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

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*

The core problem of wound treatment is how to speed up healing. In recent years, the impact of wound microenvironment on healing has received increasing attention. Among the many factors affecting the wound microenvironment, wound bioelectric field and oxygen are crucial. At present, some new technologies based on microenvironmental factors including wound bioelectric field and oxygen to promote wound healing have been used in clinical practice. With further research development on the roles of wound bioelectric field and oxygen in wound healing and their mechanisms, a series of new technologies and products that regulate or create the most suitable wound microenvironment for healing including the bioelectric field of wound and oxygen will be produced, therefore providing effective means for precise wound treatment.

Objective:To explore the effects of B-cell lymphoma-2/adenovirus E1B 19 000 interacting protein 3 (BNIP3) on the migration and motility of human dermal microvascular endothelial cells (HDMECs) under hypoxia and the mechanism.Methods:The experimental research method was applied. (1) HDMECs were divided into normoxia group received routine culture and hypoxia 6, 12, 24 h groups treated under hypoxia with oxygen volume fraction of 2% for corresponding time according to the random number table (the same grouping method below). Western blotting was used to detect the protein expressions of BNIP3 and microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ) in HDMECs. (2) HDMECs were divided into normoxia+ unloaded group, normoxia+ BNIP3 knockdown group, hypoxia+ unloaded group, and hypoxia+ BNIP3 knockdown group which were transfected with unloaded virus or BNIP3 knockdown virus and were subjected to normoxic or hypoxic treatment. The BNIP3 protein expression was detected by Western blotting and immunofluorescence staining. The scratch area at 24 h post scratching was detected by scratch test, and the healing rate of scratch was calculated. The curve distance of cell movement was measured with the living cell workstation, and the speed of movement was calculated within 3 hours. (3) HDMECs were grouped and treated as experiment (2). Western blotting and immunofluorescence staining were performed to detect the protein expression of LC3Ⅱ. The number of sample was 3 in the above-mentioned experiments. Data were statistically analyzed with one-way analysis of variance and least significant difference test.Results:(1) Compared with those of normoxia group, the protein expressions of BNIP3 and LC3Ⅱ of cells in hypoxia 6, 12, 24 h groups were significantly increased ( P<0.01). (2) After 6 hours of culture, compared with that of hypoxia+ unloaded group, the BNIP3 protein expressions of cells in normoxia+ unloaded group and hypoxia+ BNIP3 knockdown group were significantly decreased ( P<0.05 or P<0.01). The red fluorescence denoting BNIP3 protein expression of cells in normoxia+ unloaded group and normoxia+ BNIP3 knockdown group was weak, the red fluorescence of cells in hypoxia+ unloaded group was strong, and the red fluorescence of cells in hypoxia+ BNIP3 knockdown group was significantly decreased compared with that in hypoxia+ unloaded group. After scratching for 24 hours, the scratch of cells in hypoxia+ unloaded group basically healed, while the remaining scratch area in the other three groups were large. The healing rates of scratch of cells in normoxia+ unloaded group, normoxia+ BNIP3 knockdown group, hypoxia+ unloaded group, and hypoxia+ BNIP3 knockdown group were (61±4)%, (58±4)%, (88±4)%, and (57±4)%, respectively. The healing rate of scratch of cells in hypoxia+ unloaded group was significantly higher than that in normoxia+ unloaded group ( P<0.01) and hypoxia+ BNIP3 knockdown group ( P<0.05). Within 3 hours of observation, the range of cell movement in hypoxia+ unloaded group was significantly larger than that in normoxia+ unloaded group, the range of cell movement in hypoxia+ BNIP3 knockdown group was significantly smaller than that in hypoxia+ unloaded group, and the curve movement velocity of cells in hypoxia+ unloaded group was significantly higher than that in normoxia+ unloaded group and hypoxia+ BNIP3 knockdown group ( P<0.01). (3) After 6 hours of culture, compared with hypoxia+ unloaded group, the LC3Ⅱ protein expressions of cells in hypoxia+ unloaded group and hypoxia+ BNIP3 knockdown group were decreased significantly ( P<0.05 or P<0.01). After 6 hours of culture, the red fluorescence denoting LC3 protein expressions of cells was weak in normoxia+ unloaded group and normoxia+ BNIP3 knockdown group, the red fluorescence of cells was significantly enhanced in hypoxia+ unloaded group, and the red fluorescence of cells was significantly inhibited in hypoxia+ BNIP3 knockdown group. Conclusions:BNIP3 can promote the migration and motility of HDMECs under hypoxia, and autophagy may be involved in the regulation migration of HDMECs by BNIP3.

