Objective To analyze the risk of bias during the experimental process and the shortcomings of the research report by evaluating the methodological and reporting quality of animal experimental studies on the prevention and treatment of precancerous lesions of gastric cancer(PLGC)using TCM compounds.To provide reference for improving the quality of animal experimental research on the prevention and treatment of PLGC with TCM compounds.Methods Experimental literature about the prevention and treatment of PLGC with TCM compounds was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Cochrane Library,Web of science and Embase from January 1,2014 to February 23,2024.SYRCLE assessment tool and ARRIVE 2.0 guideline were used to score the included literature and calculate the"low-risk"compliance rate for each item.Results Totally 213 articles were finally included,including 189 Chinese articles and 24 English articles.The SYRCLE tool score was(12.86±1.29)points,and the"low risk"compliance rate was 32.79％.The score of the necessary items of the ARRIVE 2.0 guideline was(24.15±2.80)points,and the"low risk"compliance rate was 49.08％;the score of the recommended items was(11.28±3.40)points,and the"low risk"compliance rate was 30.27％.In the SYRCLE tool evaluation,144(67.61％)studies did not elaborate on the method of generating the allocation sequence.All studies did not describe the adequacy of allocation concealment and the blinding method in the implementation of bias.Only 51 studies(23.94％)explicitly proposed the success criteria for PLGC modeling,only 66 studies(30.96％)provided detailed information on the statistical methods used,29 studies(13.62％)provided complete ethical statements,and 22 studies(10.33％)reported conflicts of interest.Conclusion There are many problems in the methodological quality and reporting quality of animal experimental literature on the prevention and treatment of PLGC with TCM compounds published from 2014 to 2024,especially the implementation of the random blinding strategy during the experimental process,the calculation details of the sample size,and the reporting of inclusion and exclusion criteria,etc.There are many deficiencies in this aspect.It is recommended to refer to the SYRCLE evaluation tool and the ARRIVE 2.0 guideline list to design and report the research plan,thereby improving the credibility and standardization of the PLGC animal experimental research results.

Objective:To investigate the gender differences in the causal relationship between testosterone-related hormones and type 2 diabetes mellitus(T2DM), and to analyze the mediating role of blood lipids in this relationship.Methods:Using two-sample Mendelian randomization(TSMR) and two-step Mendelian randomization(MR) methods, we explored the causal associations between testosterone-related hormones, T2DM, and blood lipids in different genders. The potential mediating role of blood lipids between testosterone-related hormones and T2DM was quantitatively assessed using multivariate Mendelian Randomization(MVMR).Results:In males, each standard deviation( SD) increase in genetically predicted total testosterone(TT) was associated with lower odds of T2DM( OR=0.90, 95% CI 0.82-0.97, P=0.009) and higher high-density lipoprotein-cholesterol(HDL-C) level( β=0.08 SD, 95% CI 0.03-0.13, P=0.002). In women, each SD rise in genetically predicted bioavailable testosterone(Bio-T) was associated with higher odds of T2DM( OR=1.24, 95% CI 1.10-1.40, P<0.001), lower HDL-C level( β=-0.13 SD, 95% CI -0.21--0.05, P<0.001). Mediation analysis revealed that HDL-C played a mediating role(7.83%) between Bio-T and T2DM in women. However, HDL-C showed no mediating effect between SHBG and TT levels on T2DM, and low-density lipoprotein-cholesterol(LDL-C) showed no mediating effect between TT levels on T2DM in men. Conclusions:Lower levels of TT and SHBG in men, and high levels of Bio-T in women may increase the risk of T2DM. In women, regulating HDL-C levels may offer a potential strategy for the prevention and treatment of T2DM related to Bio-T disorders.

