Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

Background/Aims: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). Methods: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. Results: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21–0.81). Conclusions Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.

Humans ; Thyroid Neoplasms/surgery* ; Thyroid Cancer, Papillary

Buruli ulcer (BU), caused by

OBJECTIVE：To provide reference for clinical decision-making related to chemotherapy-induced nausea and vomiting（CINV）. METHODS ：The medical records of patients diagnosed as malignant tumor receiving multi-day cisplatin-containing chemotherapy in our hospital were collected by hospital information system from Jan.-Dec. 2012. The medical records were divided into tropisetron group ，ramosetron group and palonosetron group according to different schemes of 5-hydroxytryptamine-3 receptor antagonist. The covariates of 3 groups were balanced by propensity score matching method ；cost-utility analysis was conducted for the 3 matched antiemetic schemes ；one-way sensitivity analysis and sampling uncertainty analysis were also conducted. RESULTS ： The results of cost-utility analysis showed that treatment cost of one observation period of tropisetron group was 237.71 yuan and utility were 0.054 68 QALYs；that of ramosetron group was 242.37 yuan and utility were 0.055 26 QALYs，and that of palonosetron group was 319.24 yuan and utility were 0.055 76 QALYs. Compared with tropisetron group ，the ICER of palonosetron group was 75 155.69 yuan/QALY；Compared with ramosetron group ，the ICER of palonosetron group was 152 062.07 yuan/QALY. Both of them were lower than 3 times of China ’s 2020 per capita GDP （217 341 yuan/QALY）. The results of sensitivity analysis and sampling uncertainty analysis demonstrated that the results of basic analysis were robust. CONCLUSIONS ：Under the current drug price，the antiemetic regimen based on palonosetron is more economical for the prevention of CINV caused by multi-day chemotherapy containing cisplatin.

Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.
Animals ; Disease Models, Animal ; Female ; Gene Editing ; Humans ; Lamin Type A/metabolism* ; Macaca fascicularis ; Progeria/pathology*

The purification of parasite-infected erythrocytes from whole blood containing leucocytes is crucial for many downstream genetic and molecular assays in parasitology. Current methodologies to achieve this are often costly and time consuming. Here, we demonstrate the successful application of a cheap and simple Non-Woven Fabric (NWF) filter for the purification of parasitized red blood cells from whole blood. NWF filtration was applied to the malaria-parasitized blood of three strains of mice, and one strain of rat, and to Babesia gibsoni parasitized dog blood. Before and after filtration, the white blood cell (WBC) removal rates and red blood cell (RBC) recovery rates were measured. After NWF filter treatment of rodent malaria-infected blood, the WBC removal rates and RBC recovery rates were, for Kunming mice: 99.51%±0.30% and 86.12%±8.37%; for BALB/C mice: 99.61%±0.15% and 80.74%±7.11%; for C57 mice: 99.71%±0.12% and 84.87%±3.83%; for Sprague-Dawley rats: 99.93%±0.03% and 83.30%±2.96%. Microscopy showed WBCs were efficiently removed from infected dog blood samples, and there was no obvious morphological change of B. gibsoni parasites. NWF filters efficiently remove leukocytes from malaria parasite-infected mouse and rat blood, and are also suitable for filtration of B. gibsoni-infected dog blood.

