The effects of nirmatrelvir/ritonavir on tacrolimus levels in lung transplant recipients: A single-center study.

BACKGROUND: Lung transplant recipients (LTRs) have a higher risk of hospitalization and mortality due to COVID-19 compared with the immunocompetent population. The use of nirmatrelvir/ritonavir (NR), an effective oral treatment for COVID-19, is quite challenging due to its potent drug-drug interactions with immunosuppressants and azole antifungals. As there are few clinical reports of the use of NR in LTRs, we measured tacrolimus levels in patients receiving NR in our hospital to improve safety when prescribing NR. METHODS: In total, 48 adult LTRs who received NR between November 19, 2022, and January 19, 2023, at China-Japan Friendship Hospital were retrospectively included and followed for 20 days after initiating NR. Tacrolimus was held at least 12 h before initiating NR and re-administered based on the trough levels after completing NR treatment. All concomitant medications, drug concentrations, laboratory results, and genotypes were recorded and analyzed. RESULTS: Most patients showed stable tacrolimus trough levels despite high individual variability. Four patients exhibited supratherapeutic trough levels of tacrolimus (more than 15 ng/mL). Two patients who received 0.5 mg of tacrolimus during NR treatment had trough levels below 3.0 ng/mL. In addition, we found that in 13 patients, the trough levels were 130% of baseline after cessation of tacrolimus, and logistic regression revealed that increased trough level was significantly associated with age more than 60 years. CONCLUSIONS: NR can be safely used in LTRs with close monitoring of tacrolimus levels and appropriate dose adjustments. However, more attention should be paid to elderly patients, as NR may more severely affect their drug metabolism. Due to the limited sample size, further studies are needed to guide the optimal use of tacrolimus following treatment with NR and explore the risk factors significantly affecting the interactions between NR and tacrolimus.

Computational Insights into SARS-CoV-2 Main Protease Mutations and Nirmatrelvir Efficacy: The Effects of P132H and P132H-A173V.

Nirmatrelvir, a pivotal component of the oral antiviral Paxlovid for COVID-19, targets the SARS-CoV-2 main protease (Mpro) as a covalent inhibitor. Here, we employed combined computational methods to explore how the prevalent Omicron variant mutation P132H, alone and in combination with A173V (P132H-A173V), affects nirmatrelvir's efficacy. Our findings suggest that P132H enhances the noncovalent binding affinity of Mpro for nirmatrelvir, whereas P132H-A173V diminishes it. Although both mutants catalyze the rate-limiting step more efficiently than the wild-type (WT) Mpro, P132H slows the overall rate of covalent bond formation, whereas P132H-A173V accelerates it. Comprehensive analysis of noncovalent and covalent contributions to the overall binding free energy of the covalent complex suggests that P132H likely enhances Mpro sensitivity to nirmatrelvir, while P132H-A173V may confer resistance. Per-residue decompositions of the binding and activation free energies pinpoint key residues that significantly affect the binding affinity and reaction rates, revealing how the mutations modulate these effects. The mutation-induced conformational perturbations alter drug-protein local contact intensities and the electrostatic preorganization of the protein, affecting noncovalent binding affinity and the stability of key reaction states, respectively. Our findings inform the mechanisms of nirmatrelvir resistance and sensitivity, facilitating improved drug design and the detection of resistant strains.

Exploratory associations of tacrolimus exposure and clinical outcomes after lung transplantation: A retrospective, single center experience.

PURPOSE: This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation. METHODS: This retrospective observational study enrolled a total of 228 lung transplant recipients. TAC trough levels (C0) were collected for 3 intervals: 0-3 months, 3-12 months, and 12-24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed. Patients were further divided into groups based on the C0 cut-off value of 8 ng/mL and IPV cut-off value of 30%. Cox proportional hazards regression models were used to explore the potential impact of C0 and IPV on outcomes of interests, including de-novo donor-specific antibodies (dnDSA), chronic lung allograft dysfunction (CLAD) and mortality. RESULTS: The influence of CYP3A5*3 polymorphism was only significant for C0 and IPV during the first 3 months. Low C0 (< 8 ng/mL) at 3-12 months increased the risk of dnDSA (hazard ratio [HR] 2.696, 95% confidence interval [CI] 1.046-6.953) and mortality (HR 2.531, 95% CI 1.368-4.685), while High IPV (≥ 30%) during this period was associated with an increased risk of mortality (HR 2.543, 95% CI 1.336-4.839). Patients with Low C0/High IPV combination had significantly higher risks for dnDSA (HR 4.381, 95% CI 1.279-15.008) and survival (HR 6.179, 95% CI 2.598-14.698), surpassing the predictive power provided by C0 or IPV alone. CONCLUSION: A combination of Low C0/High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation.

