Objective:To propose a novel refined subtyping of Neer type Ⅵ proximal humerus fracture-dislocation and explore its clinical application.Methods:A retrospective study was conducted to analyze the data of 36 patients who had been admitted to Department of Orthopaedics, Beijing Friendship Hospital between January 2018 and December 2022 for surgical treatment with proximal humeral internal locking system (PHILOS) for Neer type Ⅵ proximal humerus fracture-dislocation. There were 25 males and 11 females with an age of (46.1±4.7) years. According to the fracture-dislocation and the separation between the humeral head and the stem, the patients with Neer type Ⅵ proximal humerus fracture-dislocation were further subdivided into 3 subtype groups (known as STAB subtypes): subtype-T group (dislocation of the shoulder joint with macro-capitellar fracture, n=14), subtype-A group (proximal humerus fracture-dislocation without separation of the humeral head from the humeral stem, n=12), and subtype-B group (dislocation of the proximal humerus fracture with separation of the humeral head from the humeral stem, n=10). STAB subtyping was performed on the same imaging data from all the patients at admission and 2 weeks later by 4 surgeons with different qualifications. Interobserver and intraobserver agreements of the STAB typing were verified. The operation time, fracture healing time, visual analogue scale (VAS) pain score, Constant-Murley score, and complications were recorded for patients in the 3 subtype groups. Results:The differences in the preoperative general data were not statistically significant between the 3 subtype groups, indicating comparability ( P>0.05). All patients were followed up for (11.2±4.2) months. The inter-observer and intra-observer Kappa values for STAB subtyping were 0.94 and 0.95, respectively. For subtype-T group, subtype-A group, and subtype-B group, respectively, the operation time was (68.9±5.6) min, (90.0±5.2) min, and (113.0±9.2) min; the fracture healing time was (9.0±0.8) weeks, (10.3±1.2) weeks, and (11.8±0.9) weeks; the VAS scores at the last follow-up were 1.0(1.0, 2.0) points, 2.0(1.0, 2.0) points, 2.0(2.0, 3.0) points; the Constant-Murley scores at the last follow-up were (83.6±2.8) points, (74.5±3.0) points, and (62.7±5.5) points. The differences between the 3 subtype groups in the above items were statistically significant ( P<0.05). The overall success rate of closed reduction was 61.1% (22/36). In subtype-T, subtype-A, and subtype-B groups, respectively, the number of patients with successful closed reduction was 13, 7, and 2, while complications occurred in 2, 3, and 6 patients. The differences in closed reduction and complications among the 3 groups were statistically significant ( P<0.05). Conclusions:The STAB subtyping proposed in this study demonstrates strong intra- and inter-group consistency. Because the refined STAB subtyping can reveal differences among all the Neer type Ⅵ proximal humeral fractures and dislocations, it may provide more precise guidance for personalized clinical decision-making.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

OBJECTIVE To evaluate the cost-effectiveness of regorafenib in the treatment of hepatocellular carcinoma after failure of sorafenib from the perspective of Chinese health system. METHODS Based on a phase Ⅲ trial（RESORCE）， the partition survival model （PSM） and Markov model were constructed. The cycle was set as four weeks， the duration of the study lasted for lifetime， the annual discount rate was 5%. Drug cost data was obtained from yaozhi.com， other cost data were obtained from Anhui Provincial Medical Insurance Bureau and related literature， and utility values were obtained from literature. The incremental cost-effectiveness ratio （ICER） was used as the evaluation index， and the value of willingness to pay （WTP） was three times of China’s gross domestic product （GDP） per capita in 2022； one-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The incremental cost of regorafenib group versus placebo group in PSM and Markov model was 112 116.95 yuan and 96 617.19 yuan， respectively. The incremental effectiveness was 0.31 QALYs and 0.32 QALYs， respectively. The ICERs were 360 751.01 yuan/QALY and 301 114.45 yuan/QALY， which were both greater than the value of WTP； regorafenib was not cost-effective. Results of one-way sensitivity analysis showed that the utility of progression-free survival and progressive disease， the unit cost of regorafenib had the greatest influence on the results， but ICER was always greater than the WTP within the floating range of each parameter. Under the WTP of 3 times China’s per capita GDP in 2022， the probabilities of regorafenib with cost-effectiveness were 0.8% （PSM） and 11.4% （Markov）. CONCLUSIONS Under the WTP of 3 times the per capita GDP of China， regorafenib is not cost-effective in the treatment of hepatocellular carcinoma after failure of sorafenib treatment， compared with placebo.

