ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

BACKGROUND:It has been found that mitochondrial function is abnormal in patients with chronic fatigue syndrome,and the administration of coenzymes can improve the symptoms.Warm acupuncture is one of the most important treatments for this disease,but its mechanism of action is unclear. OBJECTIVE:To investigate the effects of warm acupuncture on the phosphatase and tensin inducible kinase 1(PINK1)/Parkin pathway in the skeletal muscle of rats with chronic fatigue syndrome. METHODS:After 3 days of adaptive feeding,32 male Sprague-Dawley rats were randomly divided into normal control,model,warm acupuncture,and coenzyme Q groups with 8 rats in each group.The chronic fatigue syndrome model was established by multiple factors,including swimming exhaustion,chronic immobilization and fasting.After successful modeling,the normal group and the model group were treated with the same fixation and gavage procedures,and the warm acupuncture group was treated with acupuncture at Guanyuan,Zhongwan and Zusanli(bilateral)points,once a day.After the needling was inserted,the moxa pillar was put on the needle handle and ignited,three sessions once.The coenzyme Q group was given 1 mL/kg coenzyme by gavage,once a day for 14 days.The body mass,exhaustive swimming time and food utilization rate during the treatment were recorded.After the treatment,the bilateral gastrocnemius muscles of rats in each group were collected.The pathological morphology of the gastrocnemius muscle was observed by hematoxylin-eosin staining,the mitochondrial morphology and autophagosome of the gastrocnemius muscle were observed by transmission electron microscope.The expression level of microtubule-associated protein light chain 3(LC3)Ⅱ protein in the skeletal muscle was detected by immunohistochemistry.Western blot was used to detect the expression of PINK1,Parkin,LC3 Ⅰ,and LC3 Ⅱ in the skeletal muscle. RESULTS AND CONCLUSION:Compared with the normal group,the gastrocnemius muscle nuclei of the model group were pyknotic,condensed,the number of cells was increased,the cells were arranged disorderly,and the fibers in the gastrocnemius muscle were tightly arranged in the model group.Compared with the model group,the intercellular space became smaller,the nuclei were reduced,and the cell arrangement was orderly in the warm acupuncture group and coenzyme Q group.Compared with the normal group,the skeletal muscle mitochondria in the model group were swollen,fused,and vacuolated seriously,the membrane was partially broken,the matrix was more dissolved,the cristae was broken and disappeared,and autophagy appeared.Compared with the model group,the number of mitochondria increased,the arrangement was relatively neat,mitochondrial vacuolization and rupture of cristae in the gastrocnemius muscle were improved,the membrane structure was relatively intact,and autophagy occurred.Compared with the normal group,the expression of PINK1 protein in the skeletal muscle of the model group was significantly increased(P<0.05),while the expression of Parkin,LC3 Ⅱ and LC3 Ⅱ/Ⅰ protein was slightly upregulated(P>0.05).Compared with the model group,the protein expressions of PINK1,Parkin,LC3 Ⅱ and LC3 Ⅱ/Ⅰ were significantly upregulated in the warm acupuncture and coenzyme Q groups(P<0.05),and the up-regulation was more significant in the warm acupuncture group.To conclude,warm acupuncture can play a role in the treatment of chronic fatigue syndrome by activating the PINK1/Parkin pathway,upregulating LC3 Ⅱ expression,forming mitochondrial autophagosomes,promoting the degradation of damaged mitochondria,and improving mitochondrial quality.

