Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

To address the challenges of capturing micro-strains in detecting esophageal motility disorders and the limitations of existing high-resolution manometry and functional intraluminal imaging probes in directly measuring esophageal tissue electrical impedance, this study proposes a novel flexible balloon sensor structure that integrates a piezoelectric film assembly with a distributed impedance electrode array. Using the electrical analysis module in the finite element analysis (FEA) software, simulations of the forward problem for esophageal impedance detection were conducted to optimize the excitation source parameters, and a physical prototype was fabricated. Under a relative excitation mode with a voltage sensitivity of 2.059%, the voltage output characteristics of the impedance electrode array were analyzed during linear changes in the balloon filling volume. Based on the performance variation of the piezoelectric film assembly, 80% was selected as the optimal filling volume. Force-electric coupling tests were conducted on the balloon sensor using a pressure testing platform, revealing that both the piezoelectric film assembly inside the balloon and the impedance electrodes outside the balloon exhibited significant load differentiation characteristics as the force application point shifted. In summary, this balloon sensor facilitates the localization of force application while simultaneously analyzing esophageal tissue properties, offering a novel diagnostic approach and objective tool for esophageal disease detection.
Esophagus/physiology* ; Electric Impedance ; Humans ; Finite Element Analysis ; Manometry/methods* ; Electrodes ; Esophageal Motility Disorders/physiopathology* ; Equipment Design

Objective:To investigate the radioactivity levels and variation trends of 90Sr in drinking water and food around the Qinshan Nuclear Power Plant in operation. Methods:From 2012 to 2022, the source, factory, and tap water was collected within 30 km around the Qinshan Nuclear Power Plant during the wet and dry seasons (i.e., May and October, respectively) each year to determine the 90Sr concentration in water. According to the dietary habits of local residents, four kinds of food, including rice, cabbage, mullet, and crucian carp, were collected to determine and analyze the 90Sr radioactivity concentration in food using the bis-(2-ethylhexyl) phosphoric acid extraction chromatographic method. Results:From 2012 to 2022, the 90Sr radioactivity concentrations in the source, factory, and tap water around the Qinshan Nuclear Power Plant ranged from 3.73 to 11.89 mBq/L, 2.95 to 9.83 mBq/L, and 3.12 to 8.70 mBq/L, respectively, showing nonsignificant fluctuations over the years. The 90Sr radioactivity concentrations in rice, cabbage, mullet, and crucian carp ranged from 0.02 to 0.46 Bq/kg (dry weight), 0.26 to 1.07 Bq/kg (fresh weight), 0.38 to 1.05 Bq/kg (fresh weight), and 0.08 to 1.32 Bq/kg (fresh weight), respectively, all below the national standard limits. Conclusions:From 2012 to 2022, the 90Sr radioactivity levels in drinking water and food around the Qinshan Nuclear Power Plant were at the background level and remained stable.

Objective:To explore the genetic diversity of Mycobacterium tuberculosis (MTB) in different types of tuberculosis and its association with clinical features, providing evidence for precise diagnosis and treatment of tuberculosis. Methods:This cross-sectional study included 103 cases of tuberculosis (38 with simple pulmonary tuberculosis, 43 with tuberculous pleurisy, and 22 with pulmonary combined with extrapulmonary tuberculosis) from Shenzhen Third People′s Hospital from 2015 to 2018. Paired bacterial strains from lung and pleural effusion/extrapulmonary sites were collected. Whole-genome sequencing (WGS) was used for drug resistance prediction, and genetic diversity (π value) was calculated as well as differential genes screening. Statistical analysis included paired t-tests and χ2 tests to compare clinical, bacteriological and genetic diversity features among groups.Results:The simple pulmonary tuberculosis group exhibited significantly higher rates of retreatment (71.7%, 27/38), cavitation (70.4%, 19/27), and multidrug-resistant or rifampicin-resistant (MDR/RR) (60.5%, 23/38) compared to the tuberculous pleurisy group (retreatment 11.9%, 5/42; cavitation 11.9%, 5/42; MDR/RR 16.3%, 7/43) and extrapulmonary tuberculosis group (retreatment 9.1%, 2/22; cavitation 18.2%, 4/22; MDR/RR 13.6%, 3/22) ( P<0.05). The overall π values of the MTB strain genomes in lung [(5.94±3.93)×10 ?5], pleural effusion[(6.22±3.51)×10 ?5], and extrapulmonary tissues [(5.83±3.54)×10 ?5] showed no significant differences ( H=0.10, P=0.94). Differential gene diversity analysis revealed that π value alternating genes related to respiration and intermediate metabolism were prominently high [tuberculous pleurisy 32.4% (11/34) and extrapulmonary tuberculosis groups 31.4% (32/102)], while cell wall-associated genes dominated in the simple pulmonary tuberculosis group (42.9%, 6/14). Drug resistance profiles and mutation spectra were identical across isolates from different sites within the same patient. Conclusion:WGS revealed the MTB diversity among different types of tuberculosis. Difference between pulmonary and extrapulmonary environments may impel the adaptive alternations of the bacterial strains to maintain survival with higher overall genome stability. Drug resistance testing of lung-derived isolates may provide references on extrapulmonary tuberculosis treatment.

