Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCD^SS) and the VCD depression resilient group (VCD^RES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.

Empathy is crucial for communication and survival for individuals. Whether empathy in pain contagion shows sex differences and its underlying mechanisms remain unclear. Here, we report that pain contagion can occur in stranger female rats, but not in stranger males. Blocking oxytocin receptors in the anterior cingulate cortex (ACC) suppressed pain contagion in female strangers, while oxytocin administration induced pain contagion in male strangers. In vitro, corticosterone reduces neuronal activation by oxytocin. During male stranger interactions, higher corticosterone decreased oxytocin receptor-positive neuronal activity in the ACC, suppressing pain contagion. These findings highlight the role of oxytocin in pain contagion and suggest that sex differences in empathy may be determined by the balance of oxytocin and corticosterone in the ACC. This study suggests an approach for the treatment of certain mental disorders associated with abnormal empathy, such as autism and depression.
Animals ; Oxytocin/pharmacology* ; Gyrus Cinguli/drug effects* ; Male ; Female ; Corticosterone/pharmacology* ; Empathy/drug effects* ; Sex Characteristics ; Receptors, Oxytocin/antagonists & inhibitors* ; Pain/psychology* ; Rats ; Rats, Sprague-Dawley ; Neurons/metabolism*

Objective To design and synthesize dual-target antidepressant compounds possessing high-affinity binding to the serotonin 1A receptor(5-HT1A)and dual-site synergistic inhibition of the serotonin transporter(SERT).Methods Based on a dual-target synergistic mechanism,benzodioxolane derivatives were designed via scaffold hopping strategy before being synthesized.Their binding affinities to both targets were determined via competitive radioligand binding assays,and their binding modes were investigated using molecular docking.Results Eleven structurally novel target compounds were synthesized and structurally characterized by electrospray ionization mass spectrometry(ESI-MS)and nuclear magnetic resonance(NMR)spectroscopy.Compound 18b demonstrated dual nanomolar affinity for both the 5-HT1A receptor(Ki=2.72 nmol/L)and SERT(Ki=8.85 nmol/L).Molecular docking revealed that its inhibitory effect on SERT resulted from simultaneous occupation of the orthosteric site S1(Asp98 salt bridge)and the allosteric site S2(Arg104 rr-cation interaction),while its high affinity for 5-HT1A depended on the Asp116332 salt bridge anchor and π-π stacking with Phe362652.Conclusion The benzodioxolane-scaffold compounds designed and synthesized in this study exhibited functional synergy between simultaneous occupation of both the S1 and S2 sites of SERT and high-affinity binding to the 5-HT1Areceptor.Among them,compound 18b demonstrates superior activity and promises to be a lead compound for more investigation.

Objective: To investigate the current status and influencing factors of quality of life among HIV/AIDS cases, so as to provide the basis for improving HIV/AIDS cases quality of life. Methods: From March to July 2024, HIV/AIDS cases under follow-up management at various community health service centers in Jinshan District, Shanghai Municipality, were selected as the survey subjects using a convenience sampling method. Demographic information and receiving antiretroviral therapy (ART) were collected through questionnaire surveys. Quality of life was assessed using the Chinese version of the World Health Organization Quality of Life Questionnaire for HIV brief version. A multiple linear regression model was employed to analyze the factors affecting quality of life. Results: A total of 179 HIV/AIDS cases were investigated, including 150 males (83.80%) and 29 females (16.20%), with a mean age of (47.00±12.90) years. The subjective self-evaluation score for the quality of life among HIV/AIDS cases was (13.87±2.84) points. The scores in the domains of physical, psychological, independence, social relationship, environment, and spiritual support/religion/personal beliefs were (14.77±2.64) (13.57±2.04) (13.86±2.04) (12.99±2.26) (13.58±1.98) (14.59±3.05) points, respectively. Multiple linear regression analysis revealed statistically significant associations (all P<0.05) between the following factors and quality of life domain scores: educational level (college degree or above, β' =0.162) and receiving ART (β' =-0.197) were associated with the subjective self-evaluation domain score; educational level (college degree or above, β' =0.186) and receiving ART (β' =-0.299) were associated with physical domain score; receiving ART (β' =-0.263) and symptoms related to sexually transmitted diseases (β' =-0.243) were associated with psychological domain score; occupation (retirees, β' =-0.191) and symptoms related to sexually transmitted diseases (β' =-0.220) were correlated with the independence domain score; annual household income per capita (≥30 000 yuan, β' =0.281) and receiving ART (β' =-0.299) were correlated with the social relationship domain score; educational level (college degree or above, β' =0.206) and receiving ART (β' =-0.285) were correlated with the environment domain score; and receiving ART (β' =-0.492) and duration since HIV confirmation (3 to <6 years, β' =0.233; ≥6 years, β' =0.161) were correlated with the spiritual support/religion/personal beliefs domain score. Conclusions The overall quality of life among HIV/AIDS cases in Jinshan District is relatively good, but the domains of psychological, independence, and social relationship were still room for improvement. It is mainly influenced by factors such as occupation, educational level, annual household income per capita, receiving ART, symptoms related to sexually transmitted diseases, and duration since HIV confirmation.