Objective:To investigate the influencing factors and their predictive value of skin graft survival after Meek grafting in severe burn patients.Methods:A retrospective case-control study was conducted in 115 severe burn patients (95 males, 20 females, aged 1-74 years) who met the inclusion criteria and received Meek grafting in the First Affiliated Hospital of Army Medical University (the Third Military Medical University) from January 2013 to December 2019. The patients were divided into good skin graft survival group with skin graft survival rate≥70% (68 cases) and poor skin graft survival group with skin graft survival rate<70% (47 cases). The statistics of patients in the two groups were recorded during their first Meek grafting after admission including the gender, age, body mass index, full-thickness burn area, burn index, complication of inhalation injury, time from injury to operation, preoperative cystatin C level, preoperative albumin level, preoperative neutrophil, preoperative hemoglobin level, preoperative platelet count, and platelet count on the first, third, and fifth day after operation. The above indicators were statistically analyzed between the two groups with independent sample t test, Mann-Whitney U test, and chi-square test. A 1∶1 propensity score matching (PSM) of the gender, age, body mass index, full-thickness burn area, burn index, complication of inhalation injury, time from injury to operation of patients in the two groups were performed to eliminate the differences in baseline data, and then the above indicators of the remaining patients in the two groups were recorded and analyzed again. The indicators with statistically significant differences between the two groups after 1∶1 PSM were selected for multivariate logistic regression analysis to screen the independent risk factors affecting the skin graft survival after Meek grafting in severe burn patients. The receiver operating characteristic (ROC) curve of independent risk factors for predicting poor skin graft survival after Meek grafting in severe burn patients after 1∶1 PSM was drawn, and the area under the curve, the cut-off value, and the sensitivity and specificity under the cut-off value were calculated. The patients after 1∶1 PSM were divided into independent risk factor>the cut-off value group and independent risk factor≤the cut-off value group with the incidence of poor skin graft survival after Meek grafting compared using the chi-square test, and the relative risk of poor skin graft survival after Meek grafting was calculated. Results:Before 1∶1 PSM, there were no statistically significant differences in gender, age, body mass index, complication of inhalation injury, time from injury to operation, preoperative cystatin C level, preoperative albumin level, preoperative neutrophil, preoperative hemoglobin level of patients between the two groups ( P>0.05); the full-thickness burn area and burn index of patients in poor skin graft survival group were significantly higher than those in good skin graft survival group ( Z=-2.672, -2.882, P<0.01); the preoperative platelet count and the platelet count on the first, third, and fifth day after operation of patients in poor skin graft survival group were significantly lower than those in good skin graft survival group ( Z=-3.411, -3.050, -2.748, -2.686 , P<0.01). After 1∶1 PSM, 46 cases were remained in each group. There were no statistically significant differences in gender, age, body mass index, full-thickness burn area, burn index, complication of inhalation injury, time from injury to operation, preoperative cystatin C level, preoperative albumin level, preoperative neutrophil, preoperative hemoglobin level of remaining patients between the two groups ( P>0.05); the preoperative platelet count and the platelet count on the first, third, and fifth day after operation of patients in poor skin graft survival group were significantly lower than those in good skin graft survival group ( Z=-3.428, -2.940, t=-2.427, -2.316, P<0.05 or P<0.01). Multivariate logistic regression analysis showed that the preoperative platelet count was the only independent risk factor affecting the skin graft survival after Meek grafting in severe burn patients (odds ratio=0.994, 95% confidence interval=0.989-0.998, P<0.01). The area under the ROC curve of preoperative platelet count predicting poor skin graft survival after Meek grafting in 92 patients was 0.707 (95% confidence interval=0.603-0.798, P<0.01), and the cut-off value of preoperative platelet count was 98×10 9/L, with sensitivity of 54.3% and specificity of 78.3% under the cut-off value. The incidence of poor skin survival after Meek grafting of patients in preoperative platelet count≤98×10 9/L group was 71.4% (25/35), which was obviously higher than 36.8% (21/57) in preoperative platelet count>98×10 9/L group ( χ2=10.376, P<0.01). Compared with that in preoperative platelet count>98×10 9/L group, patients in preoperative platelet count≤98×10 9/L group had a relative risk of poor skin graft survival after Meek grafting of 2.211 (95% confidence interval=1.263-3.870). Conclusions:Preoperative platelet count is an independent risk factor affecting the skin graft survival after Meek grafting in severe burn patients and has a good predictive value. Meek grafting should be performed with caution when the preoperative platelet count of patients is≤98×10 9/L.

