The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen ; Castration ; Prostatic Neoplasms, Castration-Resistant/drug therapy*

Objective: To investigate the evolution and clinical significance of HER2 low expression status in HER2 negative patients in primary and recurrent/metastatic breast cancers. Methods: The data and archived sections of 259 breast cancer patients with recurrence/metastasis and HER2-negative primary foci were collected from January 2015 to January 2022 at the Fourth Hospital of Hebei Medical University, and the HER2 status of primary and recurrence/metastasis foci was determined by immunohistochemistry (IHC), among which IHC 2+patients were subject to fluorescence in situ hybridization (FISH). The HER2 status was classified as HER2-0 group; patients with IHC 1+, IHC 2+and no FISH amplification were classified as HER2 low expression group; and patients with IHC 3+, IHC 2+and FISH amplified were classified as HER2-positive group. The changes of HER2 status in patients with HER2 low expression in primary versus recurrent/metastatic breast cancer foci were compared, and their clinicopathologic characteristics and prognosis were analyzed. Results: The overall concordance rate between primary and recurrent/metastatic HER2 status in breast cancer was 60.6% (157/259, κ=0.178). A total of 102 patients (102/259, 39.4%) had inconsistent primary and recurrent/metastatic HER2 status; 37 patients (37/259, 14.3%) had HER2-0 at the primary foci and HER2-low expression at the recurrent/metastatic; and 56 patients (56/259, 21.6%) had HER2-low expression in the primary foci and HER2-0 in the recurrent/metastatic. The recurrent/metastatic foci became low-expressing compared with the recurrent/metastatic foci which remained HER2-0 patients, with longer overall survival time, higher ER and PR positivity, lower Ki-67 positivity index, and lower tumor histological grade; all with statistically significant differences (all P<0.05). In the primary HER2-low group, patients with recurrent/metastatic foci became HER2-0 while those with recurrent/metastatic foci remained low expression; there were no statistically significant differences in clinicopathological features and overall survival time (all P>0.05). Conclusions: Unstable HER2 status in patients with HER2-0 and low expression in primary versus recurrent/metastatic breast cancer foci, and HER2-0 in the primary foci but low HER2 expression status in recurrence/metastasis is associated with favourable prognosis, and testing HER2 status in recurrence/metastasis can provide more treatment options for such patients.
Humans ; Breast Neoplasms/genetics* ; Clinical Relevance ; In Situ Hybridization, Fluorescence ; Female

Adult ; Humans ; Stomach ; Histiocytosis, Langerhans-Cell/diagnosis*

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.
Androgen Antagonists/adverse effects* ; Exanthema/chemically induced* ; Far East ; Humans ; Male ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Thiohydantoins/adverse effects*

India is a parliamentary republic country located in South Asian. Its medical and healthcare insurance is paid by the state government and it has the world’s largest "free medical" service system. India has a long history of traditional medicine (TM) represented mainly by Ayurveda, Naturopathy, Yoga etc. As early as the 2nd century BC, Traditional Chinese Medicine (TCM) was introduced to India along with religious exchanges and trade activities. At present, acupuncture has achieved independent legal status in India and there are many acupuncture clinics and associations. However, non-acupuncture TCM treatments lack development in India, but the application of acupuncture lacks of systematic standards.