Objective:To explore the effects of different electrical stimulations on cerebral cortex excitability, upper limb motor function, left-right coordination and counterbalance mechanisms among stroke survivors.Methods:Thirty stroke survivors with hemiplegia were randomly divided into a neuromuscular electrical stimulation (NMES) group and a contralateral control functional electrical stimulation (CCFES) group, each of 15. In addition to conventional rehabilitation treatment, the NMES group was additionally given daily 20-minute NMES to promote elbow extension and wrist extension 5 days a week for 4 weeks, while the CCFES group was given CCFES, instead. Before and after the treatment, the bilateral resting motor thresholds (RMTs), motor evoked potential (MEPs) cortical latency, MEP amplitude and inter-hemisphere asymmetry (IHA) index were measured. The Fugl-Meyer upper extremity assessment (FMA-UE) and the Hong Kong version of the functional test for hemiplegic upper extremities (FTHUE-HK) were employed to evaluate the subjects′ motor functioning. Pearson correlation coefficients relating cortical excitability with upper extremity function were computed.Results:After the treatments, significant improvement was observed in both groups in the latency and amplitude of the RMT and MEP of the affected hemisphere, the IHA value, as well as the FMA-UE and FTHUE-HK scores. The CCFES group then had scores significantly superior to those in the NMES group, on average. The improvements in the FMA-UE and FTHUE-HK scores were significantly positively correlated with the gap in IHA values and the MEP amplitude of the affected hemisphere.Conclusions:Both NMES and CCFES can improve the excitability of the affected motor cortex after a stroke. They help to restore the dynamic balance between the brain hemispheres for better motor functioning of the upper limbs. CCFES has a better therapeutic effect than NMES. The improvement in upper limb motor function is positively correlated with the increase in cortical excitability of the affected hemisphere and the normalization of inter-hemisphere asymmetry.

Objective:To explore the effects of different electrical stimulations on cerebral cortex excitability, upper limb motor function, left-right coordination and counterbalance mechanisms among stroke survivors.Methods:Thirty stroke survivors with hemiplegia were randomly divided into a neuromuscular electrical stimulation (NMES) group and a contralateral control functional electrical stimulation (CCFES) group, each of 15. In addition to conventional rehabilitation treatment, the NMES group was additionally given daily 20-minute NMES to promote elbow extension and wrist extension 5 days a week for 4 weeks, while the CCFES group was given CCFES, instead. Before and after the treatment, the bilateral resting motor thresholds (RMTs), motor evoked potential (MEPs) cortical latency, MEP amplitude and inter-hemisphere asymmetry (IHA) index were measured. The Fugl-Meyer upper extremity assessment (FMA-UE) and the Hong Kong version of the functional test for hemiplegic upper extremities (FTHUE-HK) were employed to evaluate the subjects′ motor functioning. Pearson correlation coefficients relating cortical excitability with upper extremity function were computed.Results:After the treatments, significant improvement was observed in both groups in the latency and amplitude of the RMT and MEP of the affected hemisphere, the IHA value, as well as the FMA-UE and FTHUE-HK scores. The CCFES group then had scores significantly superior to those in the NMES group, on average. The improvements in the FMA-UE and FTHUE-HK scores were significantly positively correlated with the gap in IHA values and the MEP amplitude of the affected hemisphere.Conclusions:Both NMES and CCFES can improve the excitability of the affected motor cortex after a stroke. They help to restore the dynamic balance between the brain hemispheres for better motor functioning of the upper limbs. CCFES has a better therapeutic effect than NMES. The improvement in upper limb motor function is positively correlated with the increase in cortical excitability of the affected hemisphere and the normalization of inter-hemisphere asymmetry.

Objective To analyze the risk of bias during the experimental process and the shortcomings of the research report by evaluating the methodological and reporting quality of animal experimental studies on the prevention and treatment of precancerous lesions of gastric cancer(PLGC)using TCM compounds.To provide reference for improving the quality of animal experimental research on the prevention and treatment of PLGC with TCM compounds.Methods Experimental literature about the prevention and treatment of PLGC with TCM compounds was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Cochrane Library,Web of science and Embase from January 1,2014 to February 23,2024.SYRCLE assessment tool and ARRIVE 2.0 guideline were used to score the included literature and calculate the"low-risk"compliance rate for each item.Results Totally 213 articles were finally included,including 189 Chinese articles and 24 English articles.The SYRCLE tool score was(12.86±1.29)points,and the"low risk"compliance rate was 32.79％.The score of the necessary items of the ARRIVE 2.0 guideline was(24.15±2.80)points,and the"low risk"compliance rate was 49.08％;the score of the recommended items was(11.28±3.40)points,and the"low risk"compliance rate was 30.27％.In the SYRCLE tool evaluation,144(67.61％)studies did not elaborate on the method of generating the allocation sequence.All studies did not describe the adequacy of allocation concealment and the blinding method in the implementation of bias.Only 51 studies(23.94％)explicitly proposed the success criteria for PLGC modeling,only 66 studies(30.96％)provided detailed information on the statistical methods used,29 studies(13.62％)provided complete ethical statements,and 22 studies(10.33％)reported conflicts of interest.Conclusion There are many problems in the methodological quality and reporting quality of animal experimental literature on the prevention and treatment of PLGC with TCM compounds published from 2014 to 2024,especially the implementation of the random blinding strategy during the experimental process,the calculation details of the sample size,and the reporting of inclusion and exclusion criteria,etc.There are many deficiencies in this aspect.It is recommended to refer to the SYRCLE evaluation tool and the ARRIVE 2.0 guideline list to design and report the research plan,thereby improving the credibility and standardization of the PLGC animal experimental research results.

