ObjectiveTo explore the potential mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of regulating mitochondrial autophagy via the PTEN-induced kinase 1 （PINK1）/E3 ubiquitin ligase （Parkin） pathway. MethodsMale SD rats were subjected to abdominal aortic constriction to establish the CHF model. Twenty-four successfully modeled rats were randomly divided into the model group， sacubitril/valsartan group， and low- and high-dose Shenqi Jianxin Formula groups， with 6 rats in each group. Six other rats were set as the sham surgery group， which were only separated the abdominal aorta and then closed the abdomen. Rats in the low-dose and high-dose Shenqi Jianxin Formula groups were given intragastric administration of Shenqi Jianxin Formula suspension at doses of 4.41 g/（kg·d） and 17.64 g/（kg·d）， respectively； the sacubitril/valsartan group received intragastric administration of sacubitril/valsartan sodium tablet suspension at 10 mg/（kg·d）； the sham surgery group and the model group were given normal saline at 10 ml/（kg·d） via intragastric gavage. The intervention lasted for 4 consecutive weeks. Cardiac function indices including left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were detected， and serum brain natriuretic peptide （BNP） content was measured. HE staining and Masson staining were used to observe myocardial histopathological changes. Transmission electron microscopy was employed to examine the ultrastructure of cardiac tissues. Quantitative real-time polymerase chain reaction （Rt-qPCR） was performed to determine the mRNA expressions of PINK1/Parkin pathway-related factors and autophagy-associated proteins including Beclin-1， p62， and microtubule-associated protein 1 light chain 3 （LC3） in myocardial tissues. ResultsCompared with the sham surgery group， the model group showed significant decreases in LVEF and LVFS levels， an increase in serum BNP content， down-regulated mRNA and protein expressions of PINK1， Parkin and Beclin-1 in cardiac tissues， up-regulated mRNA and protein expressions of p62， as well as significant reductions in LC3B mRNA expression， phosphorylated PTEN-induced kinase 1 （p-PINK1） and phosphorylated E3 ubiquitin ligase （p-Parkin） protein levels， and the ratio of microtubule-associated protein 1 light chain 3-Ⅱ to microtubule-associated protein 1 light chain 3-Ⅰ （LC3Ⅱ/LC3Ⅰ） （P＜0.05）. Pathological results revealed obvious myocardial cell edema， necrosis and degeneration， increased disorder of myocardial fiber arrangement， extensive inflammatory cell infiltration， moderate to severe mitochondrial swelling， a few mitochondrial vacuolar changes， and no obvious autophagy in the field of vision in the model group. Compared with the model group， all the above indicators were significantly improved in the high-dose Shenqi Jianxin Formula group and the sacubitril/valsartan group （P＜0.05）. Moreover， the improvement of each index in the high-dose Shenqi Jianxin Formula group was superior to that in the low-dose group （P＜0.05）. In the high-dose Shenqi Jianxin Formula group， myocardial myofibrils were arranged regularly with orderly orientation， the striated structure was clear， and necrotic cells significantly reduced. ConclusionShenqi Jianxin Formula can activate the PINK1/Parkin signaling pathway in myocardial tissues， enhance mitochondrial autophagy， and clear dysfunctional mitochondria， thereby improving cardiac function and delaying the progression of CHF.

Based on the concept of "blood exhaustion" from The Inner Canon of Yellow Emperor （《黄帝内经》）， a three-stage syndrome differentiation and treatment strategy for cancer-related anorexia-cachexia syndrome is proposeed. In the cancer-induced anorexia stage， the pathogenesis is characterized by cancer consuming the spleen and stomach， leading to stagnation of transportation and transformation in the middle jiao （焦）. Treatment should focus on strengthening the spleen， promoting appetite， dispersing accumulation， and aiding digestion， with modified Zisheng Pills （资生丸） in Extensive Notes on Medicine from Xian Xing Studio （《先醒斋医学广笔记》） or Zisheng Decoction （资生汤） in Records of Chinese Medicine with Reference to Western Medicine （《医学衷中参西录》）. In the pre-cachectic stage of malnutrition， the pathogenesis involves insufficient nourishment of blood and qi with essence depletion hindering production. Treatment should focus on nourishing blood and harmonizing ying （营）， warming yang and supplementing qi， and modified Huangqi Jianzhong Decoction （黄芪建中汤） can be used. In the cachectic stage， the pathogenesis involves blood deficiency and essence exhaustion， with blood stasis obstructing the collaterals. The therapeutic approach should focus on tonifying deficiency and replenishing essence， unblocking collaterals， and removing stasis， and modified Buzhong Yiqi Decoction （补中益气汤） and Zuo Gui Beverage （左归饮） are suggested.