Predictors and influence of postoperative moderate-to-severe pain of PACU in the patients with malignancy.

BACKGROUND: This study was identified the risk factors for and designed to investigate influence of postoperative moderate-to-severe pain of post anaesthesia care unit (PACU) in patients with malignancy. METHODS: A retrospective study was performed on 22,600 cancer patients with malignancy who underwent elective radical surgery in the new hospital of First Affiliated Hospital of Wenzhou Medical University, between January 2016 and June 2021. All patients were transferred to the PACU after tracheal extubation. Patients were divided into two groups according to a visual analogue scale (VAS) score of > 3: the no-moderate-severe-pain group and moderate-to-severe-pain group. Data pertaining to demographic, surgical, anaesthetic, and other factors were recorded. Lasso and logistic regression analysis was performed to explore the risk factors, then a nomogram was constructed to predict the moderate-severe-pain in the PACU. Validation was performed by using another 662 cancer patients in old hospital. The ROC curves and calibration curve were used to evaluate the accuracy and predictive ability of the nomogram. RESULTS: The incidence of postoperative moderate-to-severe pain of PACU in patients with malignancy was 1.42%. Gender, type of surgery, postoperative use of PCA, intraoperative adjuvant opioid agonists, NSAIDS, epidural analgesia, duration of anaesthesia, intraoperative massive haemorrhage, PACU vomiting were independent predictors for postoperative moderate-to-severe pain of PACU in the patients with malignancy. The area under the ROC curve of the predictive models in the primary and validation groups were 0.817 and 0.786, respectively. Moderate-to-severe pain in the PACU correlated with hypertension, hyperglycaemia, agitation, and hypoxemia (P < 0.05). CONCLUSIONS: The prediction model for postoperative moderate-to-severe pain of PACU in patients with malignancy has good predictive ability and high accuracy, which is helpful for PACU medical staff to identify and prevent postoperative moderate-to-severe pain in advance. TRIAL REGISTRATION: The study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (No.KY2021-097) and registered in the Chictr.org.cn registration system on 06/12/2021 (ChiCTR2100054013).

CB1 Receptor Negative Allosteric Modulators as a Potential Tool to Reverse Cannabinoid Toxicity.

While the opioid crisis has justifiably occupied news headlines, emergency rooms are seeing many thousands of visits for another cause: cannabinoid toxicity. This is partly due to the spread of cheap and extremely potent synthetic cannabinoids that can cause serious neurological and cardiovascular complications-and deaths-every year. While an opioid overdose can be reversed by naloxone, there is no analogous treatment for cannabis toxicity. Without an antidote, doctors rely on sedatives, with their own risks, or 'waiting it out' to treat these patients. We have shown that the canonical synthetic 'designer' cannabinoids are highly potent CB1 receptor agonists and, as a result, competitive antagonists may struggle to rapidly reverse an overdose due to synthetic cannabinoids. Negative allosteric modulators (NAMs) have the potential to attenuate the effects of synthetic cannabinoids without having to directly compete for binding. We tested a group of CB1 NAMs for their ability to reverse the effects of the canonical synthetic designer cannabinoid JWH018 in vitro in a neuronal model of endogenous cannabinoid signaling and also in vivo. We tested ABD1085, RTICBM189, and PSNCBAM1 in autaptic hippocampal neurons that endogenously express a retrograde CB1-dependent circuit that inhibits neurotransmission. We found that all of these compounds blocked/reversed JWH018, though some proved more potent than others. We then tested whether these compounds could block the effects of JWH018 in vivo, using a test of nociception in mice. We found that only two of these compounds-RTICBM189 and PSNCBAM1-blocked JWH018 when applied in advance. The in vitro potency of a compound did not predict its in vivo potency. PSNCBAM1 proved to be the more potent of the compounds and also reversed the effects of JWH018 when applied afterward, a condition that more closely mimics an overdose situation. Lastly, we found that PSNCBAM1 did not elicit withdrawal after chronic JWH018 treatment. In summary, CB1 NAMs can, in principle, reverse the effects of the canonical synthetic designer cannabinoid JWH018 both in vitro and in vivo, without inducing withdrawal. These findings suggest a novel pharmacological approach to at last provide a tool to counter cannabinoid toxicity.