Objective:To investigate the gender differences in the causal relationship between testosterone-related hormones and type 2 diabetes mellitus(T2DM), and to analyze the mediating role of blood lipids in this relationship.Methods:Using two-sample Mendelian randomization(TSMR) and two-step Mendelian randomization(MR) methods, we explored the causal associations between testosterone-related hormones, T2DM, and blood lipids in different genders. The potential mediating role of blood lipids between testosterone-related hormones and T2DM was quantitatively assessed using multivariate Mendelian Randomization(MVMR).Results:In males, each standard deviation( SD) increase in genetically predicted total testosterone(TT) was associated with lower odds of T2DM( OR=0.90, 95% CI 0.82-0.97, P=0.009) and higher high-density lipoprotein-cholesterol(HDL-C) level( β=0.08 SD, 95% CI 0.03-0.13, P=0.002). In women, each SD rise in genetically predicted bioavailable testosterone(Bio-T) was associated with higher odds of T2DM( OR=1.24, 95% CI 1.10-1.40, P<0.001), lower HDL-C level( β=-0.13 SD, 95% CI -0.21--0.05, P<0.001). Mediation analysis revealed that HDL-C played a mediating role(7.83%) between Bio-T and T2DM in women. However, HDL-C showed no mediating effect between SHBG and TT levels on T2DM, and low-density lipoprotein-cholesterol(LDL-C) showed no mediating effect between TT levels on T2DM in men. Conclusions:Lower levels of TT and SHBG in men, and high levels of Bio-T in women may increase the risk of T2DM. In women, regulating HDL-C levels may offer a potential strategy for the prevention and treatment of T2DM related to Bio-T disorders.

Nonalcoholic fatty liver disease （NAFLD） is one of the most common complications of type 2 diabetes mellitus （T2DM）. Cell death caused by iron-lipid disorder is a new mode of regulating programmed cell death， which is characterized by lipid peroxidation induced by the accumulation of lipid reactive oxygen species and excessive accumulation of iron ions induced by iron metabolism disorders. Among them， iron homeostasis disorder and metabolic pathway disorder are the main causes of iron-lipid disorder， which play an important role in a variety of pathological processes related to cell death. Because the liver is an important organ for iron storage and lipid metabolism， iron-lipid disorder is an ideal target for liver disease， and inhibition of iron-lipid disorder may become a new strategy for the treatment of NAFLD. However， the pathogenic relationship and mechanism between NAFLD and iron-lipid disorder have not been fully elucidated. Based on the complex molecular regulation mechanism of iron-lipid disorder， by expounding the role of iron-lipid disorder in NAFLD and its related mechanism， this paper summarizes the research status of traditional Chinese medicine on the target treatment of NAFLD in recent years， so as to provide a new perspective and point out a new direction for the treatment of NAFLD in the future.

The angiogenic microenvironment is a new blood vessel with different molecular and functional characteristics that sprouts on the original blood vessels through different mechanisms,which directly affects the process of tumor cell growth,proliferation,and migration and has an important impact on the occurrence and development of precancerous lesions of gastric cancer.Correa mode has shown that precancerous lesions of gastric cancer is the key pathological stage before the occurrence of gastric cancer,and it is of great significance to advance the prevention and treatment strategy to this stage.TCM believes that qi deficiency and blood stasis is the key pathogenesis of precancerous lesions of gastric cancer,and its basic treatment is to replenish qi and remove blood stasis,and based on the syndrome differentiation,drugs with the efficacy of nourishing yin and tonifying stomach,soothing the liver and regulating qi,resolving phlegm and dispersing lumps,and clearing heat and dampness for treatment.This article discussed the correlation between precancerous lesions of gastric cancer and angiogenic microenvironment and its regulatory pathways,and summarized the methods and mechanisms of TCM in the treatment of precancerous lesions of gastric cancer from the perspective of regulating angiogenic microenvironment-related pathways,in order to provide a reference for the treatment of precancerous lesions of gastric cancer with TCM.

