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.

Objective To investigate the predictive value of multimodal magnetic resonance imaging(MRI)in the progression of transient ischemic attack(TIA)patients.Methods A retrospective study was conducted on 103 TIA patients admitted to the First Affiliated Hospital of Kangda College,Nanjing Medical University(Lianyungang First People's Hospital)from September 2021 to December 2023.These patients were divided into the TIA group(34 cases)and the ACI group(69 cases)based on whether they progressed to acute cerebral infarction(ACI).All patients underwent multimodal magnetic resonance examinations after admission.The imaging results of the cranial T1WI,T2WI,DWI,TOF-MRA,high-resolution magnetic resonance imaging,and magnetic resonance imaging perfusion-weighted imaging[plaque burden,stenosis degree,enhancement index,pial collateral grading,cerebral blood flow(CBF),cerebral blood volume(CBV),mean transit time(MTT),and time to peak(TTP)]were compared between the two groups.The correlation between multimodal MRI findings and ACI risk,as well as their predictive value for ACI,were analyzed.Additionally,multimodal MRI results were compared among patients with different degrees of neurological deficits and different prognoses.Results The ACI group exhibited higher plaque load,stenosis degree,enhancement index,MTT and TTP,worse pIA collateral grade,and lower CBF and CBV compared to the TIA group(P<0.05).Logistic regression analysis revealed that plaque burden,stenosis degree,enhancement index,MTT,and TTP were associated risk factors for disease progression in TIA patients(OR value>1,P<0.001),while pial collateral grade,CBF,and CBV were associated protective factors for disease progression in TIA patients(OR value<1,P<0.001).ROC curve showed that the AUC of ACI predicted by combination of plaque load,stenosis degree,enhancement index,MTT,TTP,pia collateral grade,CBF and CBV was 0.914(95%CI:0.842～0.960),which was greater than that of pia collateral grade alone(Z=0.314,P<0.05).Bootstrap internal validation showed that the joint prediction results were well aligned with the ideal curve,indicating that the predicted incidence of ACI was consistent with the actual incidence.The plaque load,stenosis degree,enhancement index,MTT and TTP of patients with severe neurological deficits were higher than those with mild to moderate deficits,and CBF and CBV were lower than those of mild to moderate patients(P<0.05).The plaque load,stenosis degree,enhancement index,MTT and TTP of patients with poor prognosis were highe,and CBF and CBV were lower than those of with good prognosis(P<0.05).Conclusion Multimodal MRI has certain predictive value for the disease progression in TIA patients,providing a reference for clinical assessment of the condition and prognosis prediction,and helping to formulate targeted follow-up intervention plans.

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.

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.

Objective:To investigate the effect of inspiratory muscle training on diaphragm morphology and function in ventilator induced diaphragmatic dysfunction(VIDD)rats,and to explore the mechanism of it.Method:Twenty-four adult female SD rats were randomly divided into 4 groups:①Control group(n=6);②Me-chanical ventilation group(n=6):mechanical ventilation for 24 hours;③Sham training group(n=6):spontane-ous breathing for 1 hour after mechanical ventilation for 24 hours;④Training group(n=6):intermittent inspi-ratory muscle training for 1 hour after mechanical ventilation for 24 hours.Multi-channel physiology signal col-lection and processing system were used to detect the peak twitch tension and peak tetanic force of dia-phragm,as well as the frequency-force effect curve.The cross-sectional area(CSA)of diaphragm was ob-served by hematoxylin and eosin staining method.Western-blot was used to detect the level of microtubule-as-sociated protein 1 light chain 3(LC3)and muscle atrophy F-box(MAFbx).The levels of αII-spectrin break-down products(SBDPs)SBDP145 and SBDP120 in the diaphragm were detected by ELISA.The level of malondialdehyde(MDA)in the diaphragm was detected by thiobarbituric acid(TBA)method.Result:Compared with control group and training group,the peak twitch tension,peak tetanic force and fre-quency-force effect curve of diaphragm in ventilation group and sham training group were decreased significant-ly(P<0.05),but there was no difference between the ventilation group and the sham training group or be-tween the control group and the training group.Compared with the control group,the diaphragm fiber cross-sectional area of ventilation group,sham training group or training group was significantly decreased(P<0.05),and there was no significant difference between the ventilation group and the sham training group.Compared with the ventilation group and the sham training group,the diaphragm fiber cross-sectional area of training group was increased(P<0.05).Compared with the control group,the level of MDA,SBDP120 and LC3II/I ratio in the diaphragm of ventilation group,sham training group and training group were significantly in-creased(P<0.05),and there was no difference between the ventilation group,the sham training group and the training group.Compared with the control group,the expression of MAFbx in ventilation group was signif-icantly increased(P<0.05),and there was no difference between the ventilation group,the sham training group and the training group.Compared with the control group and the training group,SBDP145 level in the diaphragm of ventilation group or sham training group was significantly increased(P<0.05),but there was no difference between the ventilation group and the sham training group.There was no difference in SBDP145 lev-el of diaphragm between the control group and the training group.Conclusion:Inspiratory muscle training can improve the morphology and function of VIDD diaphragm,and the mechanism may be related to the decrease of calpain activity.