Objective To investigate the status and developmental trends of clinical trials for weight control drugs in China,and to provide data support for sponsors,researchers,and regulatory authorities.Methods The drug clinical trial registration and information platform of the National Medical Products Administration was utilized to search for registered clinical trials of weight control drugs from November 2012 to June 2024.The search employed"overweight","obesity",and"weight loss"as keywords.The information collected included project registration time,drug name,dosage form,drug classification,indications,trial staging,study progress,design type,lead unit,and sponsor.Microsoft Office Excel software was employed for data entry,organization,and extraction.Results A total of 95 registered clinical trials of weight control drugs were identified,comprising 40 domestic multicenter trials,47 domestic single-center trials,and 8 international multicenter trials.Regarding trial phasing,46(48.4％)were phase Ⅰ clinical trials,17(17.9％)were phase Ⅱ clinical trials,19(20.0％)were phase Ⅲ clinical trials,and 13(13.7％)were bioequivalence trials.The drug categorization encompassed 22 chemical drugs,20 biological products,and 1 traditional Chinese medicine/natural drug.Concerning drug dosage forms,there were 32 items of injectable dosage forms,8 items of tablets,2 items of capsules,and 1 item of chewable tablets.Conclusions Registered clinical trials for weight-loss medications in China are predominantly concentrated in regions with developed medical resources.Injectable biologics constitute most test drugs,with most drugs in the early stages of research and development.The examination of the safety and efficacy of these drugs remains to be substantiated,and it is anticipated that a considerable period will elapse before their approval and market introduction.

In recent years,the microorganisms residues in endoscopes have frequently resulted in cross transmis-sion or even the outbreak of hospital-associated infections.It is of great importance to carry out standardized bio-logical surveillance of endoscopes,find out the high-risk links of cleaning and disinfection,and take targeted inter-vention measures to reduce the incidence of endoscopy-related infection.Based on the related guidelines in China and abroad as well as the latest clinical practice researches,the biological surveillance sampling and culture for en-doscopes were summarized in the article so as to enhance the surveillance quality,ensure the reprocessing effect and guarantee the endoscopy-related quality and safety.

The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

Objective:To analyze the breast cancer-related parameters and the ultrasonic features of positive axillary lymph nodes,to discuss the risk factors for axillary lymphnode metastatic burden,and to provide basis for preoperative evaluation of breast cancer patients.Methods:The ultrasonic and clinicopathological data of 574 breast cancer patients with axillary lymph node metastasis confirmed by surgery and pathology were retrospectively analyzed.According to the status of axillary lymphnode metastasis,the patients were divided into low nodal burden(LNB)group(n=283)and high nodal burden(HNB)group(n=291).The affected side,tumor quadrant,distance to skin,maximum diameter,internal echogenicity,shape,margin,calcification,blood supply,posterior echo,lymphnode long diameter,lymphnode short diameter,lymphnode aspect ratio,number of suspicious metastases,intranodal blood supply,lymphnode hilum morphology,age,pathological type,histological grade,molecular subtype,and the expressions of estrogen receptor(ER),progesterone receptor(PR),Ki-67,human epidermal growth factor receptor 2(HER2),and P53 were compared between two groups.Logistic regression was used to analyze the risk factors for axillary lymph node metastatic burden in the breast cancer patients;receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate the predictive value.Results:The univariate analysis results showed that there were statistically significant differences in tumor quadrant,distance to skin,molecular subtype,HER2 positive expression,lymphnode long diameter,lymph node short diameter,lymph node aspect ratio,number of suspicious metastases,and lymphnode hilum morphology between two groups(P<0.05).The multivariate Logistic regression analysis results showed that tumor located in the upper outer quadrant(OR=0.648,P=0.021),distance to skin<5 mm(OR=0.283,P=0.016),Luminal A(OR=1.564,P=0.044),lymphnode long diameter≥20 mm(OR=2.050,P<0.01),lymphnode short diameter≥8.6 mm(OR=2.430,P<0.01),lymph node aspect ratio<2(OR=1.585,P<0.01),and indistinct lymphnode hilum structure(OR=2.092,P<0.01)were the independent risk factors for axillary lymphnode metastatic burden.The ROC curve analysis results showed that compared with the ultrasonic features of positive axillary lymph nodes,the AUC of the combination of breast cancer-related parameters and ultrasonic features of positive axillary lymphnodes was larger(Z=2.72,P=0.006 5),and it had higher predictive value for axillary lymphnode metastatic burden.Conclusion:The tumor quadrant,distance to skin,molecular subtype,lymphnode long diameter,lymph node short diameter,lymphnode aspect ratio,and lymphnode hilum structure are the independent risk factors for axillary lymphnode metastatic burden,and they have certain predictive value for axillary lymphnode metastatic burden.