[Generational differences in overweight and obesity among Chinese adult resident].

OBJECTIVE: To analyze the generational differences in overweight/obesity prevalence and central obesity prevalence among Chinese adult residents aged 20 years and above at the same ages. METHODS: A total of 38 908 healthy adult residents aged 20 years and above from "the China Health and Nutrition Survey" in 1991, 2000, 2009, and 2018 were selected for this study. Based on age at the time of the survey, the study subjects were divided into 6 age groups(20-29, 30-39, 40-49, 50-59, 60-69, and ≥70 years old) corresponding to 9 different generations of births in 10, 20, 30, 40, 50, 60, 70, 80, and 90 generations, respectively. All analyses were stratified by sex. A chi-square test was used to compare generational differences in overweight/obesity and central obesity at similar ages in populations born in different generations. Non-parametric tests were used to compare generational differences in BMI and waist circumference. RESULTS: (1) Body mass index(BMI), overweight/obesity rate, waist circumference, and central obesity rate showed unfavorable generational differences(P<0.0001) among different generations of residents at similar ages. BMI, overweight/obesity prevalence, waist circumference, and central obesity prevalence were higher in the younger generation. Overweight/obesity and central obesity occurred at an earlier age in the younger generation. (2) Generational differences in overweight/obesity rates and central obesity rates followed gender specificity. Unfavorable generational differences(P<0.0001) occurred in overweight/obesity as well as central obesity between the two oldest generations of females, with maximum differences of 15.5% and 8.0%. Unfavorable generational differences(P<0.0001) occurred in overweight/obesity between the two adjacent generations of men and in central obesity between the two youngest generations of men, with maximum differences of 19.5% and 17.0%. CONCLUSION: The prevalence of overweight/obesity and central obesity among Chinese adults showed unfavorable generational differences. The prevalence of overweight/obesity and central obesity was higher in the younger generation. The younger generation develops overweight/obesity at an earlier age.

[Trends of eating out among males in China and its correlation with nutrition and health during 2000 to 2018].

OBJECTIVE: To analyze the trend of eating out among Chinese male adults and explore the association between eating out and dietary nutrition and health. METHODS: Males aged 18 and above with complete data were selected from China Health and Nutrition Survey 2000, 2004, 2006, 2009, 2011, 2015 and 2018. Eating out behavior was defined as having consumption of food prepared outside the home during the three consecutive 24-h dietary recalls period. Cochran-Armitage trend test was used to analyze the trend of prevalence of eating out and the energy contribution from eating out foods in males from 2000 to 2018. Analysis of covariance was used to compare the differences in several food and dietary nutrient intakes and nutritional indicators by eating out in 2018. RESULTS: The prevalence of eating out among Chinese male adults increased from 48.49% in 2000 to 57.51% in 2018, showing an increased trend followed by a decreased trend. Males in the 18-29 years old group, urban group, high income group, and high education level group had a higher rate of eating out(P<0.05). The energy contribution from eating out foods increased from 21.80% in 2000 to 28.77% in 2018, showing a slow upward trend. In 2018, the intake of rice, tubers and vegetables was lower in the eating out group, while intake of wheat, fruits, livestock and poultry meat, aquatic products, eggs and milk in eating out group was higher than those in the non-eating out group(P<0.05). The eating out group had a higher intake of energy, fat, protein, cholesterol, calcium, zinc, vitamin B_1 and vitamin B_2 than the non-eating out group(P<0.05). The eating out group had lower levels of systolic blood pressure, HDL-C, blood glucose and glycosylated hemoglobin than the counterparts. The levels of BMI, waist, body fat percentage, diastolic blood pressure and TG were higher in the eating out group than in the non-eating out group. CONCLUSION: From 2000 to 2011, the eating out rate of males in China showed an upward trend, and a downward trend after 2011. At the same time, the energy contribution of eating out foods is increasing. Eating out was associated with major food and nutrients intake and indicators of nutritional status in male adults.

Impact of statin treatment and exposure on the risk of chronic allograft dysfunction in Chinese lung transplant recipients.

