Objective:To explore the effects of Yishen Tonglong Granules (YSTLG) on cell proliferation and apoptosis in a nude mouse model of androgen independent prostate cancer subcutaneous transplantation based on non classical Wnt signaling pathway.Methods:The tumor-bearing nude mouse model was established using the human prostate cancer bone metastatic cell line PC-3. After successful modeling, the mice were equally divided into six groups using the random number table method: model group, Western medicine group, Chinese materia medica low-, medium-, and high-dosage groups, and Chinese materia medica-Western medicine combination group. Corresponding drug interventions were administered to each group. Following 28 consecutive days of drug administration, the nude mice were euthanized. Tumor tissues were harvested for pathological observation via HE staining. Cell proliferation was assessed by immunohistochemistry; apoptosis was detected using TUNEL assay; the expressions of non-canonical Wnt signaling pathway-related proteins (Wnt5a, Rac1, RhoA, NFATc1) were analyzed through Western blot and immunohistochemical methods.Results:THE staining results demonstrated that YSTLG could effectively ameliorate pathological alterations in tumor tissues. Compared with the model group, the Chinese materia medica low-, medium-, and high-dosage groups, as well as the Chinese materia medica-Western medicine combination group, exhibited reduced proliferation indices ( P<0.01), elevated apoptosis indices ( P<0.01), down-regulated protein expressions of Wnt5a, Rac1, RhoA, and NFATc1 ( P<0.01), and decreased optical density values of Wnt5a, Rac1, RhoA, and NFATc1 ( P<0.01). These effects displayed a dosage-dependent trend. The Chinese materia medica-Western medicine combination group achieved the most pronounced therapeutic outcomes. Conclusions:YSTLG may exert inhibitory effects on the proliferation of androgen-independent prostate cancer cells and promote apoptosis, possibly through suppression of the non-canonical Wnt signaling pathway. Furthermore, its combination with Wnt signaling inhibitors may exhibit synergistic therapeutic effects.

Objective To investigate the prognosis of patients with negative sentinel lymph nodes(SLN)after neoadjuvant chemotherapy(NAC)for breast cancer who are exempt from axillary lymph node dissection(ALND)and evaluate its safety in clinical treatment.Methods Clinical data of 2,163 patients initially diagnosed with breast cancer and having negative SLNs after NAC were se-lected from the SEER database from 2018 to 2021.Among them,373 patients underwent only SLN biopsy(SLNB group),and 1,790 patients underwent ALND(ALND group).Propensity score matching(PSM)was used to control for confounding factors,and the Kaplan-Meier method was em-ployed to analyze the overall survival rate.Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors influencing the exemption from ALND in patients with negative SLNs after NAC for breast cancer.Results Before PSM,significant differences were observed be-tween the two groups in terms of clinical tumor stage,molecular subtype,estrogen receptor(ER)sta-tus,progesterone receptor(PR)status,human epidermal growth factor receptor 2(HER-2)status,efficacy of NAC,and breast surgery method(P＜0.05).After PSM,363 patients were included in each group.Univariate Cox regression analysis after PSM revealed that age,clinical tumor stage,and ER status were associated with overall survival(OS)of patients(P＜0.05).There was no sig-nificant difference in OS between patients who underwent SLNB and those who underwent ALND(P＞0.05).Multivariate Cox regression analysis indicated that age and clinical tumor stage were independent factors influencing OS in patients with negative SLNs after NAC.Survival curve analysis after PSM showed no statistically significant difference in overall survival rate between the SLNB and ALND groups(P=0.278).Conclusion Exemption from ALND in patients with negative SLNs af-ter NAC is feasible and does not affect the overall survival rate of patients.

Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Objective:To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE). Methods:Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children′s Medical Center between January 2018 and June 2022 were collected. The children were grouped based on their age of onset, clinical manifestations, neurodevelopmental status, and results of genetic testing. The correlation between SCN1A genotypes and clinical phenotypes was analyzed. Results:Among the 46 patients, 2 children (4.35%) had developed the symptoms before 3 months of age, 42 (91.30%) were between 3 to 9 months, and 2 cases (4.35%) were after 10 months. Two cases (4.35%) presented with epilepsy of infancy with migrating focal seizures (EIMFS), while 44 (95.7%) had presented with Dravet syndrome (DS), including 28 cases (63.6%) with focal onset (DS-F), 13 cases (29.5%) with myoclonic type (DS-M), 1 case (2.27%) with generalized type (DS-G), and 2 cases (4.55%) with status epilepticus type (DS-SE). Both of the two EIMFS children had severe developmental delay, and among the DS patients, 7 cases had normal development, while the remaining had developmental delay. A total of 44 variants were identified through genetic sequencing, which included 16 missense variants and 28 truncating variants. All EIMFS children had carried the c. 677C>T (p.Thr226Met) missense variant. In the DS group, there was a significant difference in the age of onset between the missense variants group and the truncating variants group ( P < 0.05). Missense variants were more common in D1 (7/15, 46.7%) and pore regions (8/15, 53.3%), while truncating variants were more common in D1 (12/28, 42.9%). Children with variants outside the pore region were more likely to develop myoclonic seizures. Conclusion:The clinical phenotypes of DEE are diverse. There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene. Missense variants outside the pore region are associated with a higher incidence of myoclonic seizures.

Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions.In the less developed regions of Asia and Africa,a high seropositivity rate has been reported for hepatitis E virus(HEV)antibodies.Although acute hepatitis E is often self-limited and has a favorable prognosis,some populations experience severe manifestations,which may progress to liver failure.Moreover,some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis.Proactive screening,reducing misdiagnosis,improving patient management,timely anti-viral therapy for severe and chronic cases,and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E.This review focused on the clinical presentation,management,and prevention of hepatitis E.