Precancerous lesions of gastric cancer is a key stage in the development of gastric cancer.The reprogramming of glucose metabolism is a prominent feature of precancerous lesions of gastric cancer.Hypoxic microenvironment and hypoxia-inducible factors are important factors influencing the occurrence of glucose metabolic reprogramming.This article summarized the relationship between hypoxic microenvironment and the reprogramming of glucose metabolism in precancerous lesions of gastric cancer,and concluded the relevant research on TCM compounds and effective components to improve hypoxic microenvironment and further regulate glycolysis for the treatment of this disease.It was concluded that the mechanism may be the inhibition of angiogenesis,regulation of signaling pathways and key proteins of glycolysis,expression of multiple enzymes,reduction of lactate secretion,inhibition of cell malignant proliferation and invasion.It explored the mechanism of Chinese materia medica in improving hypoxic microenvironment and regulating glycolysis,so as to provide reference for the prevention and treatment of precancerous lesions of gastric cancer.

To investigate the effect of Zhiwei Fuwei Pills (ZWFW) on the expression of mammalian target of rapamycin (mTOR)/autophagy key molecule yeast Atg6 homologue (Beclin1)/microtubuleassociated protein 1 light chain 3 (LC3) signaling axis key molecules in gastric antrum tissue of rats with precancerous gastric lesions (PLGC). METHODS: SPF SD rats were randomly divided into normal group, model group, folic acid group, ZWFW low-dose, medium-dose, high-dose group. In addition to the normal group, the model group, folic acid group, ZWFW low-dose, medium-dose and high-dose groups, were used to establish the PLGC rat model by five factors compound modeling methods: N-methyl-N ' - nitro-n-nitroguanidine (MNNG) combined with hunger and satiation, ethanol intragastric administration, free drinking of ammonia and ranitidine feed. The rats were treated with normal saline, folic acid tablet aqueous solution (0.002 g/kg), ZWFW low-dose, medium-dose, high-dose aqueous solution (0.42, 0.84, 1.67 g/kg) for 4 weeks, and the stomach was removed by laparotomy. Hematoxylineosin (HE) staining was used to observe the histopathological changes in the antrum of rats, and real-time polymerase chain reaction (real-time PCR), Western blot (WB) and immunohistochemistry (IHC) were used to detect the expression of mammalian target of rapamycin mTOR, yeast Atg6 homologue 1 (Beclin1), microtubule-associated protein 1 light chain 3β (LC3B) mRNA and protein in the antrum of rats. RESULTS: Compared with the normal group, the Gastric antrum tissue of the model group was distended, thinner gastric wall, palegastric mucosa, atrophic and flat folds, disordered course and nodules and vegetations were visible. HE staining showed that compared with the normal group, the gastric mucosal glands in the model group were crowded and disordered, and the cell morphology was different, including a large number of goblet cells, basophilic cytoplasm, large, hyper-chromatic and irregular nuclei, and mucosal muscle infiltration and destruction. Compared with the model group, treated by ZWFW can significantly improve the pathological manifestations of gastric mucosal gland structure disorder and cell atypia. Compared with the normal group, mTOR mRNA and protein expression were significantly increased (P< 0.05) and Beclin1 and LC3B mRNA and protein expression were significantly decreased (P<0.05) in the antral tissue of rats in the model group; compared with the model group, mTOR mRNA and protein expression were decreased (P<0.05) in the medium and high dose groups of ZWFW, Beclin1 and LC3B protein expression in the antral tissue of rats in the low dose group of ZWFW and Beclin1 and LC3B mRNA and protein expression were increased (P<0.05) in the medium and high dose groups. CONCLUSION: Zhiwei Fuwei Pills can significantly improve the abnormal histopathological findings of gastric mucosa in PLGC model rats, and the mechanism may be related to the down-regulation of mTOR expression, up-regulation of Beclin1 and LC3B expression and then promoting autophagy.