BACKGROUND: Telesurgery has the potential to overcome spatial limitations for surgeons, which depends on surgical robot and the quality of network communication. However, the influence of network latency and bandwidth on telesurgery is not well understood. METHODS: A telesurgery system capable of dynamically adjusting image compression ratios in response to bandwidth changes was established between Beijing and Sanya (Hainan province), covering a distance of 3000 km. In total, 108 animal operations, including 12 surgical procedures, were performed. Total latency ranging from 170 ms to 320 ms and bandwidth from 15-20 Mbps to less than 1 Mbps were explored using designed surgical tasks and hemostasis models for renal vein and internal iliac artery rupture bleeding. Network latency, jitter, frame loss, and bit rate code were systemically measured during these operations. National Aeronautics and Space Administration Task Load Index (NASA-TLX) and a self-designed scale measured the workload and subjective perception of surgeons. RESULTS: All 108 animal telesurgeries, conducted from January 2023 to June 2023, were performed effectively over a total duration of 3866 min. The operations were completed with latency up to 320 ms and bandwidths as low as 1-5 Mbps. Hemostasis for vein and artery rupture bleeding models was effectively achieved under these low bandwidth conditions. The NASA-TLX results indicated that latency significantly impacted surgical performance more than bandwidth and image clarity reductions. CONCLUSIONS This telesurgery system demonstrated safety and reliability. A total of 320 ms latency is acceptable for telesurgery operations. Reducing image clarity can effectively mitigate the potential latency increase caused by decreased bandwidth, offering a new method to reduce the impact of latency on telesurgery.
Animals ; Robotic Surgical Procedures/methods* ; Laparoscopy/methods*

Coronavirus disease 2019 (COVID-19) is a multi-system disease that can lead to various severe complications. Acute limb ischemia (ALI) has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis. However, the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood. Hypercoagulability and thrombosis are considered important mechanisms, but we also emphasize the roles of vasospasm, hypoxia, and acidosis in the pathogenesis of the disease. The angiotensin-converting enzyme 2 (ACE2) pathway, inflammation, and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19. Furthermore, we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic, age, and gender perspectives based on our analysis of molecular mechanisms. Additionally, we summarize therapeutic approaches such as use of the interleukin-6 (IL-6) blocker tocilizumab, calcium channel blockers, and angiotensin-converting enzyme inhibitors, providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
Humans ; COVID-19/physiopathology* ; Ischemia/etiology* ; SARS-CoV-2 ; Extremities/blood supply* ; Risk Factors ; Interleukin-6/antagonists & inhibitors* ; Acute Disease ; Angiotensin-Converting Enzyme 2

Objective:To discuss the differential expression of microRNA(miR)-125a-5p in peripheral blood mononuclear cells(PBMCs)of the patients with mycobacterium tuberculosis(MTB)infection and its effect on macrophage polarization,and to clarify its clinical significance.Methods:A total of 40 patients with active tuberculosis(ATB)(ATB group),35 patients with latent tuberculosis infection(LTBI)(LTBI group),and 40 healthy physical examinees(control group)clinically diagnosed from July 2022 to June 2023 were selected.The fasting blood samples of the subjects in three groups were collected next morning after 12 h of fasting,and then serum was separated.Enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of inflammatory factors in the serum of the subjects in various groups.Simultaneously,the PBMCs were extracted from the subjects in various groups;flow cytometry was used to detect the expression levels of CD80 and CD206 proteins in the PBMCs of the subjects in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of microRNA(miR)-125a-5p and interleukin-6(IL-6)mRNA in PBMCs of the subjects in various groups.Results:There were no statistically significant differences in the general information of the subjects among three groups(P>0.05).Compared with control group,the erythrocyte sedimentation rate(ESR),percentages of monocytes(MONO),tumor necrosis factor-α(TNF-α)levels,and interleukin-10(IL-10)levels in serum of the patients in ATB group and LTBI group were significantly increased(P<0.05),and the percentages of lymphocytes(LY)were significantly decreased(P<0.05);compared with ATB group,the ESR and level of IL-10 in serum of the patients in LTBI group were significantly decreased(P<0.05),and the percentage of LY was significantly increased(P<0.05);there were statistically significant differences in the counts of white blood cell(WBC)of the subjects among various groups(P>0.05).The flow cytometry results showed that compared with control group,the expression levels of CD80 and CD206 proteins in PBMCs of the patients in ATB group and LTBI group were significantly increased(P<0.05).Compared with ATB group,the expression level of CD206 protein in the PBMCs of the patients in LTBI group was significantly increased(P<0.05),and the expression level of CD80 protein was significantly decreased(P<0.05).The RT-qPCR results showed that compared with control group,the expression levels of miR-125a-5p and IL-6 mRNA in the PBMCs of the patients in ATB group and LTBI group were significantly increased(P<0.05);compared with ATB group,the expression levels of miR-125a-5p and IL-6 mRNA in PBMCs of the patients in LTBI group were significantly increased(P<0.05).The correlation analysis results showed that the miR-125a-5p expression level was positively correlated with the TNF-α level and IL-6 mRNA expression level(r=0.406,P<0.05;r=0.351,P<0.05),and negatively correlated with the IL-10 level(r=-0.368,P<0.05).The area under the receiver operating characteristic(ROC)curve(AUC)value of miR-125a-5p expression level for diagnosing LTBI patients was 0.89(P<0.01),with a sensitivity of 0.85 and a specificity of 0.88.Conclusion:The expression level of miR-125a-5p in PBMCs of the patients in LTBI group is significantly increased,and it can affect the macrophage polarization to M1,promote the inflammatory response process of macrophages and participate in the occurrence and development of pulmonary tuberculosis.