Objective To investigate the occurrence status quo and influencing factors of low muscle mass(LMM)among young and middle-aged health examination population.Methods The young and middle-aged people undergoing the body composition analysis in this hospital from January to December 2023 were selected as the study subjects.The general data,body composition indices and biochemical indicators were col-lected.The body composition analysis was performed by the bioelectrical impedance analysis(BIA).LMM was diagnosed based on the skeletal muscle index.The univariate and multivariate logistic regression were used to analyze the influencing factors of LMN occurrence in the young and middle-aged health examination population.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were em-ployed to evaluate the predictive value of each indicator.Results A total of 2 351 people undergoing the phys-ical examination were included,aged 18-49 years old,366(15.57％)cases of LMM were detected out.The skeletal muscle index,sex,age,age group distribution,body mass index(BMI),body fat percentage(BFP),body fat percentage grade,visceral fat area(VFA),AST/ALT,Hb,serum creatinine,blood uric acid,HbA1c,fasting blood glucose,TC,LDL-C,HDL-C,TG and triglyceride-glucose index(TyG)had statistical differences between the LMM group and normal group(P＜0.05).Multivariate logistic regression revealed that the sex(OR=2.606,95％CI:1.755-3.870),BMI(OR=0.579,95％CI:0.538-0.623),BFP(OR=5.885,95％CI:4.176-8.292)and VFA(OR=0.955,95％CI:0.944-0.967)were the influencing factors for the LMM oc-currence in the young and middle-aged people undergoing the physical examination(P＜0.001).The ROC a-nalysis showed the AUC values of the sex,BMI,BFP and VFA for predicting LMM were 0.580,0.821,0.636 and 0.715 respectively,in which the predictive value of BMI was highest.Conclusion The population of fe-male,low BMI,high BFP and low VFA maybe the high-risk groups for LMM.The health management for the above-mentioned groups needs to be strengthened.

Objective To analyze the mutation status of Kirsten rat sarcoma viral oncogene homolog(KRAS),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),v-raf murine sarcoma viral oncogene homolog B1(BRAF)genes,and the expression of mismatch repair(MMR)and human epidermal growth factor receptor 2(HER-2)proteins in tumor tissues of patients with colorectal cancer(CRC)harboring neuroblastoma rat sarcoma viral oncogene homolog(NRAS)gene mutations,and explore their relationships with the clinicopathological characteristics of CRC patients.Methods The clinicopathological data of 546 patients with NRAS mutation CRC were retrospectively analyzed.The mutation status of NRAS,KRAS,PIK3CA,and BRAF genes was detected by AmoyDx amplification refractory mutation system(ARMS)-polymerase chain reaction(PCR)kit(fluorescent PCR method),the expression levels of MMR and HER-2 proteins were detected by immunohistochemical staining EnVision method,and the relationship between them and the clinicopathological characteristics of patients were analyzed.Results The mutation rate of single-point mutations in the NRAS gene was 98.35%(537/546),double-point mutations in the NRAS gene were 1.65%(9/546),and double mutations in the NRAS and KRAS genes were 1.47%(8/546).No patients were found to harbor mutations in the PIK3CA or BRAF genes.The types of NRAS mutations included Q61R(or Q61K,Q61L,Q61H)mutations(266/546,48.72%),G12D(or G12S)mutations(154/546,28.21%),G13R(or G12C,G12V,G12A,G13V)mutations(134/546,24.54%),and A146T mutation(1/546,0.18%).G13R(or G12C,G12V,G12A,G13V)mutations in the NRAS gene were more likely to occur in the rectum cancer patients(P=0.035);although the tumors had a larger diameter(P=0.029),the patients had a longer progression-free survival after surgery(P=0.028).Among patients with NRAS gene mutations,HER-2 positive expression was associated with perineural invasion(P=0.003),and the patients with deficient MMR were younger on average(P=0.041)and were associated with double-point mutations in the NRAS gene(P=0.018).Conclusion CRC harboring NRAS mutations may have unique clinicopathological characteristics and molecular phenotypes,providing possibilities for individualized treatment and prognosis evaluation of CRC.

