ObjectiveTo investigate the predictive factors for HBsAg clearance in chronic hepatitis B （CHB） patients with a low level of hepatitis B surface antigen （HBsAg） treated with pegylated interferon α-2b （PEG-IFN-α-2b）， to establish a combined predictive model and a nomogram based on multiple factors， and to provide a reference for formulating individualized treatment regimens and predicting treatment outcome in clinical practice. MethodsA retrospective analysis was performed for 167 CHB patients with HBsAg <1 500 IU/mL who attended The Third People’s Hospital of Kunming from January 2022 to January 2024 and were treated with PEG-IFN-α-2b. According to whether clinical cure was achieved， the patients were divided into HBsAg clearance group and HBsAg non-clearance group. Related data were collected， including general information and serological/biochemical/virological indicators at different time points during treatment. The independent samples t-test was used for comparison of normally distributed continuous data， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data； the chi-square test was used for comparison of categorical data. The multivariate logistic regression analysis was used to identify independent influencing factors. The receiver operating characteristic （ROC） curve was used to assess the value of indicators used alone or in combination in predicting clinical cure， and calibration curves were plotted to assess the risk prediction model. ResultsThe univariate analysis showed that there were significant differences between the two groups in age （t=-6.839， P<0.05）， history of nucleos（t）ide analogue treatment for over 1 year （χ²=59.339， P<0.05）， genotype （χ²=4.610， P<0.05）， nonalcoholic fatty liver disease （χ²=5.319， P<0.05）， hepatitis B virus DNA status before treatment （χ²=60.861， P <0.05）， compensated liver cirrhosis （χ²=10.960， P<0.05）， HBeAg status before treatment （χ²=19.060， P<0.05）， a history of interferon treatment （χ²=8.162， P<0.05）， presence of interferon antibodies after treatment （χ²=12.858， P<0.05）， HBsAg level before treatment （Z=-7.412， P<0.05）， alanine aminotransaminase （ALT） level at baseline （Z=-6.117， P<0.05）， ALT level at 12 weeks of treatment （Z=-7.171， P<0.05）， platelet count （PLT） at 24 weeks of treatment （Z=-3.622， P<0.05）， and thyroid stimulating hormone （TSH） level at 24 weeks of treatment （Z=-2.830， P<0.05）. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.230， P=0.007）， history of nucleos（t）ide analogue treatment for over 1 year （OR=0.008， P=0.011）， HBeAg status before treatment （OR=0.003， P=0.012）， HBsAg level before treatment （OR=1.005， P=0.014）， ALT level at baseline （OR=0.949， P=0.014）， ALT level at 12 weeks of treatment （OR=0.969， P=0.016）， PLT at 24 weeks of treatment （OR=0.969， P=0.022）， and TSH level at 24 weeks of treatment （OR=3.608， P=0.045） were independent influencing factors for HBsAg clearance at 48 weeks of treatment in CHB patients with HBsAg <1 500 IU/mL. The Hosmer-Lemeshow goodness-of-fit test yielded χ²=1.398， P=0.994， indicating that the model had good fitting. The Bootstrap method was used to perform internal validation of the nomogram model， and there was a good degree of fitting between the calibration curve and the ideal curve， with a mean absolute error of 0.029. The ROC curve analysis showed that the combination of predictive factors had an area under the ROC curve of 0.982 （95% confidence interval： 0.961 — 0.999）， with a sensitivity of 94.10% and a specificity of 93.10%， suggesting that the nomogram model had a good discriminatory ability. For the CHB patients with HBsAg <1 500 IU/mL and different features， further analysis of HBsAg clearance rate at 48 weeks of treatment showed an HBsAg clearance rate of 69.60% for those with HBsAg ≤67.65 IU/mL before treatment， 58.30% for those with a baseline ALT level of ≥62.50 U/L， 68.30% for those with an ALT level of ≥92.50 U/L at 12 weeks of treatment， 42.40% for those with PLT ≥104×10⁹/L at 24 weeks of treatment， and 48.30% for those with a TSH level of ≤1.38 μIU/mL at 24 weeks of treatment， with significant differences between the two groups （all P<0.001）. ConclusionAge， history of nucleos（t）ide analogue treatment for over 1 year， HBeAg status before treatment， HBsAg level before treatment， baseline ALT level， ALT level at 12 weeks of treatment， PLT level at 24 weeks， and TSH level at 24 weeks of treatment are independent predictive factors. The combined prediction nomogram model constructed in this study has a relatively high value in predicting clinical cure at 48 weeks of PEG-IFN-α-2b treatment in CHB patients with HBsAg<1 500 IU/mL， thereby providing a reference for selecting suitable treatment population and predicting clinical cure.