Objective To explore the characteristics and influencing factors of family resilience among Chinese PLA Army personnel.Methods A total of 8 094 military personnel subjected with cluster sampling were surveyed with family resilience scale(FRS)and self-designed questionnaire for basic information on military families.Independent sample t test,one-way analysis of variance and step-up regression analysis were employed to analyze the family resilience.Results ① The results of demographic variable analysis showed that there were significant differences in family resilience among the personnel with different marital status,from one-child family or not,birth in rural/urban areas,personnel category,age and education level(P＜0.05).② Family factors analysis indicated that different family structure,different family relationships,family rearing styles,recent separation from family members,and frequency of contacting family members had certain effects on family resilience(P＜0.05).③ When family relationship,family rearing styles,frequency of contacting family members,birth place,recent separation from family,personnel category,from one-child family,and education level entered the regression equation,the resilience level of army personnel'families was increased by 8.197 for every 1 unit increase in family relationship,and the level of family resilience was increased by 4.688 for every 1 unit increase in family contact frequency(F=202.168,P＜0.05).Conclusion The overall level of family resilience of army personnel is good.The risk factors for family resilience are recent separation from their families for ≥1 year,officers,not from only-children family,and the protective factors are harmonious relationship with their families,democratic family rearing style,contacting with their families weekly,urban birth,and bachelor degree or above.

ObjectiveTo classify subtypes among middle-aged and elderly type 2 diabetes mellitus (T2DM) patients aged between 35‒74 years in Shanghai suburbs, to compare their characteristics and analyze incidence risk for cerebrovascular disease among these subtypes, so as to promote personalized and precise treatment of T2DM. MethodsA total of 7 792 patients with T2DM who completed a baseline survey from 2016 and 2019 were selected as the research subjects, based on the data from a natural population cohort and biobank in Shanghai suburbs. Patients were stratified by gender and clustered into subtypes using k-means method based on baseline parameters including the age at T2DM diagnosis, body mass index (BMI), fasting blood glucose, and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Patients were followed up until March 31, 2023. Multivariate Cox regression models were used to analyze the association between subtypes and incidence risk for cerebrovascular disease, and those with cerebrovascular disease within 1 year of follow-up survey were excluded from sensitivity analysis. ResultsAmong the 7 792 patients with T2DM, 3 615 were males and 4 177 were females. Stratified by gender, 4 subgroups were identified through k-means clustering analysis, namely poor blood glucose control subgroup, severe insulin-resistant subgroup, younger onset subgroup, and older onset subgroup. The median follow-up time was 4.30 years, during which 1 960 cerebrovascular disease events were observed (844 in males, 1 116 in females). After adjusting for smoking, alcohol consumption, weekly exercise, family history of diabetes mellitus, and duration of diabetes mellitus, among male patients, the incidence risk for cerebrovascular disease was lower in the younger onset subgroup (HR=0.59, 95%CI: 0.48‒0.73, P<0.001), poor blood glucose control subgroup (HR=0.81, 95%CI: 0.65‒1.00, P=0.046), and severe insulin-resistant subgroup (HR=0.61, 95%CI: 0.50‒0.75, P<0.001), compared to the older onset subgroup. While among female patients, the incidence risk for cerebrovascular disease was also lower in the younger onset subgroup (HR=0.68, 95%CI: 0.57‒0.80, P<0.001), poor blood glucose control subgroup (HR=0.73, 95%CI: 0.60‒0.89, P=0.002), and severe insulin-resistant subgroup (HR=0.72, 95%CI: 0.61‒0.85, P<0.001), compared to the older onset subgroup. Results of the sensitivity analysis were consistent with the main findings. ConclusionAmong middle-aged and elderly T2DM patients in suburban Shanghai, both male and female patients have the highest incidence risk for cerebrovascular disease in the older onset subgroup. Subtyping of T2DM patients can help to identify the high-risk populations of cerebrovascular disease.