PURPOSE: Chronic lung allograft dysfunction (CLAD) was a common complication following lung transplantation that contributed to long-term morbidity and mortality. Statin therapy had been suggested to attenuate recipient inflammation and immune response, potentially reducing the risk and severity of CLAD. This study aimed to evaluate the impact of statin use and in vivo exposure on the incidence of CLAD in lung transplant recipients (LTRs), as well as their effects on immune cells and inflammatory factors. METHODS: A retrospective cohort study was conducted on patients who underwent lung transplantation between January 2017 and December 2020. The incidence of CLAD, as per the 2019 ISHLT criteria, was assessed as the clinical outcome. The plasma concentrations of statin were measured using a validated UPLC-MS/MS method, while inflammation marker levels were determined using ELISA kits. RESULTS: The statin group exhibited a significantly lower rate of CLAD (P = 0.002). Patients receiving statin therapy showed lower CD4+ T-cell counts, total T-lymphocyte counts, and IL-6 levels (P = 0.017, P = 0.048, and P = 0.038, respectively). Among the CLAD groups, the atorvastatin level (2.51 ± 1.31 ng/ml) was significantly lower than that in the non-CLAD group (OR = 1.438, 95%CI (1.007-2.053), P = 0.046). CONCLUSION: Statin therapy significantly reduced the incidence of CLAD, as well as immune cell counts and inflammatory cytokine levels in LTRs. Although the statin exposure was significantly lower in CLAD patients, it was not associated with the incidence of CLAD.

Tensorial Fourier expansion of orientation distribution function defined on the orthogonal group O(3).

Recently, Man and Du, in the context of classical texture analysis where the orientation distribution function (ODF) is defined on the rotation group SO(3), presented a systematic procedure by which the classical expansion of an ODF truncated at the order [Formula: see text] can be directly rewritten as a tensorial Fourier expansion truncated at the same order. In classical texture analysis, the groups of crystallite and texture symmetries are assumed to be subgroups of SO(3), which is unreasonable, say, for aggregates of crystallites in a crystal class defined by an improper point group. In this paper, we consider ODFs defined on the orthogonal group O(3) and extend the aforementioned procedure to write down tensorial Fourier expansions for polycrystals with crystallite symmetry defined by any of the 21 improper point groups. Examples that illustrate the general procedure are given. This article is part of the theme issue 'Foundational issues, analysis and geometry in continuum mechanics'.

Impact of Transcutaneous Electrical Acupoint Stimulation on Delayed Neurocognitive Recovery in Elderly Patients Following Bronchoscopy.

Background: Postoperative cognitive dysfunction (POCD) is a significant neurological issue after surgery, linked to increased mortality, extended hospital stays, higher costs, and workforce dropout. However, effective prevention methods for POCD remain elusive. Objective: This study aims to investigate the impact of transcutaneous electrical acupoint stimulation (TEAS) on the cognitive function of elderly patients after bronchoscopy. Design: The research team conducted a double-blind, randomized, controlled clinical trial. Setting: The study was conducted at a university hospital in Wenzhou, China. Participants: The study involved 80 patients who underwent bronchoscopy between December 2019 and September 2020. Intervention: The participants were randomly assigned to two groups, each with 40 participants: the intervention and control groups. The intervention group received Transcutaneous Electrical Acupoint Stimulation (TEAS) for 30 minutes before anesthesia, while the control group had electrodes applied but did not receive stimulation. Outcome Measures: Seven neuropsychological tests were administered before the operation and one day afterwards. Participants were also assessed via telephone after 7 days and one-month post-operation. Results: The TEAS group exhibited a significant reduction in the incidence of delayed neurocognitive recovery (DNR) compared to the control group on the 7th-day post-operation, although no such difference was observed at 1 day and 30 days post-operation. Conclusion: TEAS demonstrated positive effects in preventing cognitive decline in elderly patients undergoing bronchoscopy.

Identification of and Mechanistic Insights into SARS-CoV-2 Main Protease Non-Covalent Inhibitors: An In-Silico Study.

The indispensable role of the SARS-CoV-2 main protease (Mpro) in the viral replication cycle and its dissimilarity to human proteases make Mpro a promising drug target. In order to identify the non-covalent Mpro inhibitors, we performed a comprehensive study using a combined computational strategy. We first screened the ZINC purchasable compound database using the pharmacophore model generated from the reference crystal structure of Mpro complexed with the inhibitor ML188. The hit compounds were then filtered by molecular docking and predicted parameters of drug-likeness and pharmacokinetics. The final molecular dynamics (MD) simulations identified three effective candidate inhibitors (ECIs) capable of maintaining binding within the substrate-binding cavity of Mpro. We further performed comparative analyses of the reference and effective complexes in terms of dynamics, thermodynamics, binding free energy (BFE), and interaction energies and modes. The results reveal that, when compared to the inter-molecular electrostatic forces/interactions, the inter-molecular van der Waals (vdW) forces/interactions are far more important in maintaining the association and determining the high affinity. Given the un-favorable effects of the inter-molecular electrostatic interactions-association destabilization by the competitive hydrogen bond (HB) interactions and the reduced binding affinity arising from the un-compensable increase in the electrostatic desolvation penalty-we suggest that enhancing the inter-molecular vdW interactions while avoiding introducing the deeply buried HBs may be a promising strategy in future inhibitor optimization.