Objective:To learn about the progress of prevention and control of drinking-water-borne endemic arsenic poisoning in Henan Province, and provide scientific basis for achieving the goal of eliminating high arsenic hazards as scheduled.Methods:From July to August 2019, in accordance with the requirements of the National Monitoring Program for Drinking-water-borne Endemic Arsenic Poisoning, a general survey was carried out in 26 high-arsenic villages in 6 counties of Henan Province to investigate the water improvement situation and the operation of water improvement projects, and the arsenic content in drinking water of households was measured, meanwhile, the arsenic poisoning status of permanent residents in high-arsenic villages was investigated.Results:All 26 villages with high arsenic content in the province had undergone water improvement, with a water improvement rate of 100.00%. A total of 18 water improvement projects were investigated in 26 high-arsenic villages, all of which were operating normally. Twenty-six water samples were collected, and the arsenic content in the household water was < 0.01 mg/L, which met the sanitary standards for drinking water. No patient of endemic arsenic poisoning was found during the survey.Conclusion:In Henan Province, the drinking-water-borne endemic arsenic poisoning has been effectively controlled, and the prevention and control achievements should continue to be consolidated in the future.

Objective:To compare the effects of anterograde elastic stable intramedullary nailing (ESIN-A), retrograde K-wires fixation (KW-R) and retrograde precision shaping of elastic stable intramedullary nailing (ESIN-RPS) in the treatment of fractures of distal radial metaphyseal diaphyseal junction (DRMDJ) in children.Methods:A retrospective study was conducted to analyze the data of 112 eligible children with DRMDJ fracture who had been treated at Department of Orthopedics, Children's Hospital, Anhui Medical University and Department of Orthopedics, The People's Hospital of Fuyang City,Anhui Medical University, from January 2016 to May 2022. There were 64 males and 48 females, with an age of (8.4±2.3) years. The children were divided into 3 groups according to different surgical fixation methods: group ESIN-A of 36 cases, group KW-R of 52 cases, and group ESIN-RPS of 24 cases. The operation time, intraoperative bleeding, fluoroscopy times, alignment rates and residual angulations by the anteroposterior and lateral X-ray films immediately after reduction were compared among the 3 groups. The Gartland-Werley evaluation of wrist function and complications were compared at the last follow-up.Results:There was no statistically significant difference in the preoperative general data among the 3 groups, indicating comparability ( P>0.05). In the operation time, group KW-R [(71.2±9.2) min] > group ESIN-A [(65.1±13.1) min] > group ESIN-RPS [(51.7±17.1) min]; in the fluoroscopy times, group KW-R [(13.9±6.3) times] > group ESIN-A [(9.0±2.8) times] > group ESIN-RPS [(6.4±2.0) times]; in the alignment rates by the anteroposterior and lateral X-ray films immediately after reduction, group ESIN-RPS (93.1%±4.6% and 95.2%±3.3%) > group KW-R (82.1%±11.0% and 88.1%±7.4%) > group ESIN-A (80.4%±9.9% and 86.7%±6.9%); in the residual angulations by the anteroposterior and lateral X-ray films immediately after reduction, group ESIN-RPS (3.3°±1.8° and 2.9°±2.1°) < group ESIN-A (5.2°±1.0° and 5.0°±3.2°) < group KW-R (6.6°±1.6°and 7.5°±2.7°). Pairwise comparisons in the above items were statistically significant ( P<0.05). In group ESIN-A, the incision length [(1.8±0.3) cm] was significantlylonger than that in group ESIN-RPS [(1.4±0.2) cm], and the intraoperative blood loss [(8.3±2.2) mL] significantly larger than that in group ESIN-RPS [(5.5±1.6) mL] ( P<0.05). One year after operation, the excellent and good rate by the Gartland-Werley evaluation of wrist function in groups ESIN-RPS, ESIN-A and KW-R, respectively, were 95.8% (23/24), 86.5% (31/36) and 86.1% (46/52), showing no statistically significant difference between the 3 group ( P>0.05), and the major incidence of complications in group KW-R (25.0%, 13/52) and in group ESIN-A (25.0%, 9/36) were significantly higher than that in group ESIN-RPS (4.2%, 1/24) ( P<0.05). Conclusion:In the treatment of DRMDJ fractures in children, compared with ESIN-A and KW-R, ESIN-RPS is an effective choice due to its advantages of shorter operation time, less intraoperative blood loss, less radiation, better alignment, and fewer complications.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals ; Humans ; Sarcopenia/metabolism* ; Forkhead Box Protein O3/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Primates/metabolism*

