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Abstract Liver fibrosis is an important pathological process in chronic liver disease and cirrhosis. Recent studies have found a close association between intestinal microbiota and the development of liver fibrosis. To determine whether there are differences in the intestinal microbiota between rhesus macaques with liver fibrosis (MG) and normal rhesus macaques (MN), fecal samples were collected from 8 male MG and 12 male MN. The biological composition of the intestinal microbiota was then detected using 16S rRNA gene sequencing. The results revealed statistically significant differences in ASVs and Chao1 in the alpha-diversity and the beta-diversity of intestinal microbiota between MG and MN. Both groups shared Prevotella and Lactobacillus as common dominant microbiota. However, beneficial bacteria such as Lactobacillus were significantly less abundant in MG (P = 0.02). Predictive functional analysis using PICRUSt2 gene prediction revealed that MG exhibited a higher relative abundance of functions related to substance transport and metabolic pathways. This study may provide insight into further exploration of the mechanisms by which intestinal microbiota affect liver fibrosis and its potential future use in treating liver fibrosis.

Abstract Purpose Patients with advanced non-small cell lung cancer (NSCLC) mostly receive essential routine care and support from informal caregivers, who usually experience poorer health-related quality of life (HRQoL). The study aimed to evaluate the HRQoL and its predictors among informal caregivers of patients with advanced NSCLC in China. Methods We interviewed the adult caregiver population of patients with advanced NSCLC (stage IIIB~IV) in nine tertiary hospitals from multiple provinces in China between November 2020 and June 2021. The EQ-5D-5L instrument measured the HRQoL of caregivers, as analyzed by employing descriptive analysis, univariate analysis, Tobit regression, and multivariate logistic regression, and investigated the important influencing factors further. Results A valid sample of 553 caregivers was analyzed. The mean EQ-5D-5L utility score of caregivers was 0.92 (SD = 0.14). Caregivers reported the greatest problems in mental health, with 45.39% reporting slight, moderate, severe, or extreme anxiety/depression. The potential influencing factors of HRQoL in caregivers included patients' age and cancer histology, relationship with the patients, and daily caregiving hours. Compared to other caregivers, patients' spouses had the lowest HRQoL. In addition, over six hours of caregiving per day was associated with lower HRQoL in caregivers of patients with advanced NSCLC. Conclusions The HRQoL of caregivers for patients with advanced NSCLC was investigated for the first time in China. The informal caregivers experience decreased HRQoL, with anxiety /depression problems being reported the most. The findings of this study would provide extensive information on the HRQoL of advanced NSCLC patients' caregivers for future health-promoting self-care.

Abstract Fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) are key indicators reflecting blood glucose control in type 2 diabetes mellitus (T2DM) patients. The purpose of this study is to establish a predictive model for blood glucose changes in T2DM patients after 3 months of treatment, achieving personalized treatment.A retrospective study was conducted on type 2 diabetes mellitus real-world medical data from 4 cities in Sichuan Province, China from January 2015 to December 2020. After data preprocessing, data inputting, data sampling, and feature screening, 16 kinds of machine learning methods were used to construct prediction models, and 5 prediction models with the best prediction performance were screened respectively. A total of 100,000 cases were included to establish the FBG model, and 2,169 cases were established to establish the HbA1c model. The best prediction model both of FBG and HbA1c finally obtained are realized by ensemble learning and modified random forest inputting, the AUC values are 0.819 and 0.970, respectively. The most important indicators of the FBG and HbA1c prediction model were FBG and HbA1c. Medication compliance, follow-up outcome, dietary habits, BMI, and waist circumference also had a greater impact on FBG levels. The prediction accuracy of the models of the two blood glucose control indicators is high and has certain clinical applicability.HbA1c and FBG are mutually important predictors, and there is a close relationship between them.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered a “multisystem” disease that simultaneously suffers from metabolic diseases and hepatic steatosis. Some may develop into liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Given the close connection between metabolic diseases and fatty liver, it is urgent to identify drugs that can control metabolic diseases and fatty liver as a whole and delay disease progression. Ferroptosis, characterized by iron overload and lipid peroxidation resulting from abnormal iron metabolism, is a programmed cell death mechanism. It is an important pathogenic mechanism in metabolic diseases or fatty liver, and may become a key direction for improving MASLD. In this article, we have summarized the physiological and pathological mechanisms of iron metabolism and ferroptosis, as well as the connections established between metabolic diseases and fatty liver through ferroptosis. We have also summarized MASLD therapeutic drugs and potential active substances targeting ferroptosis, in order to provide readers with new insights. At the same time, in future clinical trials involving subjects with MASLD (especially with the intervention of the therapeutic drugs), the detection of serum iron metabolism levels and ferroptosis markers in patients should be increased to further explore the efficacy of potential drugs on ferroptosis.