ObjectiveTo investigate the general situation， dietary factors， and clinical features of patients with recurrent primary common bile duct stones， and to provide a basis for effective prevention of stone recurrence. MethodsA retrospective analysis was performed for 23 730 patients who underwent cholecystectomy due to cholelithiasis in Department of Hepatobiliary， Pancreatic and Spleen Surgery， Inner Mongolia People’s Hospital， from January 2013 to December 2023， and according to the presence or absence of recurrence of primary common bile duct stones after surgery， 334 patients were divided into recurrence group. The recurrence group was further analyzed based on sex in terms of recurrence rate， recurrence cycle， recurrence age， recurrence type， and general， disease， imaging， and dietary factors. The independent-samples t test was used for comparison of continuous data between two groups， the chi-square test was used for comparison of categorical data between two groups. ResultsThere were 334 cases of recurrence of primary bile duct stones after cholecystectomy， with a recurrence rate of 1.41%， and the highest frequency of recurrence cycle was observed in 10 years after surgery， with a significant difference in recurrence cycle between the male and female patients （t=5.238， P<0.001）. There was a significant difference in the recurrence rate of stones after surgery between the patients with simple gallstones and those with gallbladder and common bile duct stones at initial diagnosis （1.23% vs 2.76%， χ²=42.104， P<0.001）. The patients with recurrence aged >60 years accounted for the highest proportion in the whole population and in both male and female populations， and 92% were Han residents； 10% of the patients with recurrence had a family history of gallstones， and as for comorbidities， the patients with hypertension accounted for the highest proportion. Among the patients with recurrence， the patients with smoking or drinking accounted for 76.7% and 10.3%， respectively. As for body weight， 63.8% of the patients with recurrence had a normal body mass index （BMI）， and 23.2% of the patients were overweight； compared with body weight at the time of the first gallbladder surgery， a reduction in body weight was observed in 60.1% of the patients with recurrence， while an increase in body weight was observed in 22.9% of the patients with recurrence. There were significant differences between the male and female patients with recurrence in age composition， ethnicity， the type of place of residence， comorbidities， smoking， drinking， BMI， and the change in body weight （all P<0.001）. As for the type of stone recurrence， the ratio of multiple stones， solitary stones， and muddy stones was 74∶15∶11， and the stone size of <1 cm， 1-2 cm， and >2 cm accounted for about 40.5%， 48.8%， and 10.6%， respectively. As for the surgical procedure， the patients undergoing laparotomy accounted for 66.1%， and those undergoing laparoscopy accounted for 33.9%. The patients with various types of dyslipidemia accounted for a percentage of<30%. There were significant differences between the male and female patients with recurrence in the type of stones at initial onset， the type and size of stones， and surgical procedure （all P<0.001）. Imaging data showed that 4 patients had an abnormal structure of the bile duct， manifesting as long and curve cystic ducts， and 73.1% of the patients had common bile duct dilatation after surgery. The follow-up of dietary factors showed irregular diets in 55.8% of the patients with recurrence. As for the dietary structure， meat and staple food accounted for 43.8% and 37.8%， respectively， which showed a sex difference， with meat in male patients and staple food in female patients； 64.1% of the patients with recurrence had a high-salt and high-oil diet； 59.8% of the patients had changes in diet after the first surgery for stones， among whom 80% were able to have a regular diet， and the patients with a regular diet accounted for 92%. ConclusionThere is a relatively low recurrence rate of primary common bile duct stones in this area， and there is no sex difference. The peak of recurrence is 10 years after surgery， and recurrence of stones is mainly observed in the population aged >60 years. The analysis of dietary and clinical features can help doctors and patients to further understand the characteristics of the recurrence of primary common bile duct stones and provide a basis for subsequent targeted prevention.

AIM:This study aims to investigate the regulatory effect of the endocannabinoid 2-arachidonoyl glycerol(2-AG)on voltage-gated calcium channels(VGCCs)in caudate nucleus(CN)neurons subjected to kainic acid(KA)-induced damage,and to elucidate the underlying mechanisms involved.METHODS:Primary cultured CN neu-rons from neonatal Sprague-Dawley(SD)rats were treated with KA to establish an excitotoxic cellular model.The whole-cell patch-clamp technique was utilized to assess the effects of 2-AG on KA-induced excitotoxicity,along with the changes in the electrical properties of VGCCs.This included evaluations of current density,current-voltage relationships,and the kinetics of channel activation and inactivation.RESULTS:Treatment with KA significantly increased the current density and altered the electrical properties of VGCCs,as indicated by a reduction in the half-inactivation voltage and a shift of the inactivation curve towards depolarized potentials.Notably,KA did not affect the activation characteristics of VGCCs.Ad-ministration of exogenous 2-AG or the application of the monoacylglycerol lipase inhibitor URB602,which inhibits 2-AG degradation and elevates intracellular levels of 2-AG,effectively inhibited the KA-induced increase in VGCC current den-sity and the depolarization shift of the inactivation curve,highlighting the involvement of cannabinoid receptor 1(CB1R).CONCLUSION:The endocannabinoid 2-AG can modulate the function of VGCCs in CN neurons via the CB1R pathway,offering protective effects against excitotoxic damage induced by KA.