Objective To investigate the effects of cinnamic aldehyde(CA)on Bcl-2-associated X protein(Bax)and Bcl-2 homologous antagonist/killer(Bak)in vascular endothelial cells of diabetic ulcer wound tissues,as well as on cell apoptosis.Methods ① Forty-eight healthy SPF-grade male SD rats(5 weeks old,weighing 180～220 g)were randomly assigned to a control group(12 rats)and a diabetes group(36 rats).The diabetic model was established with an intraperitoneal injection of 50 mg/kg STZ-citrate sodium solution and high-fat diet feeding.The diabetes group was further randomly divided into Model group,CA group,and the rb-bFGF group,with 12 animals in each group.Wounds in the Con and Model groups were disinfected and topically treated with normal saline,CA group received topical application of 4 μmol/L CA in PEG 400 gel,and those of the rb-bFGF group were treated with bevacizumab gel.The wound healing rate of each group was calculated at 3,7 and 14 d after intervention.At 14 d after intervention,pathological changes in the wounds were observed with HE staining,and the expression levels of Bax and Bak were detected by Western blotting.② Human umbilical vein endothelial cell line EA.hy926 was treated with 175 mmol/L glucose for 48 h to establish a cell model of high glucose injury.The experimental cells were divided into control group,model group and CA treatment group.Cell scratch test and tube formation test were performed respectively to determine the migration ability and angiogenesis of the cells.The expression levels of Bax and Bak was detected with immunofluorescence assay,and cell apoptosis was detected by TUNEL staining.Results ①The diabetic rats in the Model group exhibited significantly higher blood glucose level(P<0.05),declined wound healing rate at 7 and 14 d after intervention(P<0.05),and enhanced expression levels of Bax and Bak(P<0.05)when compared with the control group.Pathological observation revealed that,at 14 d after intervention,accompanied with inflammatory reactions,dense infiltration of inflammatory cells,fewer new blood vessels,and continuous fluid exudation in the wound were observed in the Model group,but the control group presented complete epithelialization in full-thickness skin.Compared with the conditions in the Model group,both CA and rb-bFGF treatment improved the epithelialization process,with mature granulation tissues,showing good healing condition,promoted wound healing rate(P<0.05),and decreased the expression levels of Bax and Bak(P<0.05).② The results of cell experiments showed that the cells of the model group showed significantly reduced migration ability and tube formation ability(P<0.05),reduced protein levels of Bax and Bak(P<0.05),and lower apoptotic rate(P<0.05)when compared with the cells in the model group.Conclusion CA can inhibit the expression of apoptosis-related proteins Bax and Bak,promote the migration and tube formation of vascular endothelial cells,and inhibit the cell apoptosis under high glucose condition,which may be an important reason for its promoting wound healing in diabetic ulcer rats.

Objective To evaluate the clinical efficacy of acupuncture combined with Modified Zuojin Granules in treating reflux esophagitis(RE)with liver-stomach disharmony syndrome.Methods A total of 100 patients diagnosed with liver-stomach disharmony syndrome RE were enrolled from October 2022 to October 2024 at Zigong First People's Hospital.The patients were randomly assigned to the observation group and the control group,with 50 cases in each group.The control group was treated with Modified Zuojin Granules,while the observation group was given acupuncture plus Modified Zuojin Granules,both group were treated for 4 weeks.The changes in the traditional Chinese medicine(TCM)syndrome scores,24-hour esophageal acid reflux parameters(frequency and longest duration),serum gastrointestinal hormones[gastrin(GAS),motilin(MTL),vasoactive intestinal peptide(VIP)],gut microbiota composition(Lactobacillus,Bifidobacterium,Enterococcus,Enterobacter)were observed.The adverse reactions and safety profiles were evaluated.Results(1)Both groups showed significant improvement in TCM syndrome scores(P＜0.05),with greater improvement in the observation group,and the differences were statistically significant(P＜0.05).(2)After treatment,both groups of patients showed significant improvements in the number of gastric reflux episodes in the oesophagus over 24 hours and the longest reflux duration(P＜0.05).The observation group demonstrated significantly better improvements in the number of gastric reflux episodes in the oesophagus over 24 hours and the longest reflux duration compared to the control group,with statistically significant differences(P＜0.05).(3)After treatment,the serum levels of GAS,MTL,and VIP in both groups of patients were significantly improved(P＜0.05).The observation group showed significantly better improvement in serum GAS,MTL,and VIP levels compared to the control group,with statistically significant differences(P＜0.05).(4)After treatment,the levels of Lactobacilli and Bifidobacteria in both groups increased significantly compared to before treatment(P＜0.05),while the levels of Enterococci and Enterobacteria were significantly decreased(P＜0.05).The improvement in intestinal microbiota levels was more pronounced in the observation group,with statistically significant differences(P＜0.05).(5)The overall efficacy rate was 96.00％(48/50)in the observation group and 80.00％(40/50)in the control group.The observation group demonstrated superior efficacy compared to the control group,with statistically significant differences(P＜0.05).(6)The incidence of adverse reactions in the observation group was 8.00％(4/50),while that in the control group was 12.00％(6/50).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The combined therapy significantly improves clinical symptoms,modulates gastrointestinal hormones and gut microbiota,demonstrating excellent efficacy and safety for liver-stomach disharmony syndrome RE.