Circadian rhythm refers to the 24-hour periodic changes in behavior, physiology, and molecular processes in the human body. Disruptions to the circadian rhythm not only affect mental health but are also associated with various metabolic disorders, including the regulation of bone and muscle metabolism. Research has shown that work-related musculoskeletal disorders (WMSDs) are influenced not only by workload but also by circadian rhythm factors, such as shift work. This review examined the relationships between circadian rhythm-related antecedents, outcomes, and WMSDs, exploring their shared metabolic markers and mechanisms. It provided a systematic overview of the intrinsic connection between circadian rhythm disruptions and WMSDs. While current studies highlight the impact of circadian rhythm disturbances on musculoskeletal disorders, further investigation is required to address the confounding factors involved. Future research should integrate chronobiology with both subjective and objective data to explore the pathway from environmental factors to intermediate phenotypes to diseases, ultimately providing a more comprehensive understanding of the network mechanisms underlying WMSDs.

ObjectiveIn the realm of forensic science, dust is a valuable type of trace evidence with immense potential for intricate investigations. With the development of DNA sequencing technologies, there is a heightened interest among researchers in unraveling the complex tapestry of microbial communities found within dust samples. Furthermore, striking disparities in the microbial community composition have been noted among dust samples from diverse geographical regions, heralding new possibilities for geographical inference based on microbial DNA analysis. The pivotal role of microbial community data from dust in geographical inference is significant, underscoring its critical importance within the field of forensic science. This study aims to delve deeply into the nuances of fungal community composition across the urban landscapes of Beijing, Fuzhou, Kunming, and Urumqi in China. It evaluates the accuracy of biogeographic inference facilitated by the internal transcribed spacer 2 (ITS2) fungal sequencing while concurrently laying a robust foundation for the operational integration of environmental DNA into geographical inference mechanisms. MethodsITS2 region of the fungal genomes was amplified using universal primers known as 5.8S-Fun/ITS4-Fun, and the resulting DNA fragments were sequenced on the Illumina MiSeq FGx platform. Non-metric multidimensional scaling analysis (NMDS) was employed to visually represent the differences between samples, while analysis of similarities (ANOSIM) and permutational multivariate analysis of variance (PERMANOVA) were utilized to statistically evaluate the dissimilarities in community composition across samples. Furthermore, using Linear Discriminant Analysis Effect Size (LEfSe) analysis to identify and filter out species that exhibit significant differences between various cities. In addition, we leveraged SourceTracker to predict the geographic origins of the dust samples. ResultsAmong the four cities of Beijing, Fuzhou, Kunming and Urumqi, Beijing has the highest species richness. The results of species annotation showed that there were significant differences in the species composition and relative abundance of fungal communities in the four cities. NMDS analysis revealed distinct clustering patterns of samples based on their biogeographic origins in multidimensional space. Samples from the same city exhibited clear clustering, while samples from different cities showed separation along the first axis. The results from ANOSIM and PERMANOVA confirmed the significant differences in fungal community composition between the four cities, with the most pronounced distinctions observed between Fuzhou and Urumqi. Notably, the biogeographic origins of all known dust samples were successfully predicted. ConclusionSignificant differences are observed in the fungal species composition and relative abundance among the cities of Beijing, Fuzhou, Kunming, and Urumqi. Employing fungal ITS2 sequencing on dust samples from these urban areas enables accurate inference of biogeographical locations. The high feasibility of utilizing fungal community data in dust for biogeographical inferences holds particular promise in the field of forensic science.