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Mice ; Animals ; Transcriptome ; Aging/metabolism* ; Cochlea ; Stria Vascularis ; Presbycusis

The construction of a countywide community for medical and health services is designed to upgrade the service capacity of primary medical and health institutions, to promote resource sharing and collaborative services, and promote the hierarchical medical system. Huzhou of Zhejiang province has launched its initiative in building a countywide community for medical services since 2018. The authors summarized its main practices in promoting the integration of the management system and optimizing operating mechanism of countywide medical and health institutions, promoting the reform of the county medical and health governance system, as well as the achievements and shortcomings, with a view to providing reference for promoting the high-quality development of the countywide medical and health service system.

OBJECTIVE: To investigate the short-term effectiveness of ultrasound-guided closed reduction by Kirschner wire provocation technique in the treatment of Salter-Harris types Ⅰ and Ⅱ periosteal entrapment of distal tibial epiphyseal fractures in children and adolescents. METHODS: Between May 2019 and May 2022, 41 patients with Salter Harris types Ⅰ and Ⅱ distal tibial epiphyseal fractures were admitted, all of whom had periosteal entrapment on preoperative MRI, and 38 cases (92.7%) were confirmed to have periosteal entrapment by intraoperative ultrasound. There were 24 males and 14 females, the age ranged from 6.8 to 15.7 years, with an average of 10.7 years; and there were 20 cases of Salter Harris type Ⅰ and 18 cases of type Ⅱ. The time from injury to operation was 22-76 hours, with an average of 28.4 hours. The preoperative imaging examination showed excellent alignment in 4 cases, good in 20 cases, and poor in 14 cases. The ultrasound guided Kirschner wire provocation technique for closed reduction and percutaneous Kirschner wire internal fixation were performed. The operation time, intraoperative fluoroscopy frequency, fracture healing time, and complications were recorded. Anteroposterior and lateral X-ray films of the affected ankle joint were taken before operation, at 3 months after operation, and at last follow-up to observe the healing of the fracture, and anteroposterior X-ray films of the whole length of both lower limbs were taken to evaluate the alignment of the force lines of the affected limbs. The range of motion (ROM), visual analogue scale (VAS) score, and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were used to evaluate ankle function. The mechanical lateral distal tibia angle (mLDTA) and the anatomic anterior distal tibia angle (aADTA) were measured. RESULTS: The operation time ranged from 17 to 52 minutes, with an average of 22.6 minutes, and the intraoperative fluoroscopy frequency ranged from 3 to 11 times, with an average of 4.2 times. X-ray examination during operation and at 2 days after operation showed that anatomical reduction was achieved. All patients were followed up 10-24 months, with an average of 16.4 months. All fractures healed in 6.1-7.2 weeks, with an average of 6.3 weeks; no fracture displacement occurred, and the patients recovered to their pre-injury level of motion at 6 months after operation. Needle tail irritation occurred in 2 cases at 4 weeks after operation, and they recovered after symptomatic treatment. During the follow-up, there was no serious complication such as incision deep infection, bone nonunion, delayed union, and malunion. At last follow-up, the patients' alignment were all excellent, and the difference was significant when compared with preoperative one ( Z=-7.471, P<0.001). The VAS score, AOFAS ankle-hindfoot score, dorsiflexion-plantar flexion ROM, varus-valgus ROM, mLDTA, and aADTA significantly improved at 3 months after operation and last follow-up when compared with preoperative ones ( P<0.05). CONCLUSION Ultrasound-guided closed reduction by Kirschner wire provocation technique for treating Salter-Harris types Ⅰ and Ⅱ periosteal entrapment of distal tibial epiphyseal fractures in children and adolescents is minimally invasive and safe.
Male ; Female ; Child ; Humans ; Adolescent ; Tibia ; Bone Wires ; Treatment Outcome ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods* ; Ultrasonography, Interventional ; Retrospective Studies ; Tibial Fractures/surgery*

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells