 2021, found 225 articles with the topics of “Yanghe decoction, warming Yang method, malignant tumor (cancer), and network pharmacology”, and sorted out, and summarized 94 relevant articles. This review summarizes the mechanism of Yanghe decoction from the aspects of their theoretical origin, clinical observations, and pharmacological research to provide a scientific basis for the clinical treatment of malignant tumors.

Abstract:Chronic pharyngitis is a clinically common diffuse inflammation of the pharyngeal mucosa, submucosa, and lymphatic tissues. The incidence of chronic pharyngitis is increasing yearly, the disease duration is increasing gradually, and there is no specific treatment for chronic pharyngitis. This study summarizes the existing animal models of chronic pharyngitis on the basis of the Chinese and Western clinical characteristics of chronic pharyngitis. Clinical diagnosis of chronic pharyngitis and the diagnostic criteria were analyzed in terms of their compatibility with animal models and an evaluation system was established for the existing models to analyze the advantages and disadvantages of various animal models. The existing animal models were improved to provide ideas for the establishment of ideal animal models to promote research of chronic pharyngitis.

Abstract:Peripheral nerve injury is a major disease. Because the injury and repair mechanisms of the disease are unclear, its treatment is poor. Therefore, peripheral nerve injury has become a difficult point for orthopedics doctors. In recent years, phosphatase and tensin homologue deleted on chromosome 10 ( PTEN) has been widely studied to repair peripheral nerve injury. Here, we review the mechanism of PTEN in regulating synaptic regeneration, inflammatory and immune responses, neuronal apoptosis, neurotrophic related factors, and NF-κB, PI3K/ AKT/ mTOR and Jak / Stat signaling pathways during the repair of peripheral nerve injury to facilitate research.

Abstract:Acquired drug resistance is a major cause of high lethality in pancreatic cancer. Gemcitabine resistance is the most common in the clinic. Exploring the specific molecular mechanism of gemcitabine resistance in pancreatic cancer will facilitate using gemcitabine rationally in the clinic and improve the quality of life and survival of patients. Long non-coding RNAs (lncRNAs) play an important role in gemcitabine resistance of pancreatic cancer. Because of specific expression after drug resistance in tumors, lncRNAs have become ideal targets to restore gemcitabine sensitivity in pancreatic cancer. In this review, we summarize the specific mechanisms of various lncRNAs in gemcitabine resistance of pancreatic cancer to explore possible therapeutic targets related to lncRNA to alleviate gemcitabine resistance of pancreatic cancer.

Abstract:Primary cilia are microtubule-based organelles that sense extracellular mechanical and chemical signals, and transmit information into cells by mediating various molecular signaling pathways, which play an important role in development, cell migration, and cell differentiation. In recent years, primary cilia have been found on epithelial and mesenchymal cells of the mouse embryonic palatal process, and the primary cilia themselves and their signaling factors are closely related to palate development. Therefore, this article reviews the recent research progress on the mechanism of palatal dysplasia caused by primary cilia and related signaling pathways to provide new ideas for researchers in the fields of cleft lip and palate.

Abstract:Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) accelerates liver regeneration remarkably. However, the molecular mechanism of ALPPS remains unclear. It is necessary for in-deep research to establish a stable and reproducible ALPPS animal model under various liver disease backgrounds. This article reviews the research progress of ALPPS animal models in recent years.

Abstract:Ischemia is a kind of localized ischemic necrosis or softening caused by infarction of tissues and organs or blood supply disturbance, which often occurs in the liver, kidney, brain, and other organs. In the early stage of restoring blood supply, it often causes ischemia-reperfusion injury. Oxidative stress is a major causes of ischemia- reperfusion injury. Studies have confirmed that ischemia-reperfusion leads to the production of reactive oxygen species, which causes organ injury and dysfunction. This review summarizes the research progress of ischemia-reperfusion oxidative injury in recent years from the perspective of oxidative stress and analyzes the effect of this injury on various tissues and organs. It aims to further reveal the mechanism of oxidative injury caused by ischemia-reperfusion and provide ideas for the prevention and treatment of related diseases.