This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

OBJECTIVE To explore the moisture and components change law of Peucedani Radix slices during microwave vacuum drying, and effectively improve the drying efficiency and slice quality of Peucedani Radix slices, by carring out drying characteristics analysis and simulation of Peucedani Radix Slices during microwave vacuum drying. METHODS Microwave vacuum drying experiments of Peucedani Radix slices under different drying conditions (microwave power density, vacuum degree and slice thickness) were carried out. The changes of moisture ratio and drying rate during drying process were studied. The contents of three coumarin ingredients (praeruptorin A, praeruptorin B and praeruptorin E) in dried Peucedani Radix slices were determined by HPLC. Weibull function was used to simulate and analyze the moisture ratio curve during drying process. RESULTS Microwave vacuum drying process of Peucedani Radix slices has three stages: acceleration, constant speed and deceleration. Compared with vacuum degree and slice thickness, increasing microwave power density could shorten drying time and improve drying efficiency more effectively. In the range of experimental parameters, the optimum drying conditions were as follows: microwave power density was 3.0 W·g–1, vacuum degree was 800 Pa, and slice thickness was 2 mm. The changes of all drying conditions had no significant effect on the content of coumarins in dried Peucedani Radix slices. The results of Weibull function simulation and analysis showed that the scale parameters under different drying conditions ranged from 17.43 to 45.38, and the smaller the value, the shorter the drying time. The shape parameters ranged from 1.41 to 1.77 and were all greater than 1, indicating that the drying process was controlled by internal and external water diffusion. CONCLUSION The research work not only provides important theoretical basis and technical support for the process improvement and quality control of microwave vacuum drying process of Peucedani Radix slices, but also provides important reference for the standardization of Peucedani Radix slices drying and the formation of quality characteristics.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

BACKGROUND: The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China. METHODS: A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1-Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups. RESULTS: The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors ( χ2 = 29.5, P <0.001). After adjustment for potential confounders, subjects with HGIs ≤-0.75 or >0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027-2.069) and 2.222 (95% CI, 1.641-3.026) compared to subjects with HGIs of >-0.75 and ≤-0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤-0.75 (OR, 1.540 [1.039-2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392-2.890]; P <0.001) compared to those with HGIs of ≤-0.75 or >0.82 after adjustment for potential confounders. CONCLUSIONS We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk.
Humans ; Cohort Studies ; Longitudinal Studies ; Diabetes Mellitus, Type 2/diagnosis* ; Maillard Reaction ; Glycated Hemoglobin ; Cardiovascular Diseases

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
Humans ; Ritonavir/therapeutic use* ; COVID-19 ; Antiviral Agents/therapeutic use* ; China ; Nitriles ; Lactams ; Proline ; Adenosine/analogs & derivatives* ; Leucine

Background: and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods: We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results: Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*

The association between serum uric acid and the risk of incident diabetes in Chinese adults remains unknown. This study aimed to investigate this association in a community-dwelling population aged ≥ 40 years in Shanghai, China. Oral glucose tole3rance test was conducted during baseline and follow-up visits. Relative risk regression was utilized to examine the associations between baseline gender-specific serum uric acid levels and incident diabetes risk. A total of 613 (10.3%) incident diabetes cases were identified during the follow-up visit after 4.5 years. Fasting plasma glucose, postload glucose, and glycated hemoglobin A1c during the follow-up visit progressively increased across the sex-specific quartiles of serum uric acid (all Ps < 0.05). The incidence rate of diabetes increased across the quartiles of serum uric acid (7.43%, 8.77%, 11.47%, and 13.43%). Multivariate adjusted regression analysis revealed that individuals in the highest quartile had 1.36-fold increased risk of diabetes compared with those in the lowest quartile of serum uric acid (odds ratio (95% confidence interval) = 1.36 (1.06-1.73)). Stratified analysis indicated that the association was only observed in women. Accordingly, serum uric acid was associated with the increased risk of incident diabetes among middle-aged and elderly Chinese women.
Adult ; Aged ; China/epidemiology* ; Diabetes Mellitus/epidemiology* ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Uric Acid

Objective: To explore the positive expressions of P16 and Ki-67 proteins in cervical biopsy lesions of patients with high-risk HPV infection and abnormal detection of liquid-based thin-layer cytology test(TCT), and the clinical value in predicting occurrence of early cervical cancer. Methods: A total of 120 patients with high-risk HPV infection(16 and 18 subtypes positive) and abnormal TCT in the Traditional Chinese Medicine Hospital of Linhai from January 2016 to July 2017 were enrolled in the study.The colposcopy was used to get cervical biopsy lesions for pathological diagnosis, immunohistochemical staining was used to detect P16 and Ki-67 proteins. Results: There were up to 66 patients with HPV-16 positive, 34 cases with HPV-18 positive, other 20 cases with 16 and 18 positive; 6 cases of atypical squamous epithelial cells(ASC), 46 cases of low-grade squamous intraepithelial lesions (LSIL), 60 cases of high-grade SIL(HSIL), other 8 cases of cervical squamous cell carcinoma(SCC) were diagnosed by TCT; 5 cases of inflammation, 105 cases of CIN and 10 cases of SCC by pathologically diagnosis.The positive rates of P16 and Ki-67 proteins were gradually increased in patients with inflammation, CIN and SCC[0(0/5), 36.2%(38/105), 70.0%(7/10), χ²=4.382, P=0.036; 0(0/5), 40.0%(42/105), 80.0%(8/10), χ²=5.945, P=0.015]. The patients with CIN were followed up for 21~36 months, median time 29.5 months.Twenty-six patients progressed to SCC, at the end of follow-up, the positive rates of P16 and Ki-67 proteins in patients with SCC were significantly higher than those in the CIN patients without progress[61.5%(16/26) vs.39.2%(31/79), χ²=3.934, P=0.047; 69.2%(18/26) vs.41.8%(33/79), χ²=5.905, P=0.015]. Conclusion The positive expression rates of P16 and Ki-67 proteins in cervical biopsy tissues are significantly higher in patients with high-risk HPV infection and abnormal TCT, which in patients with pathologically diagnosis of SCC are higher than CIN patients, the same results in CIN patients with SCC progression than non-progressing patients, suggesting that P16 and Ki-67 proteins are of great value in predicting occurrence of early cervical cancer.