Objective To investigate the effect of gender on prognosis after transcatheter patent foramen ovale(PFO)closure in patients with cerebral infarction or transient ischemic attack.Methods A retrospective cohort study was conducted involving patients with cerebral infarction or transient ischemic attack(TIA)who underwent PFO closure at our hospital between January 2013 and December 2023.The patients were grouped by gender,and related data were collected,including age,comorbidities,Risk of Paradoxical Embolism(RoPE)score,laboratory results,findings of transthoracic/transesophageal echocardiography(TTE/TEE),and post-procedural complications,such as device-related thrombosis(DRT),recurrent stroke,bleeding,and atrial fibrillation(AF).Results A total of 112 patients were enrolled,including 59 males and 53 females,at a mean age of 42.47±12.35 years.The females had significantly higher preoperative RoPE score than the males(6.6±1.4 vs 6.0±1.5,P=0.046),and a statistical difference was observed in the distribution of infarction sites between them(Chi-square=10.25,P=0.006),indicating that the males were prone to posterior circulation infarction.Intraoperative transthoracic echocardiography revealed a greater distance from the PFO to the aortic root in the females(9.3±2.4 mm vs 7.6±2.0 mm,P<0.001).During a median follow-up of 4 years,the male group had 1 case of myocardial infarction,1 cerebral hemorrhage,1 paroxysmal AF,2 gingival bleeding episodes,and 1 skin ecchymosis.In the female group,1 case experienced pulmonary embolism,1 paroxysmal atrial fibrillation,3 gingival bleeding episodes,2 skin ecchymoses,2 recurrent cerebral infarctions,and 2 recurrent TIAs.There was no statistical difference in overall adverse events between gender(P=0.291).Although the females had higher rates of recurrent cerebral infarction and TIA,this difference lacked statistical significance(P=0.222).Multivariate Cox regression analysis indicated that after adjusting for various potential confounding factors,such as RoPE score,age,hypertension,coronary heart disease,and other factors,gender was not an independent predictor of composite endpoint events after surgery.Conclusion Gender does not significantly affect overall prognosis after PFO closure in patients with cerebral infarction or TIA.However,females showed a trend toward higher rates of recurrent cerebral infarction and TIA.

Objective:To develop a deep learning-based segmentation model for anterior segment ultrasound biomicroscopy (UBM) images to automatically segment the anterior segment tissues of patients with primary angle-closure glaucoma (PACG).Methods:A single-center retrospective case series was conducted.A small-scale dataset comprised 468 UBM images of the anterior chamber angle closure from 156 patients with PACG who underwent the UBM examination at Tianjin Medical University Eye Hospital between July 12, 2022, and February 20, 2023.The UBM images were randomly split into a training dataset of 228 images and a testing dataset of 152 images using a random seed method in a ratio of 6∶4.The models were trained using the PSPNet model with MobileNet V2 and ResNet50 as backbones, the DeepLab v3+ model with MobileNet V2 and Xception as backbones, and the SegFormer model with MiT-B0 and MiT-B2 as backbones.The testing dataset was used for result prediction and to achieve segmentation of four regions: the cornea and sclera, iris, ciliary body, and anterior lens surface.To evaluate the performance of the models in segmenting the anterior segment structures, multiple metrics were assessed, including the mean intersection over union (mIoU), Dice coefficient, precision, recall, false negative rate, and specificity.A comparative analysis of the test results across the different models was subsequently performed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2023KY-05).Results:The two models with the best segmentation performance were PSPNet and DeepLab v3+ .The PSPNet model with ResNet50 as the backbone achieved the mIoU of 85.11%, Dice coefficient of 91.38%, precision of 91.83%, recall of 90.94%, false negative rate of 9.06%, and specificity of 98.89%.The DeepLab v3+ model with MobileNet V2 as the backbone achieved an mIoU of 85.84%, Dice coefficient of 92.01%, precision of 92.67%, recall of 91.36%, false negative rate of 8.64%, and specificity of 98.90%.Among the five key metrics, mIoU, Dice coefficient, recall, false negative rate, and specificity, DeepLab v3+ exhibited the best segmentation performance.In addition, the DeepLab v3+ model with Xception as the backbone had the highest precision among all models, reaching 92.77%.Conclusions:The deep learning-based DeepLab v3+ model achieves precise segmentation of anterior segment tissue structures in PACG anterior segment UBM image segmentation, providing auxiliary support for clinical diagnosis.