Objective: To analyze the epidemiological characteristics of HIV/AIDS infected students in Shandong Province, to provide a basis for the prevention and control of AIDS transmission in the student population. Methods: All 863 HIV/AIDS students cases during 2010-2019 were collected in Shandong Province. Epidemiological characteristics was described and the trends in the 10 years since 2010 was analyzed. Results: These 863 HIV/AIDS students were mainly transmitted through homosexual sex (763 cases, 88.41%), and the samples were mainly from voluntary consultation testing (433 cases, 50.17%). From 2010 to 2019, the proportion of student cases in the total number of cases showed an increasing trend ( χ 2 trend =30.21, P <0.01). Among them, the proportion of homosexual transmission cases increased year by year ( χ 2 trend =6.35, P =0.01), the proportion of cases aged 18-22 years increased year by year ( χ 2 trend =6.10, P =0.01), the proportion of cases with college degree or above increased year by year ( χ 2 trend =4.26, P =0.04). At present, voluntary consultation testing were the main source.There was no significant difference between the years of sample sources ( χ 2 trend =2.97, P =0.09). Conclusion The report number of students in Shandong Province are on the rise in recent years, especially those infected by same sex transmission, mainly with high education background, which calls for targeted strategies and intervention measures.

Organ damage is currently the leading cause of death directly hindering the further improvement of cure rate of severe burn patients. This paper introduces some thoughts on the comprehensive prevention and treatment of organ damage after severe burns in the following aspects: the effective prevention and treatment of shock to reduce the organ damage to ischemia and anoxia, the treatment of inhalation injury to prevent and treat respiratory failure, the strengthened prevention and treatment of infection and immune conditioning to prevent the uncontrolled inflammatory response, the active treatment of burn wounds to prevent and treat wound sepsis, the strengthened support of organ function and nutrition to modulate the hypermetabolism, the strengthened research of basic and translational medicine for precise implementation. The author hopes this paper will be a meaningful reference for readers.

Objective:To investigate the effects and mechanism of mitochondrial transcription factor A (TFAM) and cytochrome c oxidase (COX) pathway in the energy production of hypoxic cardiomyocytes of rats regulated by tumor necrosis factor receptor associated protein 1 (TRAP1).Methods:The cardiomyocytes were isolated from 135 neonatal Sprague-Dawley rats (aged 1-3 d) and cultured for the following experiments. (1) Cells were collected and divided into normoxia blank control (NBC) group, hypoxia blank control (HBC) group, hypoxia+ TRAP1 over-expression control (HTOC) group, and hypoxia+ TRAP1 over-expression (HTO) group according to the random number table (the same grouping method below), with 1 bottle in each group. Cells in NBC group were cultured routinely, cells in HBC group were cultured in hypoxic condition for 6 hours after routine culture, cells in HTOC and HTO groups were respectively added with TRAP1 over-expression empty virus vector and TRAP1 over-expression adenovirus vector virus suspension for transfection for 48 hours after routine culture and then cultured in hypoxic condition for 6 hours. The protein expression of TFAM of cells in each group was detected by Western blotting. (2) Cells were collected and divided into NBC, HBC, HTOC, HTO, HTO+ TFAM interference control (HTOTIC), and HTO+ TFAM interference (HTOTI) groups, with 1 well in each group. Cells in the former 4 groups were dealt with the same methods as the corresponding groups in experiment (1). Cells in HTOTIC and HTOTI groups were respectively added with TFAM interference empty virus vector and TFAM interference adenovirus vector virus suspension for transfection for 48 hours, and the other processing methods were the same as those in HTO group. The content of ATP of cells in each group was determined by ATP determination kit and microplate reader, and the COX activity of cells in each group was determined by COX activity assay kit and microplate reader. (3) Cells were collected and divided into NBC group, normoxia+ sodium azide (NSA) group, HBC group, and hypoxia+ sodium azide (HSA) group, with 1 well in each group. Cells in NBC and HBC groups were respectively dealt with the same methods as the corresponding groups in experiment (1). Cells in NSA and HSA groups were respectively added with 32 nmol sodium azide at 30 min before experiment or hypoxia, and then cells in HSA group were cultured in hypoxic condition for 6 hours. The content of ATP was determined by the same method as above. The above three experiments were repeated for three times. Data were statistically analyzed with one-way analysis of variance and least significant difference test.Results:(1) Compared with that in NBC group, the protein expression of TFAM of cells in HBC group was significantly decreased ( P<0.01). Compared with that in HBC group or HTOC group, the protein expression of TFAM of cells in HTO group was significantly increased ( P<0.01). (2) Compared with 0.552±0.041 and 1.99±0.15 in NBC group, the COX activity (0.270±0.044) and ATP content (1.09±0.11) of cells in HBC group were significantly decreased ( P<0.01). Compared with 0.269±0.042 and 1.17±0.12 in HBC group and those in HTOC group, the COX activity (0.412±0.032 and 0.404±0.016) and ATP content (1.75±0.06 and 1.69±0.07) of cells in HTO and HTOTIC groups were significantly increased ( P<0.01). Compared with those in HTO and HTOTIC groups, the COX activity (0.261±0.036) and ATP content (1.23±0.07) of cells in HTOTI group were significantly decreased ( P<0.01). (3) Compared with that in NBC group, the ATP content of cells in NSA and NBC groups was significantly decreased ( P<0.01). Compared with that in HBC group, the ATP content of cells in HSA group was significantly decreased ( P<0.01). Conclusions:TRAP1 can increase the COX activity of cardiomyocytes by raising the expression of TFAM, and finally alleviate the impairment in energy production of cardiomyocytes caused by hypoxia.

Electric burn is a kind of severe burn with a high disability rate. Although some experience in the diagnosis and treatment of electric burn has been accumulated over the years, there still lacks consensus on a standard treatment of the electric burn wound. To improve the treatment level and the life quality of electric burn patients, the Burns and Trauma branch of Chinese Geriatrics Society and the Expert Committee of Standardization Construction of Wound Repair Department under Chinese Medical Doctor Association have made the consensus on electric burn wound management and repair according to relevant research reports at home and abroad. In this consensus, the standardized wound repair measures of electric burns are systematically introduced from the aspects of injury mechanism, pathophysiological changes, clinical manifestations and diagnosis of wounds, debridement and repair, and matters needing attention, so as to provide a reference for clinical diagnosis and treatment.

After the notice strengthening the management of diagnosis and treatment of chronic wounds on the body surface is issued by the General Office of the National Health and Health Commission [(2019) No.865], how to speed up the construction of wound repair discipline in China, especially how to build a group of high-level wound repair department, become an important and urgent task for the medical workers who are interested in the construction of wound repair discipline. The authors put forward suggestions on the construction of high-level wound repair department from five elements, including attention from departments and hospitals, talent construction, supporting conditions construction, academic and technological development, and department culture construction. The authors hope that it will be a reference to colleagues who are preparing for the wound repair department in China.