Objective:To investigate the surgical effect of total parathyroidectomy combined with calf subcutaneous autotransplantation in the treatment of secondary hyperparathyroidism.Method:From Dec 2018 to Dec 2022,31 patients with secondary hyperparathyroidism who underwent total parathyroidectomy combined with calf subcutaneous autotransplantation in our hospital were selected to analyze the therapeutic effect.Results:All 31 operations were successfully completed.A total of 120 parathyroid glands were removed,including 27 cases(87.10%)with 4 parathyroid glands and 4 cases(12.90%)with 3 parathyroid glands.The average length of hospitalization was(15.82±8.74)days.Compared with preoperative parathyroid hormone,the value of parathyroid hormone decreased by more than 50%after 20 min of total parathyroidectomy.The levels of serum calcium,phosphorus,iPTH and calcium-phosphorus product at each time point after operation were significantly lower than those before operation(P＜0.01).The symptoms of joint pain was significantly improved in all patients after operation.During the postoperative follow-up of 31 patients,1 patient was confirmed to have graft recurrence at 6 months after operation,which was surgically removed.Conclusion:Total parathyroidectomy combined with calf subcutaneous autotransplantation can effectively treat secondary hyperparathyroidism and significantly improve the quality of life.

Objective To investigate the predictive factors for the occurrence of HBsAg clearance in patients with HBeAg-negative chronic hepatitis B(CHB)receiving peginterferon alfa-2b(PEG-IFN-α-2b)treatment,analyze the effects of various indicators on the HBsAg clearance rate under different characteristics,and construct and evaluate a combined predictive model.Methods We included 125 patients with HBeAg-negative CHB at Kunming Third People's Hospital from May 2021 to May 2023.After treatment with PEG-IFN-α-2b combined with nucleoside analogues for a course of 48 weeks,they were divided into HBsAg clearance group and HBsAg non-clearance group.Their general information and serological,biochemical,and virological indicators at different time points during treatment were recorded.Continuous data in normal distribution were compared using the t test.Continuous data in non-normal distribution were compared using the Mann-Whitney U test,and comparisons across different time points were performed using the multiple paired-sample Friedman test.Categorical data were compared using the χ2 test.A Logistic regression analysis was used to select variables to establish a combined multi-parameter predictive model.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic value of individual indicators and the combined predictive model for HBsAg clearance.Results Before treatment,there were significant differences in baseline HBsAg level(Z=-3.997,P<0.05)and treatment history(χ2=8.221,P<0.05)between the two groups.During treatment,gradually decreasing trends were observed in white blood cell count(χ2=104.944),neutrophil count(χ2=132.036),platelet count(χ2=162.881),and thyroid-stimulating hormone level(TSH,χ2=83.304,all P<0.05),while alanine aminotransferase(ALT,χ2=157.618)and alpha fetoprotein(χ2=159.472)showed gradually increasing trends(both P<0.05).At 48 weeks of treatment,treatment history(odds ratio[OR]=0.232,95%confidence interval[CI]:0.071-0.753),baseline HBsAg level(OR=13.423,95%CI:3.276-54.997),the extent of decrease in HBsAg from baseline after 12 weeks of treatment(OR=0.143,95%CI:0.040-0.515),the maximum ALT level during treatment(OR=0.986,95%CI:0.980-0.993),and the minimum TSH level during treatment(OR=3.281,95%CI:1.413-7.619)were independent factors affecting HBsAg clearance(all P<0.05).A combined predictive model for HBsAg clearance was built:Y=-1.603-1.462×treatment history+2.597×baseline HBsAg value-1.944×the extent of HBsAg reduction from baseline after 12 weeks of treatment-0.014×the maximum ALT value during treatment+1.188×the minimum TSH value during treatment.The diagnostic value of the individual indicators for HBsAg clearance from high to low was as following:the maximum ALT value during treatment(AUC=0.824),baseline HBsAg value(AUC=0.727),the minimum TSH value during treatment(AUC=0.707),the extent of HBsAg reduction from baseline after 12 weeks of treatment(AUC=0.641),and treatment history(AUC=0.636).The combined model showed better predictive performance than the individual indicators,with the AUC being 0.921(all P<0.05).Conclusion The combined model,constructed with baseline HBsAg value,the extent of HBsAg reduction from baseline after 12 weeks of treatment,the maximum ALT value during treatment,and the minimum TSH value during treatment,has high predictive value for the occurrence of HBsAg clearance in patients with HBeAg-negative CHB after 48 weeks of treatment with PEG-IFN-α-2b,which can provide a reference for identifying suitable patients for treatment and predicting clinical outcome.