ABSTRACT: Objectives: Appropriate dosage of vancomycin is critical for safety and efficacy in treating infectious diseases. Various population pharmacokinetic (PPK) models have been established. To lay a foundation for the clinical application, it is important to perform external validation of the published model. The aim of this study was to find the most suitable vancomycin PPK model for treatment of infection in China amongst all studied models developed for adults. Methods: A systematic literature search of published population vancomycin pharmacokinetic analyses was performed using the PubMed database. The identified models were evaluated in ten independent cohorts from China. Nonlinear mixed-effects modeling (NONMEM) was used for data analysis. The median prediction error (MPE), the distribution of prediction error (PE), and normalized prediction distribution errors (NPDE) were calculated and described. Predictive performance was evaluated by bias and accuracy. Results: A total of 449 vancomycin concentrations from 397 infected participants were used for external validation. The MPE of the three models from the Chinese population was less than 10%. Half of the models had an acceptable MPE. For patients with different site infections and different renal functions, each model differed in its predictive ability to some extent. The NPDE results showed that all models had an obvious bias. Conclusions: None of the models had good performance in both prediction- and simulation-based diagnostics. Carrying out sufficient external validation of the PPK model before clinical application is of utmost importance. In clinical practice, the model's population closest to the application population should be used.

ObjectiveThis study was conducted to estimate the direct non-medical cost of advanced non-small cell lung cancer (NSCLC) patients and explore whether its associated factors vary by health status.MethodsData were obtained from 13 centers in five provinces for patients with advanced NSCLC in China. The direct non-medical cost of patients since the patients were diagnosed with NSCLC included the cost of transportation, accommodation, meal, hired caregiving, and nutrition. We measured patients' health status by EQ-5D-5L instrument and divided them into good (≥0.75) and poor (

BackgroundSince 2009, a series of ambitious health system reforms have been launched in China, including the zero mark-up drug policy (ZMDP); the policy was intended to reduce substantial medicine expenses for patients by abolishing the 15% mark-up on drugs. This study aims to evaluate the impacts of ZMDP on medical expenditures from the perspective of disease burden disparities in western China.MethodTwo typical diseases including Type 2 diabetes mellitus (T2DM) in internal medicine and cholecystolithiasis (CS) in surgery were selected from medical records in a large tertiary level-A hospital in SC Province. The monthly average medical expenses of patients from May 2015 to August 2018 were extracted to construct an interrupted time series (ITS) model to evaluate the impact of policy implementation on the economic burden.ResultsA total of 5,764 cases were enrolled in our study. The medicine expenses for T2DM patients maintained a negative trend both before and after the intervention of ZMDP. It had declined by 74.3 CNY (P < 0.001) per month on average in the pre-policy period and subsequently dropped to 704.4 CNY (P = 0.028) immediately after the policy. The level change of hospitalization expenses was insignificant (P = 0.197), with a reduction of 677.7 CNY after the policy, while the post-policy long-term trend was significantly increased by 97.7 CNY (P = 0.035) per month contrasted with the pre-policy period. In addition, the anesthesia expenses of T2DM patients had a significant increase in the level under the impact of the policy. In comparison, the medicine expenses of CS patients significantly decreased by 1,014.2 CNY (P < 0.001) after the policy, while the total hospitalization expenses had no significant change in level and slope under the influence of ZMDP. Furthermore, the expenses of surgery and anesthesia for CS patients significantly increased by 320.9 CNY and 331.4 CNY immediately after the policy intervention.ConclusionOur study indicated that the ZMDP has been an effective intervention to reduce the excessive medicine expenses for both researched medical and surgical diseases, but failed to show any long-term advantage. Moreover, the policy has no significant impact on relieving the overall hospitalization burden for either condition.

Objectives: This study aimed to describe and compare health-related quality of life (HRQoL) among populations with normal glycemic levels, prediabetes, and diabetes in southwest China and to offer baseline data that can be easily compared to other regions in China or across countries.Methods: A quality of life survey based on the EuroQoL-5 Dimension-5 level (EQ-5D-5L) scale was conducted through face-to-face or telephone interviews. A total of 403 respondents with diabetes, 404 with prediabetes, and 398 with normal blood glucose were enrolled in the survey. Propensity score matching (PSM) was used to decrease the bias of three groups, conditioned on age and gender, body mass index (BMI), and household income. For the three groups, we matched two groups first and then matched the result with the third group. Differences among groups were compared by chi-square test one-way ANOVA after adjusting by PSM.Results: In general, the blood glucose of people with diabetes was generally well-controlled in southwest China, but they were often accompanied by the circulatory system and nutritional metabolic diseases. Ninety-nine individuals from each group were matched. The EuroQoL-5 Dimension index of the population with normal glycemic levels, prediabetes, and patients with diabetes was 0.901, 0.948, and 0.897. The EuroQol-visual analog scales (EQ-VAS) scores of each group above were 73.76, 77.45, and 68.34. HRQoL in males was higher than that of females in the three study groups. The results after PSM were consistent with that before matching.Conclusion: There was a general trend that patients were associated with a decline of HRQoL from the prediabetic population, population with normal glycemic levels to diabetic population. Pain/discomfort and anxiety/depression might not be specific for the population with or without diabetes.