ABSTRACT OBJECTIVE：To investigate the present situation of clinical pharmacy in different levels of medical institutions in Chongqing，and to investigate the method for optimizing clinical pharmaceutical care. METHODS：By questionnaire survey，50 sample medical institutions（including 15 third level hospitals，25 second level hospitals and 10 first level hospitals）in Chongqing were selected according to the region，the level of medical institutions，comprehensive and specialized hospitals. The team of clinical pharmacists and the development of clinical pharmacy were investigated，and the results were statistically analyzed to find common problems and put forward relevant suggestions. RESULTS & CONCLUSIONS：Totally 45 questionnaires were collected， with a recovery rate of 90％，of which 39 questionnaires were qualified，with a qualified rate of 86.67％. There were 32 hospitals （82.05％）in 39 medical institutions with clinical pharmacy departments and 4 hospitals（10.26％）with clinical pharmacist training base. There were 239 full-time pharmacists in 39 medical institutions，with an average of 6.13 persons in each medical institution， including 4.5 full-time clinical pharmacists，and 2-5 full-time clinical pharmacists（25 hospitals）in most medical institutions. Top 5 clinical departments that clinical pharmacists mainly participated in were respiratory department，cardiovascular department， endocrinology department，ICU and oncology department. Most of the clinical pharmacists（16 hospitals，42.11％）worked in the clinic for more than 50％ to no more than 80％. The number of medical institutions（28-37，＞70.00％）carrying out ADR monitoring， rational drug use knowledge publicity， prescription and medical order comment， ward round， consultation， editing and publishing drug information was relatively high. 28 medical institutions（78.95％）did not carry out the test of therapeutic drugs；39（100％）medical institutions had carried out the education of patients’drug use，in the form of billboards（30 hospitals，78.95％），science lectures（28 hospitals，73.68％）and drug education forms（28 hospitals，73.68％）The contents of drug use education mainly included precautions（39 hospitals，100％），usage and dosage（37 hospitals，97.37％）， ADR（36 hospitals，94.74％）. 29 hospitals had carried out clinical pharmaceutical research（73.68％），mainly rational drug use research（28 hospitals，73.68％）；5 medical institutions（12.82％）had set up joint pharmacy outpatient service，2（5.12％）had set up independent pharmacy outpatient service，the rest had not set up pharmacy outpatient service（26 hospitals，66.67％）. In this survey，it is found that there are some problems，such as incomplete coverage of beds in the ward in pharmaceutical care，weak foundation of scientific research in pharmaceutical departments. It is suggested that the national and local health committees should strengthen the construction of multi-level clinical pharmacy talent echelon，explore and train resident clinical pharmacists，select and build key clinical pharmacy specialties in Chongqing，and establish incentive mechanism for clinical pharmacists. Medical institutions at all levels can adopt multiple ways to accelerate the training of clinical pharmacists，increase the publicity of pharmacists’outpatient service，change the working mode of the ward，cultivate special clinical pharmacists，improve the ways and paths of continuing education，and enhance the strength of scientific research to improve the level of clinical pharmaceutical care.

High-quality data are the foundation to monitor the progress and evaluate the effects of road traffic injury prevention measures. Unfortunately, official road traffic injury statistics delivered by governments worldwide, are often believed somewhat unreliable and invalid. We summarized the reported problems concerning the road traffic injury statistics through systematically searching and reviewing the literature. The problems include absence of regular data, under-reporting, low specificity, distorted cause spectrum of road traffic injury, inconsistency, inaccessibility, and delay of data release. We also explored the mechanisms behind the problematic data and proposed the solutions to the addressed challenges for road traffic statistics.
Accidental Injuries ; epidemiology ; prevention & control ; Accidents, Traffic ; prevention & control ; statistics & numerical data ; Global Health ; Humans

We sought to identify the differences between adolescents left behind in their home villages/towns (LBA) and non-left behind adolescents (NLB) on subjective well-being and family functioning due to parental migration in south China. We used a stratified cluster sampling method to recruit middle school students in a city experiencing population-emigration in Jiangxi Province in 2010. Participants included adolescents from families with: (1) one migrant parent, (2) both parents who migrated, or (3) non-left behind adolescents (i.e., no migrant parent). To determine predictors of subjective well-being, we used structural equation models. Adolescents left behind by both parents (LBB) were less likely to express life satisfaction (P = 0.038) in terms of their environments (P = 0.011) compared with NLB. A parent or parents who migrated predicts lower subjective well-being of adolescents (P = 0.051) and also lower academic performance. Being apart from their parents may affect family functioning negatively from an adolescent's viewpoint. Given the hundreds of millions of persons in China, many who are parents, migrating for work, there may be mental health challenges in some of the adolescents left behind.
Adolescent ; Aging ; China ; Emigration and Immigration ; Female ; Humans ; Male ; Mental Health ; statistics & numerical data ; Parent-Child Relations ; Parents ; Psychology, Adolescent ; Rural Population ; Socioeconomic Factors ; Surveys and Questionnaires ; Transients and Migrants