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 investigate follow-up participation situation, negative conversion, and tuberculosis incidence among boarding junior and senior high school freshmen with latent tuberculosis infection(LTBI) in Zhuhai, so as to provide a reference for better LTBI management in school settings. Methods: A prospective cohort study enrolled 413 LTBI and 27 184 non LTBI boarding junior and senior high school freshmen in Zhuhai from September to October 2023. The LTBI group underwent follow up retesting at >3-6, >6-12, >12-24, >24 months after screening. The followup content included mycobacterium tuberculosis infection testing,chest X ray examination,and questionaire survey(basic demographic information, lifestyle, history of close contact with tuberculosis, and suspected symptoms of pulmonary tuberculosis). Follow-up participation, negative conversion, and tuberculosis incidence were analyzed. Rate was compared by using the Chi-square test, and factors associated with negative conversion were assessed by multivariate Logistic regression analysis. Results: Follow-up participation rates increased initially and then declined, with rates of 25.67% within >3-6 months, 37.05% within >6-12 months, 82.02% within >12-24 months, and 52.21% after 24 months. The overall negative conversion rate was 61.03%. The differences in the conversion rate to negative of mycobacterium tuberculosis infection detection among junior and senior high school freshmen in the LTBI group by different testing methods, school types, smoking history, sleep status, and academic stress were all statistically significant( χ 2=124.96, 22.70, 4.71, 6.31, 6.08, all P <0.05). Multivariate Logistic regression analysis identified testing methods, smoking history, and sleep status as factors associated with negative conversion ( OR =1.90-21.67, all P <0.05). The cumulative incidence of tuberculosis was 726.39 per 100 000 in the LTBI group versus 14.71 per 100 000 in the non-LTBI group ( RR =49.37, 95% CI =11.08-219.87, P <0.01). Conclusions Boarding junior and senior high school freshmen with LTBI in Zhuhai have a higher risk of tuberculosis than concurrent non-LTBI students; they therefore represent a priority group for tuberculosis prevention and control. Centralized follow up is recommended to improve participation, and high specificity methods should be used in follow up retesting and maintain consistency across assessments.

Objective To explore the influencing factors of depression risk in elderly patients with hypertension and construct and validate a nomogram prediction model.Methods A total of 869 elderly patients with hypertension were selected from national survey database of the China Health and Retirement Longitudinal Study(CHARLS)in 2018.Multivariate Logistic regression analysis was used to identify the risk factors for depression in elderly patients with hypertension,and a nomogram prediction model was constructed.The accuracy and effectiveness of the model were validated by the Hosmer-Lemeshow(H-L)goodness-of-fit test,the area under the curve(AUC)of the receiver oper-ating characteristic(ROC)curve,and the calibration curve.Results The incidence of depression in elderly patients with hypertension was 47.18％.Factors influencing the risk of depression included rural residence(OR=2.191,P＜0.05),impaired basic activities of daily living(BADL)(OR=2.338,P＜0.05),impaired instrumental activitiesofdaily living(IADL)(OR=1.674,P＜0.05),poor life satisfaction(OR=7.348,P＜0.05),fair self-rated health(OR=0.441,P＜0.05),good self-rated health(OR=0.259,P＜0.05),and sleep duration of 6 to 9 hours(OR=0.510,P＜0.05).The AUC of the ROC curve was 0.795,the slope of the calibration curve was close to 1,and the H-L goodness-of-fit test yielded x2=5.074.The validation set showed an AUC of 0.703.Conclusion The prediction model established in this study has high accuracy and discriminative ability.Healthcare professionals can take effective preventive measures based on individual patient factors.