[Trajectories of body mass index and risk of hypertension and blood pressure among Chinese adults].

OBJECTIVE: To explore the relationship between trajectories of body mass index(BMI) and the risk of hypertension and blood pressure among Chinese adults. METHODS: The current study was based on data from 10 waves of the China Health and Nutrition Survey from 1991 to 2018. A multistage stratified random sample was used in this study.11885 adults whose BMI had been measured at least three times were included in the study. Group-based trajectory modeling(GBTM) was used to identify the BMI trajectories in different genders, Cox regression model was used to analyze the association between BMI trajectories and the risk of incident hypertension. Generalized linear model was used to analyze the association between BMI trajectories and the blood pressure level. RESULTS: Three distinct BMI trajectories were determined for both genders: normal-stable group, normal-overweight group, obesity-stable group. The numbers of each group among males were 3595(63.23%), 1412(24.83%) and 679(11.94%), and the numbers of each group among females were 4566(73.66%), 1214(19.58%) and 419(6.76%). Taking the normal-stable group as a reference, after adjusting for confounding factors, the normal-overweight group, obesity-stable group had 1.14(1.03-1.25), P=0.01 and 1.42(1.24-1.63), P<0.01 increased risk(HR(95% CI)) of developing hypertension in male. The normal-overweight group, obesity-stable group had 1.29(1.13-1.46), P<0.01 and 1.58(1.23-2.03), P<0.01 increased risk of developing hypertension in female. Taking the normal-stable group as a reference, after adjusting for confounding factors, the systolic blood pressure[ß(95% CI)] in the male normal-overweight group and obesity-stable group increased by 3.01(1.88-4.14)mmHg, P<0.01 and 5.44(3.85-7.03)mmHg, P<0.01 respectively. The diastolic blood-pressure level was increased by 2.20(1.48-2.91)mmHg, P<0.01 and 4.04(3.04-5.04)mmHg, P<0.01 respectively. The systolic blood pressure in the female normal-overweight group and obesity-stable group were increased by 3.65(2.44-4.85)mmHg, P<0.01 and 2.96(0.97-4.94)mmHg, P<0.01 respectively. The diastolic blood pressure level was increased by 3.11(2.38-3.86)mmHg, P<0.01 and 1.25(0.03-2.47)mmHg, P=0.05 respectively. CONCLUSION: Both the trajectory of BMI increasing with age and the trajectory of maintaining a high BMI level increased the risk of hypertension, and blood pressure also increased significantly compared with those who maintained normal BMI.

[Evaluation of the front-of-package warning labels of prepackaged food in China based on focus group discussion].

OBJECTIVE: To understand the public's perceptions and preferences on the designed front-of-package warning labels of prepackaged food, and to evaluate and identify the effective warning label. METHODS: A total of 116 participants were recruited from six provinces(autonomous regions/municipalities) in China. Focus group discussions were conducted with four types of warning labels on prepackaged food. And the score of attitude on different warning labels were compared. RESULTS: There was no difference in the total score of the four warning labels. Total score of black shield label was higher in citizen participants and college education level participants than in their respective counterparts(P<0.05). Parents or primary caregiver of children under 16 years old gave higher scores to each labels than their respective counterparts(P<0.05). The black shield label was most likely to attract the attention of the respondents, most likely to influence the decision on eating and drinking, and most likely to have an unhealthy warning effect. The yellow hexagonal label was least likely to attract the attention of the respondents, least likely to affect the decision to eat and drink food, and least likely to have an unhealthy warning effect. CONCLUSION: Black shield warning label is the most effective.

Influence of endotracheal tube and laryngeal mask airway for general anesthesia on perioperative adverse events in patients undergoing laparoscopic hysterectomy: A propensity score-matched analysis.