Objective: To understand the characteristics on major strain subtypes of hepatitis C virus among HIV/HCV co-infected patients, so as to explore the molecular transmission clusters and related risk factors of HCV strains. Methods: A total of 336 newly reported HIV-infected patients were diagnosed as HIV/HCV co-infection in Dehong Dai and Jingpo autonomous prefecture (Dehong) in 2016. We used Nested PCR to amplify CE1 and NS5B genes among 318 samples with plasma levels above 200 μl, before using the combining phylogenetic tree and constructing molecular propagation network method to analyze the related data. Results: A total of 267 HIV/HCV co-infection patients who had met the HCV genotyping requirements were screened the gene subtypes were diversified. Among these genotypes, proportions of 3b, 6n, 6u, 1a, 3a and other subtypes appeared as 32.6% (87/267), 18.4% (49/267), 15.7%(42/267), 13.1%(35/267), 11.2%(30/267) and 9.0%(24/267) respectively. Molecular transmission network of five major HCV genotypes was constructed with a clustering rate of 39.1% (95/243). The clustering rate of subtype 1a was the highest, as 71.4% (25/35). Results from the multivariate logistic regression showed that ethnic minorities other than the Yi and Jingpo (vs. the Han, OR=0.17, 95%CI: 0.04-0.71), the married spouses (vs. the unmarried, OR=0.42, 95%CI: 0.18-0.94), the 6n and 3a subtype (vs. the 3b subtype, OR=0.34, 95%CI: 0.12-0.95; OR=0.22, 95%CI: 0.05-0.93) were more difficult to form transmission clusters. However, the 6u and 1a subtype (vs. the 3b subtype, OR=3.10, 95%CI: 1.21-7.94; OR=4.00, 95%CI: 1.32-12.11) seemed more likely to form the transmission clusters. Conclusion: Ethnicity, marital status and genetic subtypes were factors significantly associated with the formation of transmission clusters related to the major HCV gene subtypes among newly reported HIV/HCV co-infection in Dehong.
AIDS-Related Opportunistic Infections/virology* ; Asian People ; China/epidemiology* ; Coinfection ; Genotype ; HIV Infections/virology* ; Hepacivirus/isolation & purification* ; Hepatitis C/virology* ; Humans ; Phylogeny ; Polymerase Chain Reaction

[Abstract] Objective: To study the effects of ursolic acid cooperated with gemcitabine on proliferation and apoptosis of pancreatic cancer PANC-1 cells. Methods: Human pancreatic cancer cell line PANC-1 was cultured in vitro with ursolic acid and gemcitabine respectively; and MTT assay was used to determine the IC50 of ursolic acid and gemcitabine, thus obtaining the best drug concentration. Ursolic acid (2 µmol/L) and gemcitabine (0.2 µmol/L) alone or in combination was used to treat PANC-1 cells; trypan blue assay was used to test cell viability, and PI staining was used to examine the cell apoptosis; wound healing was used to detect the proliferation and migration of PANC-1 cells. The protein expressions of P-JNK, Bcl-2, IL-6, P-Stat 3, NF-κB and Cox-2 in cells of each treatment group were detected using Western blotting. Results: Both ursolic acid and gemcitabine could significantly inhibit the proliferation of PANC-1 cells, and the IC50 is 13.67 and 2.78 µmol/L, respectively; and the final concentrations were determined at 2 and 0.2 µmol/L for ursolic acid and gemcitabine, respectively. Compared with single drug treatment, the combined treatment exerted a more prominent cell proliferation inhibition effect ([46.47±5.07]% vs [78.38±8.65]%, [76.12±3.23]%, all P<0.05), apoptosis-induction effect ([39.78± 7.01]% vs [20.35±8.51]%, [20.35±8.51]%, all P<0.01) and migration inhibition effect (P<0.01) on PANC-1 cells. Western blotting showed that the combined treatment strongly inhibited Bcl-2 and IL-6 expression, accelerated P-JNK protein expression compared with single drug treatment. Conclusion: The synergistic effect of ursolic acid and gemcitabine enhanced the inhibition on proliferation, migration, and promoted cell apoptosis of human pancreatic cancer cell line PANC-1, the mechanism may be associated with inhibition of Bcl-2, Il-6, P-stat 3 proteins and promotion of P-JNK protein.