Gastrointestinal dysfunction is a common and significant complication in colorectal surgical practice, which is associated with gut microbiota dysbiosis caused by various perioperative interventions. Currently, enhanced recovery after surgery (ERAS) protocols have been increasingly adopted in clinical practice, greatly accelerating the recovery of postoperative intestinal function. However, there are still no effective interventions in the ERAS protocols to target surgery-induced gut microbiota dysbiosis. Probiotics, as a key treatment method targeting the gut microbiota, can stimulate intestinal motility, inhibit the colonization of pathogenic bacteria, enhance intestinal barrier function, among other effects. Based on these effects of probiotics, they are expected to resolve the neglected gut microbiota dysbiosis, further accelerating the postoperative recovery of intestinal function after colorectal surgery. This article reviews the mechanisms and clinical progress in postoperative bowel functional recovery after colorectal surgery.

Objective To investigate the application effect of three-dimensional CT-assisted pedicle measurement in elderly patients undergoing percutaneous vertebroplasty(PVP).Methods A total of 80 osteoporotic patients with L1 vertebral compression fracture who were treated in People's Hospital of Qujiang District in Shaoguan from March 2021 to March 2023 were selected as the study subjects.Three-dimensional CT-assisted pedicle measurement was performed before surgery,including L1 axial effective angle,axial effective pedicle transverse,oblique sagittal effective angle,oblique sagittal effective longitudinal diameter,and pedicle transverse diameter,and their differences between different genders were analyzed.Four patients with an effective pedicle diameter of less than 3 mm were included into the bilateral group,and the rest of the patients were divided into the unilateral group(received unilateral-approach PVP)and the bilateral group(received bilateral-approach PVP)according to the random number table method.The perioperative conditions of patients in the two groups were collected.The follow-up was performed for six months after surgery,and the visual analogue scale(VAS)score and Oswestry dysfunction index(ODI)score of patients between the two groups were compared before surgery,1 month after surgery and 6 months after surgery.X-ray examinations were performed before and after surgery to evaluate the recovery of Cobb angle and cement leakage.Results No significant difference was observed in axial universal effective angle or universal oblique sagittal effective angles between genders(P>0.05).The male patients showed greater axial lateral effective angle,axial lateral effective pedicle transverse,axial universal effective pedicle transverse,lateral oblique sagittal effective angle,lateral oblique sagittal effective longitudinal diameter,universal oblique sagittal effective longitudinal diameter,and pedicle transverse as compared to female patients,with statistically significant differences(P<0.05).The intraoperative fluoroscopy times and bone cement injection volume of patients in the unilateral group were less/lower than those in the bilateral group,with statistically significant differences(P<0.05).There was no significant difference in the operation time of patients between the two groups(P>0.05).During the follow-up period,3 patients were lost to follow-up in the unilateral group and 4 patients in the bilateral group.One patient in the unilateral group had cement leakage.There were no significant differences in the VAS scores,ODI scores before surgery and 1 month after surgery or Cobb angles before and after surgery between the two groups(P>0.05).The VAS and ODI scores of patients in the unilateral group 6 months after surgery were significantly higher than those in the bilateral group,with statistically significant differences(P<0.05).Conclusion In the treatment of osteoporotic vertebral compression fractures,three-dimensional CT-assisted pedicle measurement before PVP can help to achieve accurate puncture,and improve the safety and effectiveness of the surgery.

On January 1,2022,the China International Association for the Promotion of Science and Technology(CIAPST)officially implemented two pivotal standards:Quality Standards for Medical Germanium-68/Gallium-68(68 Ge/68 Ga)Generators and Gallium-68 Radiopharmaceuticals(T/CI 046-2021)and Quality Standards for Medical Lutetium-177(177 Lu)and Its Radiopharmaceuticals(T/CI 047-2021).These standards introduce innovative requirements for quality control and clinical application of radiopharmaceuticals,marking a significant advancement in China's regulatory framework for nuclear medicine.This article provides a compre-hensive analysis of the technical rationale,QC protocols,and clinical implications outlined in the standards.Against the backdrop of China's evolving nuclear medicine landscape,we further identify challenges in imple-mentation(e.g.,production consistency,regulatory compliance)and propose actionable strategies to optimize radiopharmaceutical quality management systems.Our perspective aims to support the standardization and global integration of China's radiopharmaceutical industry.