Objective:To investigate the application value of changes in T/QRS ratio (?T/QRS) in predicting risk stratification for high-risk non-ST-elevation myocardial infarction (NSTEMI).Methods:A total of 158 patients with NSTEMI who received treatment at the Department of Cardiology, Baoji High-tech Hospital, from February 2022 to February 2024 were included in this study. Based on the global registry of acute coronary events score, the enrolled patients with NSTEMI were divided into low-, medium-, and high-risk groups. Baseline data and clinical examination results were collected for all patients, and the clinical outcomes of patients with NSTEMI in different risk stratification groups were compared and analyzed. Spearman correlation analysis was performed to assess the correlation between ?T/QRS and the global registry of acute coronary events score in patients with NSTEMI. Logistic regression analysis was conducted to identify risk factors that influence the severity of NSTEMI. The predictive value of ?T/QRS for high-risk NSTEMI in patients was evaluated using the receiver operating characteristic curve.Results:In patients with NSTEMI from the low-risk, medium-risk, and high-risk groups, the values of ?T/QRS in the inferior and lateral leads increased sequentially [(1.01 ± 0.25) vs. (1.32 ± 0.19) vs. (1.74 ± 0.21), F = 6.10, P < 0.001; (1.01 ± 0.13) vs. (1.36 ± 0.11) vs. (1.66 ± 0.05), F = 5.73, P < 0.001]. Spearman correlation analysis demonstrated a positive correlation between ?T/QRS in the inferior and lateral leads and the global registry of acute coronary events score in patients with NSTEMI ( r = 0.73, P < 0.001; r = 0.78, P < 0.001). Logistic regression analysis revealed that elevated ?T/QRS values in the inferior and lateral leads were risk factors for high-risk NSTEMI, with odds ratios of 10.361 and 10.738, respectively. Receiver operating characteristic curve analysis indicated that the area under the curve for predicting high-risk NSTEMI patients using ?T/QRS in the inferior and lateral leads was 0.932 and 0.855, respectively. Conclusions:?T/QRS in the inferior and lateral leads are associated with risk stratification in patients with NSTEMI and can effectively predict high-risk NSTEMI, suggesting a promising clinical application.

Objective:To investigate the relationship between macrophage activation related factors and clini-cal symptoms of schizophrenia(SCZ).Methods:Outpatient or inpatient SCZ patients(n=166)and normal con-trols(n=71)meeting the diagnostic criteria of DSM 4th edition were selected as subjects.The psychopathological symptoms were assessed by the Positive and Negative Syndrome Scale(PANSS),and the concentrations of α-Na-Galases,MAF and IL-18 were determined by enzyme-linked immunosorbent assay(ELISA).The correlation be-tween biological indicators and clinical symptoms was analyzed and the mediation effect was tested.Results:The concentrations of α-NaGalases(P＜0.001)and MAF(P＜0.01)in SCZ group were lower than those in normal control group.In SCZ group,IL-18 was negatively correlated with α-NaGalases concentration(r=-0.24,P＜0.01).α-NaGalases was positively correlated with MAF concentration(r=0.67,P＜0.001),and the total score of PANSS positive symptom scale was positively correlated with IL-18(r=0.21,P＜0.05)and MAF concentration(r=0.22,P＜0.01).The mediating effect of α-NaGalases and MAF was statistically significant,and the relative mediating effect accounted for 25.47％.Conclusion:The increase of IL-18 level may indicate the occurrence of positive symptoms of schizophrenia,and α-NaGalases and MAF may negatively regulate the inflammatory damage effect of IL-18 on SCZ,thereby reducing the positive symptoms.