Whole-course quality of tuberculosis (TB) care in rural China: a retrospective study based on chart abstraction.

OBJECTIVES: The aim of this study was to assess the quality of tuberculosis (TB) care for the whole course and assess factors that affect completing treatment. DESIGN: This is an observational retrospective study using chart abstraction for the whole course of TB care conducted at two underserved provinces in China. SETTING: The study was conducted from June 2021 to July 2021. All medical records (outpatient and inpatient) for the whole course (6-8 months) of patients with TB newly registered from July 2020 to December 2020 were reviewed and abstracted using predetermined checklists. PARTICIPANTS: A total of 268 outpatient medical records and 126 inpatient records were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome included diagnostic quality, treatment quality and management quality. The secondary outcome was completing treatment. RESULTS: For diagnostic quality, 94.2% of the diagnosis were based on adequate evidence. For treatment quality, 240 (91.6%) outpatients and 100 (85.5%) inpatients took the standard chemotherapy regimens. 234 (87.3%) patients completed treatment. 85.1% of the inpatients prescribed with second-line drugs were inappropriate. For management quality, 128 (47.9%) patients received midterm assessments, but only 47 (19.7%) received sufficient services for the whole course. Patients with TB symptoms were 1.8 times more likely to complete treatment (p=0.011). CONCLUSION: Patients with TB received high-quality diagnosis and treatment services, but low-quality whole-course management. Integration of medical and public health services should be strengthened to improve whole-course quality.

Inhibiting Glutaminase Exerts Opposite Effects on Ovariectomy-Induced and Age-Related Reductions in Murine Bone Mass.

Recent studies have provided links between glutamine metabolism and bone remodeling, but little is known about its role in primary osteoporosis progression. We aimed to determine the effects of inhibiting glutaminase (GLS) on two types of primary osteoporosis and elucidate the related metabolism. To address this issue, age-related and ovariectomy (OVX)-induced bone loss mouse models were used to study the in vivo effects of CB-839, a potent and selective GLS inhibitor, on bone mass and bone turnover. We also studied the metabolic profile changes related with aging and GLS inhibition in primary bone marrow stromal cells (BMSC) and that related with OVX and GLS inhibition in primary bone marrow-derived monocytes (BMM). Besides, we studied the possible metabolic processes mediating GLS blockade effects during aging-impaired osteogenic differentiation and RANKL-induced osteoclast differentiation respectively via in vitro rescue experiments. We found that inhibiting GLS via CB-839 prevented OVX-induced bone loss while aggravated age-related bone loss. Further investigations showed that effects of CB-839 treatment on bone mass were associated with alterations of bone turnover. Moreover, CB-839 treatment altered metabolic profile in different orientations between BMSC of aged mice and BMM of ovariectomized mice. In addition, rescue experiments revealed that different metabolic processes mediated glutaminase blockade effects between aging-impaired osteogenic differentiation and RANKL-induced osteoclast differentiation. Taken together, our data demonstrated the different outcomes caused by CB-839 treatment between two types of osteoporosis in mice, which were tightly connected to the suppressive effects on both aging-impaired osteoblastogenesis and OVX-enhanced osteoclastogenesis mediated by different metabolic processes downstream of glutaminolysis.

Supporting and retaining competent primary care workforce in low-resource settings: lessons learned from a prospective cohort study.

OBJECTIVE: Assess whether local health facilities can adequately support the performance of general practitioners (GPs) trained by China's national compulsory services programme (CSP). DESIGN: Prospective cohort study. SETTING: Health facilities in middle and western rural areas in China, 2015-2022. PARTICIPANTS: Cohorts of CSP graduates from 2015 to 2019 in four major medical universities. MAIN OUTCOMES: Job performance measured by a 12-item Job Performance Scale; productivity measured by outpatient volume per day; turnover measured by ever changing jobs within the past year. RESULTS: 91.2%, 92.0% and 90.5% GPs working in township health centres reported inadequate medication, equipment and external assistance from higher level hospitals, while CSP graduates working in secondary or tertiary hospitals reported a lower rate of less than 60%. The top three tests reported as lacking were blood gases (67.7%), microbiology (61.6%) and cancer biomarkers (49.7%); the top three lacked procedures were CT scan (64.8%), MRI scan (58.1%) and ambulatory BP monitoring (55.8%); and the top three lacked drugs were drugs for cardiovascular diseases (23.3%), systematic hormonal preparations (17.7%) and traditional Chinese medicines (13.0%). Multivariable analysis showed that facility support was positively associated with job performance-adequate medication increased job performance by 2.2 points (95% CI 0.7 to 3.8), and adequate external assistance increased job performance by 3.3 points (95% CI 1.8 to 4.8). Facility support was also positively associated with productivity-adequate medication increased outpatients seen per day by 20% (95% CI 0.1 to 0.3), and adequate equipment increased outpatients seen per day by 12% (95% CI 0.0 to 0.2). Facility support did not have significant impact on turnover, but GPs who changed jobs in the past year were 1.9-2.3 times more likely to report adequate facility support. CONCLUSION: GPs in township health centres experienced a high prevalence of shortage in facility support. The identification of a positive association between facility support and performance and productivity has implications for future research and resources deployment in primary healthcare.