Objective To analyze the influencing factors and prognosis of failed initial invasive mechani-cal ventilation weaning in extremely premature infants.Methods A retrospective analysis was conducted on the clinical data of 143 extremely premature infants who were delivered at Jiangxi Maternal and Child Health Hospital and treated in the neonatal intensive care unit(NICU)from July 2021 to June 2024 and received in-vasive mechanical ventilation within 72 hours after birth.According to whether re-intubation was required within 72 hours after the initial weaning,they were divided into the successful weaning group(n=110)and the failed weaning group(n=33).Stepwise logistic regression was used to analyze the influencing factors and prognosis of failed initial invasive mechanical ventilation weaning.Results There were statistically significant differences between the two groups with different gestational ages at birth,birth weights,tracheal intubation in the delivery room or operating room,abnormal C reactive protein at admission,fraction of inspiration O2(FiO2)at admission,gestational age before weaning from the ventilator,weight before weaning from the vent-ilator,patent ductus arteriosus(PDA,≥2.5 mm),proportion of≥3 tracheal intubation times,invasive me-chanical ventilation time,oxygen supply time,and hospitalization expenses(P<0.05).The results of multiva-riate logistic regression analysis showed that gestational age at birth,abnormal C reactive protein at admis-sion,FiO2 at admission,gestational age before weaning from the ventilator,PDA(≥2.5 mm),duration of in-vasive mechanical ventilation,pulmonary hemorrhage,feeding intolerance,time to total enteral feeding,shock,and length of hospital stay were independent influencing factors for failed initial invasive mechanical ventila-tion weaning(P<0.05).Conclusion Early prevention and early treatment of risk factors are the keys to the successful weaning of extremely premature infants.

Objective:To examine the postoperative morphological changes in outer retinal wave-like changes (ORC) in eyes with rhegmatogenous retinal detachment (RRD).Methods:A retrospective clinical study. From March 2020 to March 2024, 64 eyes of 64 RRD patients diagnosed at The Second Affiliated Hospital of Zunyi Medical University were included. The cohort included 39 males (39 eyes) and 25 females (25 eyes), with a mean age of (45.3±15.7) years and a mean retinal detachment duration of (16.6±13.5) days. Macular involvement was observed in 51 eyes. Scleral buckling surgery (SB), pars plana vitrectomy (PPV), and SB+PPV were performed in 17, 44, and 3 eyes respectively. Best corrected visual acuity (BCVA) and spectral domain optical coherence tomography examinations were performed in all affected eyes. BCVA examination was performed using the standard logarithmic visual acuity chart, and the visual acuity was converted to logarithm of the minimum angle of resolution (logMAR) during statistics. Combined with the ORC situation before the operation, the morphological repositioning of outer retinal folds (ORF) after the operation was classified into types Ⅰ, Ⅱ and Ⅲ. One week and one and three months after the operation, relevant examinations were performed using the same equipment and methods as before the operation. The structural characteristics of ORC and the morphology of ORF after surgery were observed. The comparison between groups was conducted using the independent sample t test or the Mann-Whitney U test. Results:Among the 64 eyes, preoperative ORC was present in 46 eyes (71.9%, 46/64) and absent in 18 eyes (28.1%, 18/64). The 18 eyes without ORC had retinal detachment durations of either ≤4 days or ≥42 days. Postoperatively, ORF was observed in 51 eyes (79.7%, 51/64) and absent in 13 eyes (20.3%, 13/64). Among the 51 eyes with macular holes involved, 24 eyes (47.1%, 24/51) had ORF after the operation and 27 eyes (52.9%, 27/51) had no ORF. Among the 46 and 18 eyes with and without ORC, the ORF after surgery was 28 (60.9%, 28/46) and 1 (5.6%, 1/18) eyes, respectively. There was a statistically significant difference in the reduction rate of ORF after surgery between eyes with and without ORC ( χ2=15.974, P<0.001). Among the 46 eyes with ORC, the proportions of ORF to types Ⅰ, Ⅱ and Ⅲ after surgery were 24 (52.2%, 24/46), 20 (43.5%, 20/46), and 2 (4.3%, 2/46) eyes, respectively. There was no statistically significant difference in the incidence of ORF after different surgical methods in eyes with ORC ( P>0.05). One week and one month after the surgery, the logMAR BCVA of the affected eyes with and without ORF was 0.97±0.47, 0.69±0.34 and 0.85±0.32, 0.54±0.21, respectively. The BCVA of those without ORF was better than that of those with ORF, but the differences were not statistically significant ( t=0.237, 0.408; P>0.05). Conclusions:The occurrence of ORC in RRD eyes has a certain relationship with the time of retinal detachment. For RRD eyes with ORC before the operation, the repositioning morphology after the operation is more likely to show changes in ORF. The transformation from ORC to ORF after ORC surgery has no correlation with the surgical method.