Objective To investigate the predictive factors for the occurrence of HBsAg clearance in patients with HBeAg-negative chronic hepatitis B(CHB)receiving peginterferon alfa-2b(PEG-IFN-α-2b)treatment,analyze the effects of various indicators on the HBsAg clearance rate under different characteristics,and construct and evaluate a combined predictive model.Methods We included 125 patients with HBeAg-negative CHB at Kunming Third People's Hospital from May 2021 to May 2023.After treatment with PEG-IFN-α-2b combined with nucleoside analogues for a course of 48 weeks,they were divided into HBsAg clearance group and HBsAg non-clearance group.Their general information and serological,biochemical,and virological indicators at different time points during treatment were recorded.Continuous data in normal distribution were compared using the t test.Continuous data in non-normal distribution were compared using the Mann-Whitney U test,and comparisons across different time points were performed using the multiple paired-sample Friedman test.Categorical data were compared using the χ2 test.A Logistic regression analysis was used to select variables to establish a combined multi-parameter predictive model.Receiver operating characteristic(ROC)curves were generated to evaluate the diagnostic value of individual indicators and the combined predictive model for HBsAg clearance.Results Before treatment,there were significant differences in baseline HBsAg level(Z=-3.997,P<0.05)and treatment history(χ2=8.221,P<0.05)between the two groups.During treatment,gradually decreasing trends were observed in white blood cell count(χ2=104.944),neutrophil count(χ2=132.036),platelet count(χ2=162.881),and thyroid-stimulating hormone level(TSH,χ2=83.304,all P<0.05),while alanine aminotransferase(ALT,χ2=157.618)and alpha fetoprotein(χ2=159.472)showed gradually increasing trends(both P<0.05).At 48 weeks of treatment,treatment history(odds ratio[OR]=0.232,95%confidence interval[CI]:0.071-0.753),baseline HBsAg level(OR=13.423,95%CI:3.276-54.997),the extent of decrease in HBsAg from baseline after 12 weeks of treatment(OR=0.143,95%CI:0.040-0.515),the maximum ALT level during treatment(OR=0.986,95%CI:0.980-0.993),and the minimum TSH level during treatment(OR=3.281,95%CI:1.413-7.619)were independent factors affecting HBsAg clearance(all P<0.05).A combined predictive model for HBsAg clearance was built:Y=-1.603-1.462×treatment history+2.597×baseline HBsAg value-1.944×the extent of HBsAg reduction from baseline after 12 weeks of treatment-0.014×the maximum ALT value during treatment+1.188×the minimum TSH value during treatment.The diagnostic value of the individual indicators for HBsAg clearance from high to low was as following:the maximum ALT value during treatment(AUC=0.824),baseline HBsAg value(AUC=0.727),the minimum TSH value during treatment(AUC=0.707),the extent of HBsAg reduction from baseline after 12 weeks of treatment(AUC=0.641),and treatment history(AUC=0.636).The combined model showed better predictive performance than the individual indicators,with the AUC being 0.921(all P<0.05).Conclusion The combined model,constructed with baseline HBsAg value,the extent of HBsAg reduction from baseline after 12 weeks of treatment,the maximum ALT value during treatment,and the minimum TSH value during treatment,has high predictive value for the occurrence of HBsAg clearance in patients with HBeAg-negative CHB after 48 weeks of treatment with PEG-IFN-α-2b,which can provide a reference for identifying suitable patients for treatment and predicting clinical outcome.