Objectives: This study analyzed the long-term cost-effectiveness of fluticasone/umeclidinium/vilanterol triple combination (FF/UMEC/VI) vs. budesonide/formoterol double combination (BUD/FOR) in the treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD) and provides evidence for COPD treatment decisions.Methods: From the perspective of the healthcare system, a Markov model was established that consists of four states—stable period, non-severely deteriorating period, severely deteriorating period, and death—according to real-world COPD progression. The model period comprises 6 months, with a cycle length of 14 years. The initial state, transition probabilities, costs, and utility data were collected from the FULFIL trial, published literature, hospital record surveys, and China Health Statistics Yearbook. The discount rate was 5%, and the threshold was set as the Chinese per capita GDP in 2020 (¥72,447). The cost, utility, transition probabilities, and discount rate were calculated through TreeagePro11 software. The results were analyzed via one-way factor analysis and probability sensitivity analysis.Results: The baseline study shows that the 14-year treatment for FF/UMEC/VI and BUD/FOR groups are ¥199,765.55 and ¥173,030.05 with effectiveness at 8.54 quality-adjusted life years (QALYs) and 7.73 QALYs, respectively. The incremental cost-effectiveness ratio is ¥33,006.80/QALY, which is below the threshold. A tornado diagram of a one-way sensitivity analysis shows that the top three factors that affected the results are the non-severe deterioration rates of FF/UMEC/VI, the cost of FF/UMEC/VI and the non-severe deterioration rates of BUD/FOR. Probabilistic sensitivity analysis shows that FF/UMEC/VI (compared to BUD/FOR) can be made cost-effective under the willingness-to-pay (WTP) threshold (¥38,000). Furthermore, the likelihood of cost-effectiveness increases with a higher WTP.Conclusions: Compared with the double combination (BUD/FOR), the triple combination (FF/UMEC/VI) is more cost-effective under the Chinese per capita GDP threshold.

ObjectiveThe prognosis of patients with breast cancer liver metastasis (BCLM) was poor. We aimed at constructing a nomogram to predict overall survival (OS) for BCLM patients using the SEER (Surveillance Epidemiology and End Results) database, thus choosing an optimized therapeutic regimen to treat.MethodsWe identified 1173 patients with BCLM from the SEER database and randomly divided them into training (n=824) and testing (n=349) cohorts. The Cox proportional hazards model was applied to identify independent prognostic factors for BCLM, based on which a nomogram was constructed to predict 1-, 2-, and 3-year OS. Its discrimination and calibration were evaluated by the Concordance index (C-index) and calibration plots, while the accuracy and benefits were assessed by comparing it to AJCC-TNM staging system using the decision curve analysis (DCA). Kaplan-Meier survival analyses were applied to test the clinical utility of the risk stratification system.ResultsGrade, marital status, surgery, radiation therapy, chemotherapy, CS tumor size, tumor subtypes, bone metastatic, brain metastatic, and lung metastatic were identified to be independent prognostic factors of OS. In comparison with the AJCC-TNM staging system, an improved C-index was obtained (training group: 0.701 vs. 0.557, validation group: 0.634 vs. 0.557). The calibration curves were consistent between nomogram-predicted survival probability and actual survival probability. Additionally, the DCA curves yielded larger net benefits than the AJCC-TNM staging system. Finally, the risk stratification system can significantly distinguish the ones with different survival risk based on the different molecular subtypes.ConclusionWe have successfully built an effective nomogram and risk stratification system to predict OS in BCLM patients, which can assist clinicians in choosing the appropriate treatment strategies for individual BCLM patients.

Purpose: The objective of this study was to evaluate the efficacy of machine learning algorithms in predicting risks of complications and poor glycemic control in nonadherent type 2 diabetes (T2D).Materials and Methods: This study was a real-world study of the complications and blood glucose prognosis of nonadherent T2D patients. Data of inpatients in Sichuan Provincial People’s Hospital from January 2010 to December 2015 were collected. The T2D patients who had neither been monitored for glycosylated hemoglobin A nor had changed their hyperglycemia treatment regimens within the last 12 months were the object of this study. Seven types of machine learning algorithms were used to develop 18 prediction models. The predictive performance was mainly assessed using the area under the curve of the testing set.Results: Of 800 T2D patients, 165 (20.6%) met the inclusion criteria, of which 129 (78.2%) had poor glycemic control (defined as glycosylated hemoglobin A ≥7%). The highest area under the curves of the testing set for diabetic nephropathy, diabetic peripheral neuropathy, diabetic angiopathy, diabetic eye disease, and glycosylated hemoglobin A were 0.902 ± 0.040, 0.859 ± 0.050, 0.889 ± 0.059, 0.832 ± 0.086, and 0.825 ± 0.092, respectively.Conclusion: Both univariate analysis and machine learning methods reached the same conclusion. The duration of T2D and the duration of unadjusted hypoglycemic treatment were the key risk factors of diabetic complications, and the number of hypoglycemic drugs was the key risk factor of glycemic control of nonadherent T2D. This was the first study to use machine learning algorithms to explore the potential adverse outcomes of nonadherent T2D. The performances of the final prediction models we developed were acceptable; our prediction performances outperformed most other previous studies in most evaluation measures. Those models have potential clinical applicability in improving T2D care.