The overall details of causality frames in the objective world remain obscure, which poses difficulty for causality research. Based on the temporality of cause and effect, the objective world is divided into three time zones and two time points, in which the causal relationships of the variables are parsed by using Directed Acyclic Graphs (DAGs). Causal DAGs of the world (or causal web) is composed of two parts. One is basic or core to the whole DAGs, formed by the combination of any one variable originating from each time unit mentioned above. Cause effect is affected by the confounding only. The other is an internal DAGs within each time unit representing a parent-child or ancestor-descendant relationship, which exhibits a structure similar to the confounding. This paper summarizes the construction of causality frames for objective world research (causal DAGs), and clarify a structural basis for the control of the confounding in effect estimate.
Causality ; Computer Graphics ; Confounding Factors, Epidemiologic ; Data Interpretation, Statistical ; Epidemiologic Methods ; Humans

Objective: To understand the prevalence of alcohol drinking in 20-79 years old males with different educational backgrounds and smoking behaviors in different areas of China. Methods: A multi-stage cluster random sampling survey was conducted in 150 surveillance sites in 2010-2012 Chinese nutrition and health surveillance in China. At least 1 000 subjects were selected in each surveillance site. Alcohol drinking prevalence and pattern information were collected by using personal health and food frequency questionnaire in face to face interviews. Results: A total of 60 791 males aged 20-79 years were surveyed. The prevalence of alcohol drinking was 57.8% (58.3% in rural area, 57.3% in urban area). The mean daily alcohol intake level was 32.7 g (33.3 g in rural area, 32.1 g in urban area). The rate of almost drinking every day and daily alcohol intake level were highest among males aged 50-59 years. Mean daily alcohol intake level, rate of almost drinking every day and excessive drinking decreased with the increase of education level. Non-smokers had higher rate of never drinking and lower prevalence of drinking and excessive drinking, lower mean daily alcohol intake level, and lower rate of almost drinking every day compared with current and past smokers. Conclusions: Alcohol drinking was common in males aged 20-79 years in China, and, the difference was not obvious between rural residents and urban residents. The differences in daily intake level of different alcohol drinks among males with different characteristics had certain significance. Significant difference in excessive drinking was found among different age groups, those with different education levels and those with different smoking history.
Adult ; Aged ; Alcohol Drinking/epidemiology* ; Asian People ; China/epidemiology* ; Cross-Sectional Studies ; Humans ; Male ; Middle Aged ; Prevalence ; Rural Population ; Smoking/epidemiology* ; Socioeconomic Factors ; Surveys and Questionnaires

Objective: To understand the prevalence of biomass fuel exposure in women aged ≥40 years in China during 2014-2015, and provide evidence for the prevention and control of bio-fuel exposure. Methods: All participants were selected from a national representative cross-sectional survey during 2014-2015 in the mainland of China. A multi-stage stratified cluster sampling strategy was used. A total of 37 795 women aged ≥40 years received a face-to-face questionnaire survey at 125 surveillance points in 31 provinces. The level of biomass fuel exposure was analyzed after complex sample weighting to represent the overall Chinese women aged ≥40 years. Results: A total of 37 777 women were included in the analysis. With complex weighting, the rate of biomass fuel exposure in Chinese women aged ≥40 years was 35.8% (95%CI: 29.6%-42.1%), the exposure rate was higher in rural women than in urban women (P<0.001). The biomass fuel exposure rate was highest in northeastern and lowest in northern areas of China (χ(2)=17.03, P=0.009). The estimated biomass fuel exposure rate decreased with the increase of educational level (P<0.001). Conclusion: The prevalence of biomass fuel exposure is high in women aged ≥40 years in China, especially in those in rural areas. The exposure level differs with age and area. Appropriate measures should be taken to reduce the level of biomass fuel exposure in Chinese women.
Adult ; Aged ; Air Pollutants/toxicity* ; Air Pollution, Indoor/statistics & numerical data* ; Asian People ; Biomass ; China/epidemiology* ; Cooking/methods* ; Cross-Sectional Studies ; Female ; Fossil Fuels/toxicity* ; Humans ; Inhalation Exposure/statistics & numerical data* ; Middle Aged ; Prevalence ; Risk Factors ; Rural Population ; Surveys and Questionnaires