Objective To explore the correlation between serum angiotensin-converting enzyme(SACE),matrix metalloproteinase-9(MMP-9)and haptoglobin(HPT)with pulmonary infection in patients with schizophrenia.Methods A total of 83 patients with schizophrenia were selected and divided into the infected group(40 cases)and the non-infected group(43 cases)according to whether they had pulmonary infection.Data of antipsychotic drugs,length of hospital stay,course of disease and electroconvulsive therapy were collected.Serum SACE,MMP-9 and HPT levels were detected by enzyme-linked immunosorbent assay.Spearman correlation analysis was used to determine serum SACE,MMP-9 and HPT and pulmonary infection in patients with schizophrenia.Logistic regression was used to analyze risk factors for pulmonary infection in patients with schizophrenia,and receiver operating characteristic(ROC)curves were used to evaluate the predictive value of serum SACE,MMP-9 and HPT in patients with pulmonary infection.Results Before treatment,the types of antipsychotic drugs≥2,the proportion of electroconvulsive therapy,serum SACE,MMP-9 and HPT levels were higher in the infected group than those in the non-infected group(P＜0.05).After treatment,there were no significant differences in serum SACE,MMP-9 and HPT levels between the infected group and the non-infected group(P＞0.05).Serum SACE,MMP-9 and HPT were positively correlated with pulmonary infection in patients with schizophrenia(P＜0.05).More than 2 types of antipsychotic drugs,electroconvulsive therapy and elevated SACE,MMP-9 and HPT were risk factors for pulmonary infection in schizophrenia patients(P＜0.05).The ROC curve analysis showed that the combined serum SACE,MMP-9 and HPT for pneumonia in schizophrenic patients were better than each of these indicators alone in predicting pulmonary infection in patients with schizophrenia.Conclusion Serum SACE,MMP-9 and HPT are related with pulmonary infection in patients with schizophrenia,and which can be used as potential indicators for predicting pulmonary infection in patients with schizophrenia.

Objective:To investigate the feasibility of stapled closure of the internal fistula orifice in anal fistula (SCIA) combined with catheter drainage in the extra-sphincteric space in the treatment of high complex anal fistula.Methods:Methods Surgical procedure: Under combined spinal-epidural anesthesia, a submucosal purse-string suture was placed above the dentate line, and the stapler was inserted to close the internal opening. The fistulous tract was dissected from the external opening toward the cranial side and excised along its path to the level of the levator ani muscle, followed by placement of catheter drainage in the extra-sphincteric space.Results:A retrospective analysis was conducted on the clinical data of a 40-year-old male patient with a high-position complex anal fistula, who underwent SCIA combined with catheter drainage in the extra-sphincteric space at the Department of Colorectal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine in December 2024. The surgery was successful with minimal intraoperative bleeding, a complete anastomosis, and thorough fistula tract dissection. There was no sphincter injury occurred, and the catheter drainage was unobstructed. The patient was discharged on postoperative day 8. Postoperative follow-up visits were conducted at 2 months and 6 months after surgery. The patient had no symptoms such as pain, purulent discharge, or pruritus. MRI scans of the anal canal (both plain and contrast-enhanced) at 2 months and 6 months showed no recurrence of the fistula. The Wexner fecal incontinence score was 0, indicating normal bowel control, and the Garg score was less than 8, suggesting fistula healing and low probability of recurrence.Conclusion:SCIA combined with catheter drainage in the extra-sphincteric space is a safe and feasible procedure for the treatment of high complex anal fistula.