Background: To compare perioperative adverse events between general anesthesia with endotracheal tube (ETT) and general anesthesia with laryngeal mask airway (LMA) in patients undergoing laparoscopic hysterectomy. Materials and Methods: This was a large sample retrospective, propensity score-matched (PSM) study. We collected the data of 6739 female patients who underwent laparoscopic hysterectomy between January 2016 and June 2021 in our hospital, China. Patients were divided into two groups (ETT group and LMA group) according to different airway management modes. Data on all perioperative adverse events were collected. PSM analysis was performed to control confounding factors and differences in baseline values between the two groups. Finally, 4150 female patients were recruited after PSM. Results: The total number of patients taking intraoperative vasoactive drugs during surgery was higher in the ETT group than in the LMA group (P = 0.04). The LMA group had a higher incidence of vomiting (51 [2.46%]) and somnolence (165 [7.95]) in the postanesthesia care unit (PACU) than the ETT group (71 [3.42%] and 102 [4.92%], respectively) (P = 0.02 and P < 0.001). Hypothermia was significantly higher in the LMA group (183 [10.36%]) than in the ETT group (173 [8.34%]) in the PACU (P = 0.03). The number of patients with sore throat was significantly higher in the ETT group (434 [20.02%]) than in the LMA group (299 [14.41%]) in the ward (P < 0.001). Other variables such as hypoxemia, moderate to severe pain, abdominal distension, diarrhea, sleep disorders, wound bleeding, and skin itch were not significantly different between the two groups (P > 0.05). Conclusion: The ETT group had more incidences of vomiting, sore throat, and cough complications and needed more drug treatment than the LMA group. LMA is a better airway management mode and LMA general anesthesia can be safely used in patients undergoing laparoscopic nonemergency hysterectomy.

Association of gut microbiota with glycaemic traits and incident type 2 diabetes, and modulation by habitual diet: a population-based longitudinal cohort study in Chinese adults.

AIMS/HYPOTHESIS: The gut microbiome is mainly shaped by diet, and varies across geographical regions. Little is known about the longitudinal association of gut microbiota with glycaemic control. We aimed to identify gut microbiota prospectively associated with glycaemic traits and type 2 diabetes in a geographically diverse population, and examined the cross-sectional association of dietary or lifestyle factors with the identified gut microbiota. METHODS: The China Health and Nutrition Survey is a population-based longitudinal cohort covering 15 provinces/megacities across China. Of the participants in that study, 2772 diabetes-free participants with a gut microbiota profile based on 16S rRNA analysis were included in the present study (age 50.8 ± 12.7 years, mean ± SD). Using a multivariable-adjusted linear mixed-effects model, we examined the prospective association of gut microbiota with glycaemic traits (fasting glucose, fasting insulin, HbA1c and HOMA-IR). We constructed a healthy microbiome index (HMI), and used Poisson regression to examine the relationship between the HMI and incident type 2 diabetes. We evaluated the association of dietary or lifestyle factors with the glycaemic trait-related gut microbiota using a multivariable-adjusted linear regression model. RESULTS: After follow-up for 3 years, 123 incident type 2 diabetes cases were identified. We identified 25 gut microbial genera positively or inversely associated with glycaemic traits. The newly created HMI (per SD unit) was inversely associated with incident type 2 diabetes (risk ratio 0.69, 95% CI 0.58, 0.84). Furthermore, we found that several microbial genera that were favourable for the glycaemic trait were consistently associated with healthy dietary habits (higher consumption of vegetable, fruit, fish and nuts). CONCLUSIONS/INTERPRETATION: Our results revealed multiple gut microbiota prospectively associated with glycaemic traits and type 2 diabetes in a geographically diverse population, and highlighted the potential of gut microbiota-based diagnosis or therapy for type 2 diabetes. DATA AVAILABILITY: The code for data analysis associated with the current study is available at https://github.com/wenutrition/Microbiota-T2D-CHNS.

Gut microbiota signatures of long-term and short-term plant-based dietary pattern and cardiometabolic health: a prospective cohort study.