Objective To investigate the effect of the rs3765467 polymorphism of glucagon-like peptide-1 receptor(GLP-1R)gene on the efficacy of Liraglutide(Lir)in patients with type 2 diabetes mellitus(T2DM)and metabolic associated fatty liver disease(MAFLD).Methods A total of 281 patients with T2DM from May 2022 to May 2023 were selected,including 125 patients with simple T2DM(T2DM group)and 156 patients with T2DM combined with MAFLD(T2DM+MAFLD group).120 healthy individuals during the same period were selected as the control(NC)group.The related indexes of glucose and lipid metabolism were detected.The polymorphism of GLP-1R gene rs3765467 was detected.Results BMI,FPG,HbA1c,HOMA-IR and TG in each group increased in turn(P<0.05),while the distribution frequency of genotype GG and allele G decreased in turn(P<0.05).TC and LDL-C in T2DM and T2DM+MAFLD groups were higher than those in NC group(P<0.05).TC and TG levels in genotype GA/AA patients were significantly higher than those in genotype GG patients(P<0.05).Compared with before treatment,the levels of BMI,FPG,HbA1c,HOMA-IR,TC,TG and LDL-C in T2DM patients with MAFLD were significantly decreased after Lir treatment(P<0.05).There was no significant difference in BMI and related indexes of glucose and lipid metabolism in GG and GA/AA patients before and after Lir treatment(P>0.05).Conclusions The distribution frequency of GG and G allele at rs3765467 of GLP-1R gene is reduced in T2DM patients with MAFLD.The carrying of allele A was associated with increased TC and TG levels,but did not affect the efficacy of Lir in reducing weight and improving glycolipid metabolism.

This article reviews the benifits and challenges of nano-microspheres (NPs) in the treatment of osteoarthritis (OA). OA is a degenerative disease associated with aging, trauma, and excessive loading, with treatment strategies including basic therapy, drug therapy, reparative therapy, and reconstructive surgery. As emerging nanomaterials, NPs offer unique advantages in promoting cartilage repair due to their high surface area, excellent drug-loading capacity, and good biocompatibility. These advantages include facilitating chondrocyte generation through magnetic-mechanical control of mesenchymal stem cell microspheres and enhancing antioxidant levels using biomimetic liposomal NPs combined with glucosamine. Additionally, NPs can effectively modulate inflammatory responses, such as by inhibiting the formation of M1 macrophages and promoting their polarization to the M2 type to alleviate inflammation. Some NPs also enhance joint lubrication and relieve pain, such as hyaluronic acid-based NPs modified with choline phosphate groups. However, the application of NPs faces challenges such as high production costs, poor biocompatibility for certain types, and unknown long-term safety. Despite these challenges, with advancements in nanotechnology and a deeper understanding of the pathological mechanisms of OA, NPs are expected to provide new therapeutic approaches and more comprehensive and effective treatment options for OA patients in the future.

Objective:To analyze the prevalence and clinical characteristics of pertussis in children with different cough durations.Methods:From January 2021 to October 2022, information on children aged 0-18 years who visited eight hospitals in Shandong Province due to cough was enrolled. Pertussis serological antibody testing and/or nucleic acid testing were performed. The prevalence and clinical characteristics of pertussis were compared among the acute cough group, protracted cough group, and chronic cough group using the χ2 test or Fisher′s exact test. Results:A total of 1 565 children with cough were included in the study, of which 348 (22.24%) were laboratory-confirmed pertussis. There was a significant difference in the laboratory-confirmed rate of pertussis among different cough groups ( χ2=83.424, P<0.001). The confirmation rate of pertussis in the protracted cough group (42.21%) was significantly higher than that in the acute cough group (16.49%, P<0.05) and chronic cough group (19.50%, P<0.05). In each cough group, the age of children was significantly associated with the confirmed rate of pertussis, and the confirmed rate was relatively high in children aged 3 months to <2 years. Pertussis vaccination was significantly associated with the confirmed rate in all groups, and the confirmed rate was higher in unvaccinated children. Among laboratory-confirmed pertussis cases, the incidence of typical symptoms such as paroxysmal cough, whoop, and post-tussive emesis or sleep disturbance was significantly higher than that in the non-confirmed cases. In the protracted and chronic cough groups, the proportion of non-confirmed cases complicated with asthma/cough variant asthma (CVA) was significantly higher than that in pertussis-confirmed cases. Conclusion:There are differences in the confirmation rate of pertussis among children with different cough durations. The confirmation rate is significantly associated with age, vaccination status, and clinical symptoms. Enhancing clinical vigilance against pertussis, conducting early diagnosis, and getting timely and standardized vaccination are crucial for effectively controlling pertussis and preventing outbreaks.