ObjectiveTo observe the effect of modified Dahuang Huanglian Xiexintang on mitochondrial autophagy and browning of visceral adipose tissue in obese type 2 diabetes mellitus （T2DM） model ZDF rats. MethodForty ZDF rats were induced with a high-fat diet to establish an obese T2DM model. The rats were randomly divided into five groups： Model group， metformin group （0.18 g·kg^-1）， and high， medium， and low dose groups of modified Dahuang Huanglian Xiexintang （2.16， 1.08， 0.54 g·kg^-1）， with eight rats in each group. Additionally， eight ZDF （fa/+） rats were assigned to the normal group. All groups received an intragastric volume of 10 mL·kg^-1， with the model and normal groups receiving the same volume of purified water once daily for 12 weeks. Fasting blood glucose （FBG） was regularly measured. After 12 weeks of intervention， the body weight， epididymal fat weight， and serum levels of glucose （GLU）， glycated serum protein （GSP）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in epididymal fat tissue. Transmission electron microscopy （TEM） was employed to observe mitochondrial autophagy in adipocytes. Real-time PCR was used to detect the mRNA expression of hypoxia-inducible factor-1α （HIF-1α）， Bcl-2/adenovirus E1B 19 kDa interacting protein 3 （BNIP3）， microtubule-associated protein 1 light chain 3B （LC3B）， p62/SQSTM1， uncoupling protein 1 （UCP1）， iodothyronine deiodinase 2 （Dio2）， and PR domain containing 16 （Prdm16） in epididymal fat. Western blot was used to detect the protein expression of HIF-1α， BNIP3， LC3B， p62， and UCP1 in epididymal fat. ResultCompared with the normal group， the model group showed pathological changes in epididymal fat， with adipocyte mitochondrial condensation and numerous autophagosomes indicating mitochondrial autophagy. The model group also exhibited significantly increased body weight， epididymal fat weight， FBG， GLU， GSP， TC， TG， and LDL-C levels （P<0.01）， significantly decreased HDL-C levels （P<0.01）， significantly elevated mRNA and protein expression of HIF-1α， BNIP3， and LC3B （P<0.01）， significantly reduced mRNA and protein expression of p62 and UCP1 （P<0.01）， and significantly reduced mRNA expression of Dio2 and Prdm16 （P<0.01）. Compared with the model group， all intervention groups showed varying degrees of improvement in epididymal fat pathology. The metformin group and high-dose modified Dahuang Huanglian Xiexintang group displayed intact mitochondrial morphology， clear cristae， uniform matrix， and few autophagosomes and autophagosomes in the adipocyte cytoplasm. The metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced body weight and epididymal fat weight （P<0.01）. The epididymal fat index was reduced in all intervention groups （P<0.05）， and FBG was lowered in all intervention groups （P<0.01）.Serum GSP， GLU， TG， and LDL-C levels were reduced in the metformin group and the high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The serum TC level was significantly reduced in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.01）， and HDL-C levels were significantly increased in all intervention groups （P<0.05， P<0.01）. The mRNA and protein expression of HIF-1α， BNIP3， and LC3B were significantly reduced， and UCP1 protein expression was significantly increased in the metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The mRNA and protein expression of p62， Dio2， and Prdm16 were significantly increased in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. ConclusionModified Dahuang Huanglian Xiexintang may inhibit mitochondrial autophagy and promote the browning of visceral adipose tissue through the HIF-1α/BNIP3/LC3B pathway， thereby improving glucose and lipid metabolism in obese T2DM rats.

Background::Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods::Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR. Results::Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter –42 bp to –28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression. Conclusions::This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

The development process of non-invasive ventilation (NIV) has been nearly a century, reflecting the history of modern medical development. At present, NIV is widely used in pediatrics,and which is an important component of respiratory support therapy, as well as an important method for treating acute respiratory failure in children. However, non-invasive ventilation, due to its own characteristics, has limitations and contraindications, and cannot replace invasive mechanical ventilation. Before using NIV, it is necessary to carefully evaluate the patient's condition. NIV may fail in the treatment of pediatric patients with acute respiratory distress syndrome, immune dysfunction and post-extubation with acute respiratory failure, leading to poor prognosis. When the efficacy of NIV is poor and the condition worsens, prompt tracheal intubation and invasive mechanical ventilation treatment should be performed. Medical personnel should strengthen their training on the use of NIV.Teams with experienced members and refined management are important guarantees for the safe and effective use of NIV.

Kidney organoids are induced and differentiated from human pluripotent stem cells(PSCs)or adult stem cells(ASCs)derived from tissue sources,primarily composed of nephron struc-tures.However,due to the absence of a supporting vascular network,kidney organoids often exhibit immature tissue structures and limited growth.Therefore,vascularization in kidney organoids remains a pressing challenge in this field.Currently,the methods such as transplantation into immunodeficient animals,alterations in induced differentiation protocols,utilization of microfluidic chips,and manipula-tion of extracellular matrix and oxygen concentrations may facilitate vascularization of kidney organoids,which provides a new perspective for the scientific study and clinical application of kidney organoids.

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.