BACKGROUND: The interplay among the plant-based dietary pattern, gut microbiota, and cardiometabolic health is still unclear, and evidence from large prospective cohorts is rare. We aimed to examine the association of long-term and short-term plant-based dietary patterns with gut microbiota and to assess the prospective association of the identified microbial features with cardiometabolic biomarkers. METHODS: Using a population-based prospective cohort study: the China Health and Nutrition Survey, we included 3096 participants from 15 provinces/megacities across China. We created an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI). The average PDIs were calculated using repeat food frequency questionnaires collected in 2011 and 2015 to represent a long-term dietary pattern. Short-term dietary pattern was estimated using 3-day 24-h dietary recalls collected in 2015. Fecal samples were collected in 2015 and measured using 16S rRNA sequencing. We investigated the association of long-term and short-term plant-based dietary patterns with gut microbial diversity, taxonomies, and functional pathways using linear mixed models. Furthermore, we assessed the prospective associations between the identified gut microbiome signatures and cardiometabolic biomarkers (measured in 2018) using linear regression. RESULTS: We found a significant association of short-term hPDI with microbial alpha-diversity. Both long-term and short-term plant-based diet indices were correlated with microbial overall structure, whereas long-term estimates explained more variance. Long-term and short-term PDIs were differently associated with microbial taxonomic composition, yet only microbes related to long-term estimates showed association with future cardiometabolic biomarkers. Higher long-term PDI was associated with the lower relative abundance of Peptostreptococcus, while this microbe was positively correlated with the high-sensitivity C-reactive protein and inversely associated with high-density lipoprotein cholesterol. CONCLUSIONS: We found shared and distinct gut microbial signatures of long-term and short-term plant-based dietary patterns. The identified microbial genera may provide insights into the protective role of long-term plant-based dietary pattern for cardiometabolic health, and replication in large independent cohorts is needed.

Modifiable factors of 20-year blood pressure trajectories among normotensives and their associations with hypertension : a prospective study.

Little is known about the impact of modifiable risk factors on blood pressure (BP) trajectories and their associations with hypertension (HTN). We aimed to identify BP trajectories in normotensive Chinese adults and explore their influencing factors and associations with HTN. We used data from 3436 adults with at least four BP measurements between 1989 and 2018 in the China Health and Nutrition Survey, an ongoing cohort study. We measured BP using mercury sphygmomanometers with appropriate cuff sizes in all surveys. We used group-based trajectory modelling to identify BP trajectories between 1989 and 2009 and multiple logistic and Cox regression models to analyse their influencing factors and associations with HTN in 2011-2018. We identified five systolic blood pressure (SBP) trajectories, 'Low-increasing (LI)', 'Low-stable (LS)', 'Moderate-increasing (MI)', 'High-stable (HS)' and 'Moderate-decreasing (MD)', and four diastolic blood pressure (DBP) trajectories classified as 'Low-increasing (LI)', 'Moderate-stable (MS)', 'Low-stable (LS)' and 'High-increasing (HI)'. People with higher physical activity (PA) levels and lower waist circumferences (WC) were less likely to be in the SBP LI, MI, HS and MD groups (P < 0·05). People with higher fruit and vegetable intakes, lower WCs and salt intakes and higher PA levels were less likely to be in the DBP LI, MS and HI groups (P < 0·05). Participants in the SBP HS group (hazard ratio (HR) 2·01) or the DBP LI, MS and HI groups (HR 1·38, 1·40, 1·71, respectively) had higher risks of HTN (P < 0·05). This study suggests that BP monitoring is necessary to prevent HTN in the Chinese population.

Effects of decreasing the out-of-pocket expenses for outpatient care on health-seeking behaviors, health outcomes and medical expenses of people with diabetes: evidence from China.

BACKGROUND: To improve access to outpatient services and provide financial support in outpatient expenses for the insured, China has been establishing its scheme of decreasing the out-of-pocket expenses for outpatient care in recent years. There are 156 million diabetes patients in China which almost accounts for a quarter of diabetes population worldwide. Outpatient services plays an important role in diabetes treatment. The study aims to clarify the effects of decreasing the out-of-pocket expenses for outpatient care on health-seeking behaviors, health outcomes and medical expenses of people with diabetes. METHODS: This study constructed a two-way fixed effect model, utilized 5,996 diabetes patients' medical visits records from 2019 to 2021, to ascertain the influence of decreasing the out-of-pocket expenses for outpatient care on diabetes patients. The dependent variables were diabetes patients' health-seeking behaviors, health outcomes, medical expenses and expenditure of the basic medical insurance funds for them; the core explanatory variable was the out-of-pocket expenses for outpatient care expressed by the annual outpatient reimbursement ratio. RESULTS: With each increase of 1% in the annual outpatient reimbursement ratio: (1) for health-seeking behaviors, a diabetes patient's annual number of outpatient visits and annual number of medical visits increased by 0.021 and 0.014, while the annual number of hospitalizations decreased by 0.006; (2) for health outcomes, a diabetes patient's annual length of hospital stays and average length of a hospital stay decreased by 1.2% and 1.1% respectively, and the number of diabetes complications and Diabetes Complications Severity Index (DCSI) score both decreased by 0.001; (3) for medical expenses, a diabetes patient's annual outpatient expenses, annual inpatient expenses, annual medical expenses and annual out-of-pocket expenses decreased by 2.2%, 4.6%, 2.6% and 4.0%; (4) for expenditure of the basic medical insurance funds for a diabetes patient, the annual expenditure on outpatient services increased by 1.1%, and on inpatient services decreased by 4.4%, but on healthcare services didn't change. CONCLUSION: Decreasing the out-of-pocket expenses for outpatient care appropriately among people with diabetes could make patients have a more rational health-seeking behaviors, a better health status and a more reasonable medical expenses while the expenditure of the basic medical insurance funds is stable totally.