Objective:To examine the postoperative morphological changes in outer retinal wave-like changes (ORC) in eyes with rhegmatogenous retinal detachment (RRD).Methods:A retrospective clinical study. From March 2020 to March 2024, 64 eyes of 64 RRD patients diagnosed at The Second Affiliated Hospital of Zunyi Medical University were included. The cohort included 39 males (39 eyes) and 25 females (25 eyes), with a mean age of (45.3±15.7) years and a mean retinal detachment duration of (16.6±13.5) days. Macular involvement was observed in 51 eyes. Scleral buckling surgery (SB), pars plana vitrectomy (PPV), and SB+PPV were performed in 17, 44, and 3 eyes respectively. Best corrected visual acuity (BCVA) and spectral domain optical coherence tomography examinations were performed in all affected eyes. BCVA examination was performed using the standard logarithmic visual acuity chart, and the visual acuity was converted to logarithm of the minimum angle of resolution (logMAR) during statistics. Combined with the ORC situation before the operation, the morphological repositioning of outer retinal folds (ORF) after the operation was classified into types Ⅰ, Ⅱ and Ⅲ. One week and one and three months after the operation, relevant examinations were performed using the same equipment and methods as before the operation. The structural characteristics of ORC and the morphology of ORF after surgery were observed. The comparison between groups was conducted using the independent sample t test or the Mann-Whitney U test. Results:Among the 64 eyes, preoperative ORC was present in 46 eyes (71.9%, 46/64) and absent in 18 eyes (28.1%, 18/64). The 18 eyes without ORC had retinal detachment durations of either ≤4 days or ≥42 days. Postoperatively, ORF was observed in 51 eyes (79.7%, 51/64) and absent in 13 eyes (20.3%, 13/64). Among the 51 eyes with macular holes involved, 24 eyes (47.1%, 24/51) had ORF after the operation and 27 eyes (52.9%, 27/51) had no ORF. Among the 46 and 18 eyes with and without ORC, the ORF after surgery was 28 (60.9%, 28/46) and 1 (5.6%, 1/18) eyes, respectively. There was a statistically significant difference in the reduction rate of ORF after surgery between eyes with and without ORC ( χ2=15.974, P<0.001). Among the 46 eyes with ORC, the proportions of ORF to types Ⅰ, Ⅱ and Ⅲ after surgery were 24 (52.2%, 24/46), 20 (43.5%, 20/46), and 2 (4.3%, 2/46) eyes, respectively. There was no statistically significant difference in the incidence of ORF after different surgical methods in eyes with ORC ( P>0.05). One week and one month after the surgery, the logMAR BCVA of the affected eyes with and without ORF was 0.97±0.47, 0.69±0.34 and 0.85±0.32, 0.54±0.21, respectively. The BCVA of those without ORF was better than that of those with ORF, but the differences were not statistically significant ( t=0.237, 0.408; P>0.05). Conclusions:The occurrence of ORC in RRD eyes has a certain relationship with the time of retinal detachment. For RRD eyes with ORC before the operation, the repositioning morphology after the operation is more likely to show changes in ORF. The transformation from ORC to ORF after ORC surgery has no correlation with the surgical method.

Objective To investigate the role of caspase-1-medicated canonical pyroptosis pathway in chlorogenic acid(CGA)treatment of acute kidney injury(AKI)in mice.Method Twenty-four C57Bl/6J mice were randomized into sham-operated group,cecal ligation and puncture(CLP)group,CLP+dexamethasone group(CLP+DXM group),and CLP+CGA group(n=6)and subjected to either sham operation(laparotomy only)or CLP.After modeling the mice received intravenous infusion of 10 mg/kg normal saline(in sham and CLP groups),1 μg/kg dexamethasone or 15 mg/kg of chlorogenic acid for 6 h delivered using an intravenous pump.Eight hours after the infusion,renal morphology and histology,renal cell apoptosis,and the renal function parameters such as urea nitrogen(BUN),creatinine(Scr),and kidney injury molecule 1(KIM-1)were compared among the 4 groups;the 7-day survival rates of the mice were recorded,and the expressions of NLRP3 inflammasomes and key proteins of the caspase-1 pathway in the renal tissue were detected.Results CGA treatment significantly improved the 7-day survival rate,reduced renal pathologies of the septic mice(P<0.05),and lowered the levels of BUN,Scr,KIM-1,NLRP3 inflammasome and expressions of key proteins of the caspase-1 pathway.Conclusion CGA alleviates AKI in mice with CLP-induced sepsis by inhibiting NLRP3 inflammasomes and the caspase-1 signaling pathway.