ObjectiveTo investigate the efficacy and safety of the direct-acting antiviral agents coblopasvir hydrochloride/sofosbuvir （CLP/SOF） regimen used alone or in combination with ribavirin （RBV） in the treatment of patients with genotype 3 hepatitis C virus （HCV） infection in terms of virologic response rate， liver function recovery， improvement in liver stiffness measurement （LSM）， and adverse drug reactions， and to provide a reference for clinical medication. MethodsA total of 98 patients with genotype 3 HCV infection who attended The Third People’s Hospital of Kunming from January 2022 to December 2023 were enrolled， and according to the treatment method， the patients were divided into CLP/SOF+RBV treatment group with 55 patients and CLP/SOF treatment group with 43 patients. The patients were observed in terms of rapid virologic response at week 4 （RVR4）， sustained virologic response （SVR）， previous treatment experience， underlying diseases， laboratory and imaging indicators， and adverse reactions during treatment. The course of treatment was 12 weeks， and the patients were followed up for 12 weeks after drug withdrawal. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the Friedman test was used for comparison within each group at different time points， and the Bonferroni method was used for further comparison and correction of P value； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for SVR12. ResultsBefore treatment， there were significant differences between the CLP/SOF+RBV treatment group and the CLP/SOF treatment group in terms of LSM， total bilirubin （TBil）， gamma-glutamyl transpeptidase （GGT）， HCV genotype， and the presence or absence of liver cirrhosis and compensation （all P<0.05）. The 98 patients with genotype 3 HCV infection had an RVR4 rate of 81.6% and an SVR12 rate of 93.9%. The patients with genotype 3a HCV infection had an RVR4 rate of 84.44% and an SVR12 rate of 97.78%， while the patients with genotype 3b HCV infection had an RVR4 rate of 79.25% and an SVR12 rate of 90.57%. There were significant differences in RVR4 and SVR12 rates between the patients without hepatocellular carcinoma and those with hepatocellular carcinoma， there was a significant difference in RVR4 rate between the patients without HIV infection and those with HIV infection， and there was a significant difference in SVR12 rate between the previously untreated patients and the treatment-experienced patients （all P<0.05）. The univariate Logistic regression analysis showed that treatment history， hypertension， hepatocellular carcinoma， ascites， albumin （Alb）， and platelet count were influencing factors for SVR12 （all P<0.05）， and the multivariate Logistic regression analysis showed that hepatocellular carcinoma （odds ratio=0.034， 95% confidence interval： 0.002‍ ‍—‍‍ 0.666， P=0.026） was an independent influencing factor for SVR12. After treatment with CLP/SOF combined with RBV or CLP/SOF alone， the patients with genotype 3 HCV infection showed gradual reductions in the liver function parameters of TBil， GGT， and alanine aminotransferase （all P<0.05） and a gradual increase in the level of Alb （P<0.05）. As for renal function， there were no significant changes in blood urea nitrogen and creatinine after treatment （P>0.05）. For the patients with or without liver cirrhosis， there was a significant reduction in LSM from baseline after treatment for 12 weeks （P<0.05）. Among the 98 patients with genotype 3 HCV infection， 9 tested positive for HCV-RNA at 12 weeks after treatment， 2 showed no response during treatment， 4 showed virologic breakthrough， and 3 experienced recurrence. The overall incidence rate of adverse events during treatment was 17.35% for all patients. ConclusionCLP/SOF alone or in combination with RBV has a relatively high SVR rate in the treatment of genotype 3 HCV infection， with good tolerability and safety in patients during treatment， and therefore， it holds promise for clinical application.

ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January， 2019 to December， 2022 were enrolled， among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group， and 154 patients without recompensation were enrolled as control group. Related clinical data were collected， and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and the receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis， 63 （29.03%） had recompensation. There were significant differences between the recompensation group and the control group in HIV history （χ²=4.566， P=0.034）， history of partial splenic embolism （χ²=6.687， P=0.014）， Child-Pugh classification （χ²=11.978， P=0.003）， grade of ascites （χ²=14.229， P<0.001）， albumin （t=4.063， P<0.001）， prealbumin （Z=-3.077， P=0.002）， high-density lipoprotein （t=2.854， P=0.011）， high-sensitivity C-reactive protein （Z=-2.447， P=0.014）， prothrombin time （Z=-2.441， P=0.015）， carcinoembryonic antigen （Z=-2.113， P=0.035）， alpha-fetoprotein （AFP） （Z=-2.063， P=0.039）， CA125 （Z=-2.270， P=0.023）， TT3 （Z=-3.304， P<0.001）， TT4 （Z=-2.221， P=0.026）， CD45⁺ （Z=-2.278， P=0.023）， interleukin-5 （Z=-2.845， P=0.004）， tumor necrosis factor-α （Z=-2.176， P=0.030）， and portal vein width （Z=-5.283， P=0.005）. The multivariate analysis showed that history of partial splenic embolism （odds ratio ［OR］=3.064， P=0.049）， HIV history （OR=0.195， P=0.027）， a small amount of ascites （OR=3.390， P=0.017）， AFP （OR=1.003， P=0.004）， and portal vein width （OR=0.600， P<0.001） were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history， grade of ascites， history of partial splenic embolism， AFP， portal vein width， and the combined predictive model of these indices had an area under the ROC curve of 0.556， 0.641， 0.560， 0.589， 0.745， and 0.817， respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis， those with a history of partial splenic embolism， a small amount of ascites， and an increase in AFP level are more likely to experience recompensation， while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.

ObjectiveTo investigate the influencing factors for hepatic hydrothorax （HH） before intervention for primary hepatic carcinoma （PHC）， and to construct and assess the nomogram risk prediction model. MethodsA retrospective analysis was performed for the clinical data of 353 hospitalized patients who attended the Third People’s Hospital of Kunming for the first time from October 2012 to October 2021 and there diagnosed with PHC， and according to the presence or absence of HH， they were divided into HH group with 153 patients and non-HH group with 200 patients. General data and the data of initial clinical testing after admission were collected from all PHC patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. After the multicollinearity test was performed for the variables with statistical significance determined by the univariate analysis， the multivariate Logistic regression analysis was used to identify independent influencing factors. The “rms” software package was used to construct a nomogram risk prediction model， and the Hosmer-Lemeshow test and the receiver operating characteristic （ROC） curve were used to assess the risk prediction model； the “Calibration Curves” software package was used to plot the calibration curve， and the “rmda” software package was used to plot the clinical decision curve and the clinical impact curve. ResultsAmong the 353 patients with PHC， there were 153 patients with HH， with a prevalence rate of 43.34%. Child-Pugh class B （odds ratio ［OR］=2.652， 95% confidence interval ［CI］： 1.050 — 6.698， P=0.039）， Child-Pugh class C （OR=7.963， 95%CI： 1.046‍ ‍—‍ ‍60.632， P=0.045）， total protein （OR=0.947， 95%CI： 0.914‍ ‍—‍ ‍0.981， P=0.003）， high-sensitivity C-reactive protein （OR=1.007， 95%CI： 1.001‍ ‍—‍ ‍1.014， P=0.025）， and interleukin-2 （OR=0.801， 95%CI： 0.653‍ ‍—‍ ‍0.981， P=0.032） were independent influencing factors for HH before PHC intervention， and a nomogram risk prediction model was established based on these factors. The Hosmer-Lemeshow test showed that the model had a good degree of fitting （χ²=5.006， P=0.757）， with an area under the ROC curve of 0.752 （95%CI： 0.701‍ ‍—‍ ‍0.803）， a sensitivity of 78.40%， and a specificity of 63.50%. The calibration curve showed that the model had good consistency in predicting HH before PHC intervention， and the clinical decision curve and the clinical impact curve showed that the model had good clinical practicability within a certain threshold range. ConclusionChild-Pugh class， total protein， interleukin-2， and high-sensitivity C-reactive protein are independent influencing factors for developing HH before PHC intervention， and the nomogram model established based on these factors can effectively predict the risk of developing HH.

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins