Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

ObjectiveTo develop and preliminarily validate a prediction model for brace treatment failure risk in patients with adolescent idiopathic scoliosis (AIS), based on information obtained before brace treatment and during initial brace fitting. MethodsA total of 191 patients with AIS who initiated thoracolumbosacral orthosis treatment at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March, 2015 to August, 2024 and had determinable outcomes were retrospectively included. Patients were divided according to a prespecified scheme into a training set (n = 133) and a validation set (n = 58). Brace treatment failure was defined as progression of the major-curve Cobb angle by ≥ 5° from baseline during follow-up or at brace weaning, or a final major-curve Cobb angle > 45°. Logistic regression, random forest, support vector machine with radial basis function kernel, and extreme gradient boosting (XGBoost) models were developed using routinely available clinical and radiographic variables before brace treatment and during initial brace fitting. Stratified five-fold cross-validation was used for hyperparameter tuning in the training set. Model performance was evaluated in the validation set using the area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (AUPRC), Brier score, calibration curves, and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) was used to interpret the main explanatory model. ResultsIn cross-validation of the training set, both random forest and XGBoost showed good discriminative performance, with cross-validation-AUC values of 0.871 and 0.880, respectively. In the validation set, the AUC values of random forest and XGBoost were 0.888 and 0.899, the AUPRC values were 0.678 and 0.830, and the Brier scores were 0.086 and 0.076, respectively. Random forest was selected as the primary model for interpretation, with a calibration intercept of 0.091 and a calibration slope of 0.995. SHAP analysis indicated that the in-brace correction rate and the major-curve Cobb angle measured in the brace contributed most to the model predictions. ConclusionThe random forest model developed using routinely available pretreatment and initial-fitting variables shows preliminary predictive value for brace treatment failure risk in AIS, and may provide quantitative support for follow-up scheduling, brace-fit reassessment and early adherence-oriented management.

Objective:To evaluate the safety of discontinuing nucleoside/nucleoside analogue (NAs) therapy in patients with compensated hepatitis B cirrhosis after HBsAg negative conversion.Methods:A total of 3 783 patients with hepatitis B cirrhosis in compensated stage were treated with NAs at Taizhou Hospital, Taizhou Municipal Hospital and Taizhou Enze Hospital from January 2008 to December 2020. The clinical data and laboratory tests results of 85 patients with HBsAg negative conversion were retrospectively analyzed, including 36 cases discontinued the drug, and 49 continued to use drug. Chi-square test and rank-sum test were used for data analysis.Results:During the 24 and 48 months of follow-up, the ALT levels were within the normal range in both groups. There were no significant differences in positive rates of anti-HBs and HBeAg ( χ2=0.75, 0.39 and 0.90, P=0.78 0.84 and 0.34; χ2=0.40, 0.00 and 0.00, P=0.84, 1.00 and 1.00) between two groups. After 48 months of follow-up, 2 cases of primary liver cancer occurred in the discontinuation group and no primary liver cancer occurred in the continuation group ( χ2=0.89, P=0.34). Throughout the follow-up, HBsAg remained negative and HBV DNA load was below the lower limit of detection in both groups. Conclusions:Discontinuation of NAs can be considered after the HBsAg negative conversion in patients with compensated hepatitis B cirrhosis.

Objective:To investigate the relationship between the expression of hepatocyte nuclear factor-1 α (HNF-1α) and the occurrence and development of liver inflammation and fibrosis in liver tissues of patients with chronic hepatitis B.Methods:Sixty-four patients with chronic hepatitis B who were diagnosed and treated in our hospital from 2011 to 2018 were selected. All patients underwent ultrasound-guided aspiration liver biopsy. The pathological results of liver biopsy were collected for inflammation grading and fibrosis staging. The liver puncture biopsies was collected by paraffin sectioning. The expression of HNF1α in the liver tissue was detected by immunohistochemical staining. Mantel-Haenszel χ2 test was used for bidirectional ordered grouping data, and Spearman’s rank-correlation test was used for rank correlation analysis. Results:There were varying degrees of inflammatory necrosis and fibrosis in the liver tissues of patients with chronic hepatitis B. There was a linear relationship between the expression of HNF1α and the level of inflammation in liver tissues ( χ2MH = 40.70, P < 0.05). The expression of HNF1α in liver tissues of patients with chronic hepatitis B was decreased with the increase of liver inflammation. The expression intensity of HNF1α was negatively correlated with the inflammation grade ( rs = -0.815, P < 0.05). There was a linear relationship between the expressions of HNF1α and the degree and stage of liver fibrosis ( χ2MH = 31.95, P < 0.05). The expression level of HNF1α in liver tissue was gradually decreased with the aggravation of liver fibrosis. The expression intensity of HNF1α was negatively correlated with fibrosis stage ( rs = -0.713, P < 0.05). Conclusion:HNF1α is closely related to the occurrence and development of liver tissue inflammation and fibrosis, and is expected to be a sensitive indicator for evaluating the level of liver tissue inflammation and fibrosis in patients with chronic hepatitis B. In addition, its down-regulation may be involved in the process of occurrence and development of liver inflammation and liver fibrosis, and may become a new target for the treatment of chronic hepatitis B.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective To evaluate the clinical efficacy and safety of ritonavir-boosted danoprevir (DNVr) combined with daclatasvir (DCV) in the treatment of patients with genotype 1b chronic hepatitis C (CHC).Methods Thirty-three patients with genotype 1b CHC admitted in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from August 2018 to February 2019 were enrolled.All the patients received DNVr +DCV antiviral treatment.HCV RNA levels were detected before and 2, 4, 12 weeks after treatment, and after drug withdrawal , respectively.Indicators of liver and kidney function and adverse events were observed.ANOVAV of repeated measurement was used to analyze the data. Results The baseline viral loads of 33 patients ranged from 1.12×104 to 1.76×107 IU／mL.Two weeks after treatment the viral loads of all patients were down to the lowest limit of detection (＜500 IU／mL). Serum ALT, AST and TBil levels returned to norml ( F＝58.26, 14.49 and 20.16, all P＜0.05) and sustained virologic response reached 100%12 weeks after drug withdrawal.Three cases had minor adverse reactions during the treatment.Conclusion DNVr combined with DCV can achieve a rapid and strong virological response in the treatment of patients with genotype 1b CHC with good safety.

Objective To compare the difference and effectiveness between Tetra-ataxiametry and Berg balance scale (BBS) in predicting the risk for fall in the elderly inpatients.Methods A total of 401 elderly inpatients were randomly selected using convenience sampling in a class III grade A hospital. Tetra-ataxiametry and BBS were used to monitor the risk for falls of elderly patients in two groups: group with or without fall histories.Results Fall histories were set as the standard. The area ratios under receiver operating characteristic (ROC) of Tetra-ataxiametry fall index (FI) and BBS were 0.762 and 0.705. Youden index showed that the predicted value, the sensibility and the specificity of Tetra-ataxiametry FI were 41, 80.5% and 60.2%; while those for BBS were 46, 67.1% and 65.8%. No statistically significant difference in the area under the curve (AUC) between Tetra-ataxiametry and BBS was observed(P=0.0587).Conclusions There is no statistically significant difference in predicting the risk for fall in the elderly inpatients between Tetra-ataxiametry and BBS, suggesting that Tetra-ataxiametry can replace BBS to evaluate the fall risk, and is better than BBS, since Tetra-ataxiametry has higher sensitivity in objective data provision, body weight and BMI (body mass index).