Trajectories of energy intake distribution and subsequent risk of hyperglycemia among Chinese adults: findings from the China Health and Nutrition Survey (1997-2018).

AIMS: Few studies have examined the secular trend of the energy intake distribution, and its effect on future risk of hyperglycemia. This study aims to describe trajectories of energy intake distribution over 12 years and relate them to subsequent risk of hyperglycemia over 9 years of follow-up. METHODS: Our study used ten waves of data from the CHNS survey, a population-based longitudinal survey in China, ongoing since 1989. We examined a cohort of adult participants who were free from diabetes but had at least three waves of dietary data from 1997 to 2009. We assessed energy intake using three consecutive 24 h recalls. We used these data to identify trajectory groups of energy intake distribution by multi-trajectory model based on energy intake proportions of breakfast, lunch, and dinner. We followed up participants for hyperglycemia, diabetes, and impaired fasting glucose for 9 years from 2009 to 2018. Outcomes were ascertained with fasting glucose, serum HbA1c, and self-report of diabetes and/or glucose-lowering medication. We estimated relative risk (RR) for hyperglycemia, diabetes, and impaired fasting glucose by identified trajectory groups using multilevel mixed-effects modified Poisson regression with robust (sandwich) estimation of variance. Gender difference was additionally examined. RESULTS: A total of 4417 participants were included. Four trajectory groups were identified, characterized and labeled by "Energy evenly distributed with steady trend group" (Group 1), "Dinner and lunch energy dominant with relatively steady trend group" (Group 2), "Dinner energy dominant with increasing trend and breakfast energy with declining trend group" (Group 3), and "breakfast and dinner energy dominant with increasing trend group" (Group 4). During 48,091 person-years, 1053 cases of incident hyperglycemia occurred, 537 cases of incident diabetes occurred, and 516 cases of impaired fasting glucose occurred. Compared with Group 1, Group 3 was associated with higher subsequent risk of incident hyperglycemia in 9 years of follow-up (RR = 1.28, 95% CI = 1.02, 1.61). No association was found for incident diabetes and impaired fasting glucose. Among males, Group 3 was associated with higher risk of incident hyperglycemia in 9 years of follow-up (RR = 1.44, 95% CI = 1.07, 1.94). No relationship was found in females. CONCLUSIONS: Energy intake distribution characterized by over 40% of energy intake from dinner with a rising trend over years was associated with higher long-term risk of hyperglycemia in Chinese adults.

Analysis of preoperative sleep quality and related influencing factors in cancer patients.

PURPOSE: The sleep disturbance in cancer patients is more prevalent, and it significantly affects these patients' recovery after the operation. However, the clinical characteristics regarding sleep quality are scarce. This study aimed to evaluate the quality of preoperative sleep quality and its risk factors in different cancer patients requiring elective surgery. PATIENTS AND METHODS: Cancer patients who were scheduled for elective surgery were selected. The demographic data, basic preoperative diseases, and factors related to the preoperative hospital environment were also recorded. Self-made questionnaires (such as gender, age, and personal history), and the Anxiety Self-Assessment Scale were used to assess the patient's underlying condition. The modified Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the preoperative sleep status. RESULTS: A total of 297 patients completed the investigation. The incidence of preoperative sleep disturbance in cancer patients was 47.8%. Multiple logistic regression showed that patients with PSQI ≥ 7 were associated with females (odds ratios [95% confidence intervals]): 1.815 [1.031-3.193], p = 0.039), and the ward space was confined (3.127 [1.016-9.625], p = 0.047), which increased the possibility of sleep disturbance in cancer patients. Meanwhile, increased anxiety levels (1.323 [1.261-1.439], p < 0.001) significantly increased the likelihood of sleep disorders in cancer patients. CONCLUSION: 47.8% of sleep disturbance in cancer patients before surgery. Female patients, preoperative anxiety, and confined ward environment were independent risk factors of subjective sleep disturbance.