Prevalence of self-reported chronic conditions and poor health among older adults with and without vision impairment in China: a nationally representative cross-sectional survey.

OBJECTIVE: To examine the self-reported prevalence of 13 chronic conditions and poor health among Chinese adults aged 45 years and older with and without self-reported vision impairment. DESIGN: Cross-sectional study from the China Health and Retirement Longitudinal Study 2018, a nationally representative survey of Chinese adults aged 45 years and older involving 19 374 participants. METHODS: We used logistic regression to assess the association between vision impairment and 13 common chronic conditions and between vision impairment and poor health for those with any of these chronic conditions. RESULTS: Older people with self-reported vision impairment were significantly more likely to report all 13 chronic conditions (all p<0·05). After controlling for age, gender, education, residential status (rural vs urban), smoking and BMI, the highest adjusted odds were for hearing impairment (OR=4.00 (95% CI 3·60 to 4·44]) and depression (OR=2.28 (95% CI 2.06 to 2.51)). The lowest risk, though still significant, was for diabetes (OR=1·33 (95% CI 1.11 to 2.05)) and hypertension (OR=1.20 (95% CI 1.04 to 1.38)). After controlling for these potential confounding factors, among older people with chronic conditions, those with vision impairment were 2.20 to 4.04 times more likely to have poor health, compared with those without vision impairment (all p<0.001), with the exception of cancer (p=0.595). CONCLUSIONS: Higher prevalence of chronic conditions is strongly associated with vision impairment among older Chinese adults and poor health is strongly associated with vision impairment among people with chronic conditions.

Urban-rural disparities in hypertension prevalence, awareness, treatment, and control among Chinese middle-aged and older adults from 2011 to 2015: a repeated cross-sectional study.

BACKGROUND: China has experienced a continuing increase in hypertension prevalence over the past few decades, especially in rural areas. The paper aims to examine the variation of urban-rural disparities in hypertension prevalence, awareness, treatment, and control among Chinese middle-aged and older adults between 2011 and 2015. METHODS: Our team extracted data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative survey of residents aged 45 years and older. In this study, we used the 2011 wave and the 2015 wave of CHARLS. We calculated crude rates and age-adjusted rates of hypertension prevalence, awareness, treatment, and control for the general, urban, and rural populations in each wave and performed chi-square tests to examine urban-rural disparities. We used logistic regression to further confirm these disparities by controlling confounding factors in each wave. We then used generalized estimating equation (GEE) to further examine whether urban-rural disparities changed between 2011 and 2015. RESULTS: We included 11,129 records in the 2011 wave and 8916 records in the 2015 wave in this study. The mean age was 59.0 years and 5359 (48.2%) participants were male in the 2011 wave. Age-adjusted hypertension prevalence, awareness, treatment, control, and control among treated in the total population were 38.5%, 70.6%, 59.2%, 27.4%, and 46.4% in 2015. Urban-rural disparities in the indicators mentioned above were 5.7%, 13.4%, 15.3%, 9.4% and 5.6% in 2011; which decreased to 4.8%, 2.7%, 5.2%, 4.9% and 3.8% in 2015. Urban-rural disparities in prevalence, awareness and treatment were statistically significant in 2011 but not significant in 2015 adjusted for confounding factors, yet control disparities were statistically significant in both waves. Finally, urban-rural disparities in awareness and treatment had narrowed from 2011 to 2015. CONCLUSIONS: Awareness, treatment, and control rates were sub-optimal among both urban and rural adults. Prevention and management of hypertension among both urban and rural adults should be further strengthened. Awareness and treatment increased more rapidly among rural adults, indicating some achievement had been made in enhancing the healthcare system in rural areas. More efforts are needed in attaining urban-rural equity of healthcare services.

Mitochondrial pyruvate carrier blockade results in decreased osteoclastogenesis and bone resorption via regulating mitochondrial energy production.

It's widely accepted that increasing mitochondrial respiration plays a pivotal role during osteoclastogenesis. Mitochondrial pyruvate carrier (MPC) is the key transporter that links glycolysis to mitochondrial respiration but little is known about its role during osteoclastogenesis. Our goal was to determine the effects of its blockade on osteoclastogenesis and bone resorption in vivo and in vitro. To address this issue, we performed gene knockdown or pharmacologically inhibited MPC in primary bone marrow-derived monocytes (BMMs) or in an ovariectomized mouse model. We also studied the metabolic changes in RANKL-induced differentiating BMMs with MPC blockade and performed rescue experiments. We found that MPC blockade resulted in decreased osteoclastogenesis both in vivo and in vitro and inhibiting MPC significantly alleviated ovariectomy-induced trabecular bone loss. Further investigations showed that MPC blockade significantly reversed the metabolic profile related to RANK activation, including decreased intermediates involved in citric acid cycle and glutamine metabolism. Moreover, metabolic flux analysis verified that MPC blockade decreased pyruvate flux into TCA cycle with no significant effect on glycolysis. Besides, MPC blockade resulted in suppressed mitochondrial biogenesis in addition to oxidative phosphorylation. Rescue experiments revealed that inhibiting pyruvate dehydrogenase kinase (PDK) via sodium dichloroacetate (DCA), but not targeting glutamine metabolism, could reverse the effects of MPC blockade on osteoclastogenesis. These implied that the effects of MPC blockade were mediated by reduced pyruvate fuel into citric acid cycle in multiple aspects. Taken together, our data demonstrated the inhibitory effects of MPC blockade on osteoclastogenesis, which was mediated by decreased mitochondrial energy production.

An Injectable Hydrogel Scaffold Loaded with Dual-Drug/Sustained-Release PLGA Microspheres for the Regulation of Macrophage Polarization in the Treatment of Intervertebral Disc Degeneration.

Due to the unique physical characteristics of intervertebral disc degeneration (IVDD) and the pathological microenvironment that it creates, including inflammation and oxidative stress, effective self-repair is impossible. During the process of intervertebral disc degeneration, there is an increase in the infiltration of M1 macrophages and the secretion of proinflammatory cytokines. Here, we designed a novel injectable composite hydrogel scaffold: an oligo [poly (ethylene glycol) fumarate]/sodium methacrylate (OPF/SMA) hydrogel scaffold loaded with dual-drug/sustained-release PLGA microspheres containing IL-4 (IL-4-PLGA) and kartogenin (KGN-PLGA). This scaffold exhibited good mechanical properties and low immunogenicity while also promoting the sustained release of drugs. By virtue of the PLGA microspheres loaded with IL-4 (IL-4-PLGA), the composite hydrogel scaffold induced macrophages to transition from the M1 phenotype into the M2 phenotype during the early induced phase and simultaneously exhibited a continuous anti-inflammatory effect through the PLGA microspheres loaded with kartogenin (KGN-PLGA). Furthermore, we investigated the mechanisms underlying the immunomodulatory and anti-inflammatory effects of the composite hydrogel scaffold. We found that the scaffold promoted cell proliferation and improved cell viability in vitro. While ensuring mechanical strength, this composite hydrogel scaffold regulated the local inflammatory microenvironment and continuously repaired tissue in the nucleus pulposus via the sequential release of drugs in vivo. When degenerative intervertebral discs in a rat model were injected with the scaffold, there was an increase in the proportion of M2 macrophages in the inflammatory environment and higher expression levels of type II collagen and aggrecan; this was accompanied by reduced levels of MMP13 expression, thus exhibiting long-term anti-inflammatory effects. Our research provides a new strategy for promoting intervertebral disc tissue regeneration and a range of other inflammatory diseases.

Prediction Models for Prognosis of Cervical Cancer: Systematic Review and Critical Appraisal.

Objective: This work aims to systematically identify, describe, and appraise all prognostic models for cervical cancer and provide a reference for clinical practice and future research. Methods: We systematically searched PubMed, EMBASE, and Cochrane library databases up to December 2020 and included studies developing, validating, or updating a prognostic model for cervical cancer. Two reviewers extracted information based on the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies checklist and assessed the risk of bias using the Prediction model Risk Of Bias ASsessment Tool. Results: Fifty-six eligible articles were identified, describing the development of 77 prognostic models and 27 external validation efforts. The 77 prognostic models focused on three types of cervical cancer patients at different stages, i.e., patients with early-stage cervical cancer (n = 29; 38%), patients with locally advanced cervical cancer (n = 27; 35%), and all-stage cervical cancer patients (n = 21; 27%). Among the 77 models, the most frequently used predictors were lymph node status (n = 57; 74%), the International Federation of Gynecology and Obstetrics stage (n = 42; 55%), histological types (n = 38; 49%), and tumor size (n = 37; 48%). The number of models that applied internal validation, presented a full equation, and assessed model calibration was 52 (68%), 16 (21%), and 45 (58%), respectively. Twenty-four models were externally validated, among which three were validated twice. None of the models were assessed with an overall low risk of bias. The Prediction Model of Failure in Locally Advanced Cervical Cancer model was externally validated twice, with acceptable performance, and seemed to be the most reliable. Conclusions: Methodological details including internal validation, sample size, and handling of missing data need to be emphasized on, and external validation is needed to facilitate the application and generalization of models for cervical cancer.