Objective To investigate the effect of long-term antiviral treatment on clinical outcome and liver histology in patients with hepatitis B virus ( HBV)-related compensated cirrhosis .Methods A total of 61 patients with HBV-related compensated cirrhosis receiving antiviral therapy were enrolled from Taizhou Hospital of Zhejiang Province during September 2010 and March 2015, including 26 HBeAg-positive cases and 35 HBeAg-negative cases .Thirty-nine patients were treated with entecavir ( ETV ) and 22 were treated with adefovir dipivoxil ( ADV ) .Biochemical , serological and virological markers were examined every 3 months during treatment, and Child-Turcotte-Pugh (CTP) scores were calculated.All the patients underwent liver biopsy before and 144 weeks after antiviral treatment .Metavir scoring system was used to evaluate the liver histological activity ( A) and fibrosis score ( F) .Wilcoxon rank sum test and paired t-test were used for the evaluation of liver histopathology and liver function before and after treatment , respectively.Results After 144 weeks of antiviral treatment , HBV DNA was reduced and below the lower limit of detection in 58 patients (95.1%), HBeAg disappeared in 14 patients (14/26, 53.8%), and HBeAg seroconversion was observed in 10 patients (10/26, 38.5%); alanine aminotransferase ( ALT), aspartate amino transaminase (AST), total bilirubin (TBil) and CTP score decreased (t=7.489, 8.259, 14.000 and 6.026, all P<0.01), prothrombin time (PT) was shortened (t=9.777, P<0.01), and serum albumin (Alb) increased (t=3.446, P<0.01).Improvements in both liver histologic activity and fibrosis score were observed (Z=5.716 and 6.657, all P<0.01).Liver histological activity decreased from A1 to A0 in 16 cases, from A2 to A0 in 9 cases, from A2 to A1 in 15 cases, from A3 to A0 in 1 case, from A3 to A1 in 5 cases, and from A3 to A2 in 5 cases.Fibrosis score at the baseline was F 4 for all patients, while after treatment, there were 7 patients with F1, 22 with F2, 20 with F3, and F4 remained in rest 12 patients.Conclusion Both clinical and histological improvements can be obtained after long-term antiviral treatment for patients with HBV-related compensated cirrhosis .

ObjectiveTo explore the influence of portal vein thrombosis (PVT) on the clinical efifcacy of endoscopic esophageal variceal ligation (EVL) in cirrhotic patients with esophagogastric variceal hemorrhage (EVH).MethodsClinical data of 314 cirrhotic patients with EVH who underwent endoscopic EVL and were followed up for more than 6 months in the Third Afifliated Hospital of Sun Yat-sen University between January 2005 and December 2014 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. The patients were divided into the PVT group and the control group according to whether they had PVT during treatment. Among the 72 patients in the PVT group, 61 were males and 11 were females with the mean age of (50±11) years old.Among the 242 patients in the control group, 206 were males and 36 were females with the mean age of (47±11) years old. The clinical efifcacy of two groups was compared, and the correlation between PVT and the elimination rate of esophageal varices (EV) as well as the recurrent bleeding rate of EV was analyzed. The number of EVL treatment period in two groups was compared usingt test and the rate was compared using Chi-square test. Univariate logistic regression analysis was conducted for the correlation between PVT and the elimination rate, recurrent bleeding rate of EV.ResultsThirty-six patients in the PVT group and 115 patients in the control group developed acute EVH. After EVL, the emergency hemostatic rate of both groups was 100%. The elimination rate of EV in the PVT group was 76%(55/72), signiifcantly lower than 90%(218/242) in the control group (χ2=9.166,P<0.05). The number of EVL treatment period in the PVT group was 3.4±1.6, significantly more than 2.8±1.1 in the control group (t=3.065,P<0.05). The recurrent bleeding rate of EV in the PVT group was 36%(26/72), signiifcantly higher than 21%(51/242) in the control group (χ2=6.779,P<0.05). PVT was a risk factor for both the elimination rate of EV (OR=0.356, 95%CI: 0.179-0.709,P<0.05) and the recurrent bleeding rate of EV (OR=2.383, 95%CI: 1.354-4.196,P<0.05). ConclusionPVT is a risk factor for both the elimination rate of EV and the recurrent bleeding rate of EV in cirrhotic patients with EVH treated by endoscopic EVL.