Objective:To construct a microfluidic organ-on-a-chip and evaluate its capability in simulating subchondral bone remodeling during the progression of osteoarthritis.Methods:The chip′s main body was designed based on the microfluidic technology and cell co-culture technique. MC3T3-E1 cells were cultured adherently within the cell seeding micro-chamber, with the culture medium perfused at a flow rate of 0.5 ml/min at the bottom of the micro-chamber. Evaluation metrics were as follows: (1) Assessment of the microfluidic organ-on-a-chip: The growth culture medium was perfused and simulation experiments were conducted to test the concentration differences and equilibrium times of the fluid inside and at the bottom of the cell seeding micro-chamber at various time points; live-dead staining was performed to observe the biocompatibility of cells cultured continuously for 3 days and 7 days at a set flow rate, which was divided into 3-day and 7-day groups. (2) Osteogenic potential of the microfluidic organ-on-a-chip: The osteogenic induction medium was perfused, and ALP staining and PCR were performed to compare the number of the black alkaline phosphatase (ALP)-positive cells and the expression levels of osteogenesis-related marker genes including osteoblast-specific transcription factor 2 (RUNX2), type I collagen (COL1A1), bone morphogenetic protein-2 (BMP-2), and osteocalcin (OCN) under static, 3-day and 7-day perfusion conditions, which was divided into static non-induced, static-induced and perfusion-induced groups. (3) Characterization of morphology and size, and biocompatibility of extracellular vesicles (EVs) of three osteoblast subtypes: Three different subtypes of osteoblasts were obtained [endothelial-type osteoblasts (EnOB)-EVs, stromal-type osteoblasts (StOB)-EVs and mineralizing-type osteoblasts (MinOB)-EVs]. Their morphology and size were obtained through transmission electron microscopy and particle size analysis. Growth medium containing EVs of three different cell subtypes was perfused, and cell proliferation/apoptosis assay was performed to compare the biocompatibility of the addition of different EVs concentrations (1, 1.25, 2.5, and 5 μg/ml) for 24 hours, which was categorized into the EnOB-EVs group, StOB-EVs group and MinOB-EVs group. (4) Osteogenic effect of EVs from three subtypes of osteoblasts: Osteogenic induction media containing EVs from three different osteoblast subtypes were perfused for 3 days, and ALP staining and PCR were performed to compare the number of black ALP-positive cells and the expression levels of osteogenesis-related marker genes including RUNX2, COL1A1, BMP-2, and OCN, which was divided into non-EVs group, EnOB-EVs group, StOB-EVs group and MinOB-EVs group.Results:(1) Evaluation of the microfluidic organ-on-a-chip: Simulation results showed that the concentration in the top layer of the upper chamber reached more than 95% of that in the lower chamber and that the concentration in the bottom layer was about 96.5% of that in the lower chamber after 12 hours of continuous perfusion, reaching an equilibrium state of the concentration difference between the upper and lower chambers. The results of live-dead staining showed that the chip was biocompatible at a flow rate of 0.5 ml/min, and the cell survival rate at 3 and 7 days of perfusion was (99.48±0.12)% and (97.07±1.05)% ( P<0.01). (2) ALP staining results showed that at 3 days, the perfusion-induced group showed the highest number of black ALP-positive cells, followed by the static-induced group, and the least in the static non-induced group. At 7 days, the static-induced group had the highest number of black ALP-positive cells, followed by the perfusion-induced group, and the least in the static non-induced group. PCR results indicated that at 3 days, the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.12, 1.00±0.01, and 1.00±0.02 respectively in the static non-induced group; 1.80±0.04, 4.05±0.37, 9.80±1.94, and 4.38±0.89 respectively in the static-induced group, and 2.45±0.23, 5.48±0.42, 91.50±4.56, and 10.82±4.96 respectively in the perfusion-induced group ( P<0.01). At 7 days, the expression levels of RUNX2 was 1.00±0.01 in the static non-induced group, 1.46±0.46 in the static-induced group, and 1.11±0.08 in the perfusion-induced group ( P>0.05); the expression levels of COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.13, and 1.00±0.09 respectively in the static non-induced group, 9.38±0.25, 14.27±4.35, and 84.01±4.02 respectviely in the static-induced group, and 2.39±0.08, 133.64±8.87, and 86.64±8.36 respectively in the perfusion-induced group ( P<0.01). When comparing the static non-induced, static-induced, and perfusion-induced groups at both 3 and 7 days, the perfusion-induced group demonstrated the strongest osteogenic capability. (3) Characterization of morphology and size and biocompatibility of EVs from three osteoblast subtypes: Under the transmission electron microscope, EVs from EnOB-EVs, StOB-EVs, and MinOB-EVs all exhibited a typical saucer-shaped morphology. The particle sizes of EnOB-EVs, StOB-EVs, and MinOB-EVs were (91.3±14.7)nm, (106.0±16.0)nm, and (68.1±10.7)nm, respectively. Cell proliferation/apoptosis assay results indicated that the optimal administration concentration of EnOB-EVs, StOB-EVs, and MinOB-EVs was all 1.25 μg/mL. (4) Validation of osteogenic effect of the microfluidic organ-on-a-chip on three types of EVs: ALP staining results showed that the non-EVs group had the fewest black ALP-positive cells, followed by the EnOB-EVs group, then the StOB-EVs group, and the MinOB-EVs group had the most. PCR results showed that the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.01, 1.00±0.03, 1.00±0.02, and 1.00±0.02 respectively in the non-EVs group, 1.95±0.11, 6.78±2.04, 7.99±0.57, and 6.93±3.83 repectively in the EnOB-EVs group, 0.79±0.12, 5.68±1.53, 12.59±3.15, and 25.59±0.95 respectively in the StOB-EVs group, and 0.68±0.10, 4.36±0.69, 18.75±3.21, and 34.74±3.98 repectively in the MinOB-EVs group ( P<0.01). Compared with the non-EVs group, EnOB-EVs group, StOB-EVs group, and MinOB-EVs group, the MinOB-EVs group showed the most significant osteogenic effect. Conclusions:The microfluidic organ-on-a-chip constructed using microfluidic technology and cell co-culture techniques is capable of maintaining the normal growth of MC3T3-E1 cells, enhancing their proliferation and osteogenic induction differentiation. EVs released by osteoblasts at different stages possess osteogenic effects and can accelerate the bone sclerosis in the remodeling of subchondral bone during the progression of osteoarthritis.

Objective To investigate the role of caspase-1-medicated canonical pyroptosis pathway in chlorogenic acid(CGA)treatment of acute kidney injury(AKI)in mice.Method Twenty-four C57Bl/6J mice were randomized into sham-operated group,cecal ligation and puncture(CLP)group,CLP+dexamethasone group(CLP+DXM group),and CLP+CGA group(n=6)and subjected to either sham operation(laparotomy only)or CLP.After modeling the mice received intravenous infusion of 10 mg/kg normal saline(in sham and CLP groups),1 μg/kg dexamethasone or 15 mg/kg of chlorogenic acid for 6 h delivered using an intravenous pump.Eight hours after the infusion,renal morphology and histology,renal cell apoptosis,and the renal function parameters such as urea nitrogen(BUN),creatinine(Scr),and kidney injury molecule 1(KIM-1)were compared among the 4 groups;the 7-day survival rates of the mice were recorded,and the expressions of NLRP3 inflammasomes and key proteins of the caspase-1 pathway in the renal tissue were detected.Results CGA treatment significantly improved the 7-day survival rate,reduced renal pathologies of the septic mice(P<0.05),and lowered the levels of BUN,Scr,KIM-1,NLRP3 inflammasome and expressions of key proteins of the caspase-1 pathway.Conclusion CGA alleviates AKI in mice with CLP-induced sepsis by inhibiting NLRP3 inflammasomes and the caspase-1 signaling pathway.

Skin avulsion injuries of the lower leg are common in clinical practice, which can easily lead to skin necrosis and infection of the lower leg, and have a significant impact on the appearance and function of the lower limb. Among them, the open avulsion injury has the highest incidence and is often accompanied by multiple tissue injuries. Therefore, improper diagnosis and treatment may cause skin and soft tissue defects of the lower leg combined with bone exposure or even bone defects, seriously impairing patients′ life and health. In order to have a better understanding of the open skin avulsion injury of the lower leg, achieve precise diagnosis and treatment and improve prognosis, the Chinese Society of Traumatology of Chinese Medical Association and the Chinese Association of Microsurgeons of Chinese Medical Doctor Association organized experts in the related fields to formulate Clinical guideline for the diagnosis and treatment of open skin avulsion injuries of the lower leg ( version 2024) based on evidence-based medicine principles. A total of 16 recommendations were proposed on the diagnosis, treatment, postoperative rehabilitation of open lower leg skin avulsion injury, so as to provide a reference for its diagnosis and treatment.