Background and aim:Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods:Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation. Results:Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained unde-tectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9％)patients with an estimated annual inci-dence of HBsAg seroclearance of 3.6％.Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of＞1000 IU/mL(33.3％vs.5.4％).The pro-portion of patients with HBsAg ≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions:Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg sero-clearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

Background and aims:Antiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).No data are available on the long-term prognosis or safety of tenofovir alafenamide(TAF),tenofovir disoproxil fumarate(TDF),or entecavir(ETV)in treating HBV-ACLF globally.This study was conducted to investigate the long-term efficacy and safety of the three nucleos(t)ide analogs in the treatment of HBV-ACLF.Methods:In this prospective,real-world cohort study,patients with HBV-ACLF were assigned to the TAF,TDF,and ETV groups.A total of 199 patients completed the 144-week follow-up.After propensity score matching(PSM),44 patients remained in each group for further analysis of survival status,incidence of hepatocellular carcinoma(HCC),virological response,and liver and renal function indicators.Results:In the original cohort,HCC developed in one patient in each group.No serious drug-related adverse events were observed.In the PSM cohort,the 144-week survival rates were 56.82％,75.00％,and 59.09％in the TAF,TDF,and ETV groups,respectively(P=0.118).When stratified into noncirrhosis and cirrhosis subgroups at baseline,the survival rate of the ETV group was slightly lower than that of the TAF and TDF group in noncirrhosis patients(P=0.338),and the survival rate of the TAF group was slightly lower than that of the TDF and ETV group in cirrhosis patients(P=0.052),but the differences were not statistically significant.The long-term overall survival rates in the TAF,TDF,and ETV groups were comparable.After 144 weeks,no significant difference in the virological response rate or liver or renal function indicators was found among the three groups,except for the level of aspartate amino-transferase,which was significantly higher in the TDF group than in the ETV group at week 144(P=0.001).Conclusions:There were no significant differences in the survival rate,incidence of HCC,efficacy or safety associated with the use of these three nucleos(t)ide analogs in treating HBV-ACLF.Trial registration:ClinicalTrials.gov NCT03920618.

Objective:To explore the feasibility of extracting the key plane of the normal fetal palate on the 11-13 + 6 week from tomography ultrasonography imaging based on artificial intelligence. Methods:The fetal volume datas of 235 cases of 11-13 + 6 week normal fetal were collected from the Department of Ultrasound in the Luohu District People′s Hospital of Shenzhen and Huazhong University of Science and Technology Union Shenzhen Hospital from May 2020 to April 2021. The data acquisition was completed by sonographers A and B by using the GE Voluson E10 color Doppler ultrasound diagnostic instrument. All datas were marked offline by sonographer C. Tomographic imaging was performed on all included data by sonographer D, the tomographic images were saved and the time-consuming was recorded, and the datas of the sonographer group were obtained. The labeled data were randomly divided into the training set and test set for model transfer learning and testing.The 4-fold cross-validation was adopted to record the test set image output by the model and the time consumption to obtain the intelligent group data. A senior sonographer performed image analysis on the two groups of data images. The feasibility of the intelligent model was verified by comparing the score of the plane of retronasal triangle(RTP), the acquisition rate of RTP, the acquisition rate of the fault, and the time-consuming difference between the sonographer group and the intelligent group. Results:①There was no significant difference in the overall distribution of RTP scores between the sonographer group and intelligent group [5 (5, 6) points vs 5 (5, 6) points, Z=0.355, P=0.722]. The RTP acquisition rate of the sonographer group and intelligent group was not statistically significant (78.72% vs 76.60%, χ 2=0.55, P=0.458). The consistency and correlation of RTP obtained by the two groups were high (Kappa=0.645, φ=0.646, both P<0.001). ②The effective layers of the sonographer group were 9 (8, 9) and the intelligent group was 8 (7, 9). The fault acquisition rate of the doctor group was higher than that of the intelligent group (78.72% vs 68.51%, χ 2=12.52, P=0.001). The consistency and correlation of the two groups in obtaining faults were media (Kappa=0.503, φ=0.521, both P<0.001). ③The time-consuming of the intelligent group was significantly lower than that of the sonographer group [1.50 (1.23, 1.75)s vs 26.94 (22.28, 30.48)s, Z=11.440, P<0.001]. Conclusions:This research model can quickly and accurately realize the extraction and tomography of the key plane of the normal fetal palate on the 11-13 + 6 week.

Objective:To report cases of multiple mitochondrial dysfunction syndrome 2 (MMDS2) caused by BOLA3 gene mutation, hoping to help clinical diagnosis. Methods:The medical records of a child with MMDS2 admitted to the Department of Neurology, Guangzhou Women and Children′s Medical Center in November 2021 were analyzed, and the clinical, imaging characteristics and prognosis of MMDS2 were summarized by literature review.Results:This 1 year and 9 months old male had a disease that started in childhood, with motor function regression and hyperlactatemia. Head magnetic resonance imaging indicated white matter lesions, and gene examination indicated the homozygous variation of BOLA3 gene c.295C>T(p.Arg99Trp). The diagnosis of MMDS2 was clear for the child. After treatment, the clinical symptoms and imaging of the child recovered significantly. Through literature review, 13 children with MMDS2 reported in 7 English literatures were reviewed. These cases had similar manifestations with the case reported in this study. Among them, 1 case recovered and 8 cases died in infancy. Conclusions:MMDS2 patients often show nervous system dysfunction such as motor regression, elevated lactate and white matter lesions, which often cause multiple system disorders. Some children die early, but some of them can be recovered.