Objective:To explore a new surgical approach [anteromedial approach of the hip (AMA)] for Pipkin Ⅰ and Ⅱ femoral head fractures through an imaging and anatomical study.Methods:The hip imaging data were collected of the 38 patients who had undergone lower limb CT angiography for open tibiofibular fractures at Department of Orthopaedics, The Sixth People’s Hospital, School of Medicine, Shanghai Jiao Tong University from June 2023 to January 2024. There were 20 males aged (40.9±3.5) years and 18 females aged (41.5±3.3) years. The origins and shapes of the femoral artery and its main branches were observed. The distances between the femoral head and the femoral artery, the medial femoral circumflex artery, and the lateral femoral circumflex artery were measured. Four fresh adult cadavers were collected, including 2 males and 2 females. Their ages of death were 56, 65, 72 and 78 years old, respectively. An incision was made along the axis of the limb at the midpoint of the inguinal ligament at the 4 fresh cadavers. After the femoral head was exposed through the gap between the femoral artery and the femoral nerve, the range of the femoral head exposed was marked.Results:The femoral artery ran along the anteromedial side of the femoral head. The shortest distance between the medial femoral circumflex artery and the femoral head was (13.1±5.7) mm, and the shortest distance between the origin of the lateral femoral circumflex artery and the femoral head (21.6±8.6) mm. On the lateral view of CT angiography, the distance between the femoral artery and the femoral head was (20.6±4.9) mm at the level of the apex of greater trochanter. Gross observation on the cadavers found only small branches of vessels between the femoral artery and the femoral nerve. After the femoral artery and femoral nerve were respectively pulled medially and laterally, the anterior-inferior part of the femoral head was exposed directly by pulling the muscles to open the joint capsule. The exposure range of the femoral head was further expanded through internal and external rotation of the hip joint under traction. The anatomical gap between the femoral artery and the femoral nerve was named the AMA.Conclusion:AMA utilizes the potential gap between the femoral artery and the femoral nerve, providing a new surgical approach for exposure and fixation of Pipkin type Ⅰ and Ⅱ femoral head fractures.

The free inferior epigastric artery perforator flap is currently a highly regarded autologous breast reconstruction technique. However, in clinical practice, the anatomical characteristics of the lower abdominal vasculature and surrounding tissue structures do not always permit ideal perforator flap harvesting. In many cases, it becomes necessary to preserve a larger rectus abdominis muscle cuff to ensure reliable blood supply to the flap through the perforating vessels. Compared with various forms of rectus abdominis myocutaneous flaps that all require incision of the anterior sheath and intramuscular vascular pedicle dissection, the superficial inferior epigastric artery (SIEA) perforator flap significantly reduces donor-site morbidity. Nevertheless, the anatomical variability of the superficial inferior epigastric vessels increases surgical uncertainty. Based on clinical observations, this study establishes a comprehensive clinical strategy algorithm. Primarily focusing on different configurations of free rectus abdominis flaps, it incorporates additional preparation of free SIEA perforator flaps when anatomical conditions permit. The objectives are to ensure reliable perfusion of the lower abdominal flap while minimizing donor-site damage and reducing surgical complexity.

Objective:To evaluate the efficacy and safety of remedial pedicled rectus abdominis myocutaneous flap transplantation for breast reconstruction.Methods:This retrospective study included 23 female breast cancer patients who underwent autologous breast reconstruction with a remedial pedicled rectus abdominis myocutaneous flap at Hunan Cancer Hospital from June 2022 to June 2023. The patients' ages ranged from 24 to 56 years, with a mean age of (43.2±1.3) years. All patients had previously undergone mastectomy and tumor resection before receiving the remedial pedicled rectus abdominis myocutaneous flap reconstruction. Follow-up was conducted through outpatient visits and telephone interviews, with a median follow-up period of 10 (6-15) months. Observation indicators included survival rate of flaps, patient satisfaction rate and aesthetic outcomes. Adverse reactions including but not limited to flap contracture and deformation, during and following the surgical procedure were also recorded.Results:The remedial pedicled rectus abdominis myocutaneous flap technique was utilized for autologous breast reconstruction in 23 patients. Specifically, this approach was chosen due to two primary reasons: the perforator distance from the vascular pedicle being excessively long in 18 cases, and suboptimal characteristics of the main pedicle in 5 cases. Two types of flap configurations were employed. For 15 patients, a unilateral remedial pedicled rectus abdominis myocutaneous flap was used, with an average flap size of (21.5±0.8) cm in length and (11.2±1.3) cm in width. All flaps demonstrated adequate blood supply without the need for additional vascular anastomosis. For the remaining 8 patients, a combination of a unilateral remedial pedicled rectus abdominis myocutaneous flap and a contralateral free lower abdominal flap was utilized, resulting in an average flap size of (29.3±0.7) cm in length and (12.0±1.8) cm in width. In these cases, the inferior epigastric vessels of the free lower abdominal flap were successfully anastomosed to the internal thoracic vessels of the recipient site, ensuring all flaps survived postoperatively. The survival rate of flaps in 23 patients was 100% (23/23), and the patient satisfaction rate was 100% (23/23). Postoperative evaluation revealed that the reconstructed breasts exhibited satisfactory shape and texture, with no instances of flap contracture or deformation. The reconstructed breasts were largely symmetrical with the contralateral side, leaving only linear scars at the donor and recipient sites. Importantly, there was no significant impact on abdominal wall function, and no adverse reactions such as flap contracture or impaired abdominal wall function were observed in any of the patients.Conclusion:When the characteristics of the perforating vessels in the lower abdomen are suboptimal, the use of a remedial pedicled rectus abdominis myocutaneous flap technique for breast reconstruction can ensure satisfactory outcomes and significantly enhance surgical safety.