OBJECTIVE: To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. METHODS: A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. RESULTS: Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). CONCLUSION THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals ; Diabetic Cardiomyopathies/physiopathology* ; Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Myocardium/metabolism* ; Fibrosis ; Male ; Capsules ; Hypoglycemic Agents/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Rats ; Diabetes Mellitus, Experimental/drug therapy*

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

【Objective】 To investigate the current state of infant responsive caregiving and to analyze its correlation with caregiver parenting confidence, in order to provide theoretical basis for improving the level of responsive care for infants and young children. 【Methods】 A cross-sectional survey was conducted from October 2022 to February 2023 to select 1 028 infants and young children under 3 years old who underwent health examinations in the Department of Child Healthcare. Participants completed a general data questionnaire, the Karitane Parenting Confidence Scale, and the Infant Responsive Caregiving Scale. Hierarchical multiple linear regression analysis was used to investigate the related influencing factors of infant responsive care and to analyze the relationship between caregiver parenting confidence and responsive caregiving. 【Results】 The level of responsive caregiving was found to be associated with various factors such as infant age(χ²=21.196), mode of pregnancy(Z=-2.072), history of pregnancy protection during pregnancy(Z=-4.713), history of pregnancy complications (Z=-4.504), gestational week at birth(χ²=41.358), small for term infants(Z=-3.497), neonatal intracranial hemorrhage(Z=-5.425), neonatal hyperbilirubinemia(Z=-2.184), maternal education level(χ²=9.419), family income(χ²=11.211) as well as type of family (χ²=15.360)(P < 0.05). Additionally, a significant correlation was observed between parenting confidence and responsive caregiving(r=0.421,P<0.001). Hierarchical multiple linear regression analysis revealed that caregiver parenting confidence had a significant positive effect on the level of responsive caregiving (B=0.623, P<0.05), even after controlling for the effect of demographic factors. 【Conclusion】 The level of infant responsive caregiving is influenced by caregiver parenting confidence, and increasing caregiver parenting confidence can effectively improve the quality of responsive caregiving for infants and young children.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective: To explore the diagnostic value of p16/Ki-67 double-stained immunohistochemistry in the diagnosis of human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma(opscc) and find out the optimal index to improve the accuracy of HPV detection. Methods: A total of 153 cases, from May 2014 to May 2020, diagnosed OPSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, were selected. This cohort included 130 males and 23 females, aged (58.6±10.0) years old. HPV RNA in situ hybridization was chosen as the gold standard to detect their HPV status. p16 immunohistochemistry and p16/Ki-67 double-stained immunohistochemistry were performed on all cases, and the p16/Ki-67 double positive index including 20%, 40%, and 60% were used as the thresholds to compare their sensitivity, specificity, and positive prediction value (PPV), negative prediction value (NPV) and prognosis prediction ability. Results: Among the 153 patients with OPSCC, 114 were HPV-negative and 39 were HPV-positive, and the HPV infection rate of OPSCC patients was 25.5% (39/153). Only 58.1% (36/62) of single p16 positive cases were HPV-positive, and the prognosis of patients could not be distinguished using p16 immunohistochemistry only. Using p16/Ki-67 double staining, the accuracy of HPV positive diagnosis has been improved. The HPV diagnostic ability was the highest when the p16/Ki-67 double positive index was 40% (sensitivity=86.8%, specificity=94.8%, PPV=84.6%, NPV=95.6%, area under the curve=0.897), which could distinguish the prognosis of patients (P=0.012). Conclusions: The p16/Ki-67 double-stained immunohistochemistry can improve the accuracy of HPV positive diagnosis rate and diagnosis of HPV-positive oropharyngeal cancer is the most accurate when the double-positive index is 40% as the threshold to judge HPV status and could serve as better surrogate marker for HPV detection.

Objective:To analyze the clinical significance of multigene assay in papillary thyroid carcinoma（PTC）. Methods:Patients who underwent thyroidectomy in a tertiary hospital from August 2021 to May 2022 were enrolled. The eight-gene panel was used to detect the tumor tissue of patients, and the correlation between gene mutations and clinical features was analyzed. Results:Among 161 patients, mutation rate of BRAF V600E, RET/PTC1 and TERT promotor were 82.0%, 6.8% and 4.3%, respectively. BRAF V600E mutation was more common in male patients（P=0.023）. TERT promotor-mutated tumors had a large diameter（P=0.019）, a high proportion of multifocal lesions（P=0.050）, and a large number of lymph node metastases（P=0.031）. Among 89 patients who completed preoperative BRAF detection, there was a strong consistency between the preoperative aspiration test and postoperative panel（Cohen κ=0.694, 95%CI: 0.482-0.906, P<0.01）. In the hematoxylin-eosin sections obtained from 80 patients, BRAF V600E was still the main type of gene mutation, and the classical/follicular type was more distributed. TERT promotor and RET/PTC1 mutation were the main genetic events for tall-cell/columnar/hobnail type and diffuse sclerosing type, respectively. One-way ANOVA showed that there were differences in diagnosis age（P=0.029） and tumor size（P<0.01） among different pathological types. Conclusion:As a simple and feasible clinical detection method for PTC, the multigene assay can supplement the identification of important genetic events other than BRAF V600E, and provide more prognostic information and follow-up hints for postoperative patients.
Humans ; Male ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/pathology* ; Proto-Oncogene Proteins B-raf/genetics* ; Clinical Relevance ; Carcinoma, Papillary/pathology* ; Mutation

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*