In different stages of schizophrenia (SZ), alterations in gray matter volume (GMV) of patients are normally regulated by various pathological mechanisms. Instead of analyzing stage-specific changes, this study employed a multivariate structural covariance model and sliding-window approach to investigate the illness duration-related developmental trajectory of GMV in SZ. The trajectory is defined as a sequence of brain regions activated by illness duration, represented as a sparsely directed matrix. By applying this approach to structural magnetic resonance imaging data from 145 patients with SZ, we observed a continuous developmental trajectory of GMV from cortical to subcortical regions, with an average change occurring every 0.208 years, covering a time window of 20.176 years. The starting points were widely distributed across all networks, except for the ventral attention network. These findings provide insights into the neuropathological mechanism of SZ with a neuroprogressive model and facilitate the development of process for aided diagnosis and intervention with the starting points.
Humans ; Schizophrenia/pathology* ; Gray Matter/pathology* ; Magnetic Resonance Imaging ; Disease Progression ; Male ; Female ; Brain/pathology* ; Cerebral Cortex/pathology* ; Adult

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.

Humans ; Consanguinity ; Exome Sequencing ; Mutation/genetics* ; Sequence Analysis, DNA ; Ciliary Motility Disorders ; Axonemal Dyneins/genetics*

BACKGROUND:Blood flow restriction training has broad application prospects in improving limb muscle strength.It has ideal effects on the upper limbs is ideal,and the specific application scheme has high research value. OBJECTIVE:To explain the influence of blood flow restriction training on the fitness benefits of upper limb muscles and summarize the specific programs of blood flow restriction training for upper limb,attempting to give suggestions on application programs based on existing studies. METHODS:Literature on the application of upper limb blood flow restriction training were searched in CNKI,WanFang,VIP,CBM,PubMed,Embase,EBSCO,Cochrane Library and Web of Science databases.The search terms were"blood flow restriction,blood flow restriction training,pressure training,upper limb,upper arm,forearm,arm,forearm"in Chinese and"blood flow restriction training,blood flow restriction exercise,blood flow restriction therapy,BFR therapy,occlusion training,KAATSU training,BFRT,upper extremity,upper limb,arm,forearm"in English.The relevant articles on the application of blood flow restriction training in the upper limbs included in the database from database inception to December 2022 were selected and screened according to inclusion criteria and exclusion criteria. RESULTS AND CONCLUSION:Firstly,blood flow restriction training is mainly applied to healthy people,special athletes and people with upper limb injury.Secondly,the influence of blood flow restriction training on upper limb muscle fitness is mainly reflected in the increase of upper limb circumference,muscle strength,muscle endurance,muscle thickness,muscle cross-sectional area and explosive power of upper limb,followed by the cross migration phenomenon of the upper limbs.Thirdly,blood flow restriction training for the upper limbs mainly uses inflatable blood flow restriction devices:the cuff width was 3-5 cm,the pressure position was 1/3 of the upper arm,the limiting pressure was 40%-60%arterial occlusion pressure or 80-160 mmHg,the training load is 20%-30%1RM,the training volume is four sessions(30-15-15-15 times),the interval time was 30-60 seconds,and the training frequency was 2 or 3 times per week.

Objective To explore the effect of 2-aminoethoxy-diphenyl borate(2-APB)on H2O2-induced chondro-cyte apoptosis and its mechanism.Methods The experiment was divided into control group,H2O2 group,2-APB group and H2O2+2-APB group.CCK-8 method was used to detect the cell viability of each group;The effect of 2-APB on the morphological changes of chondrocytes induced by H2O2 was observed under microscopy;TUNEL meth-od and flow cytometry were used to detect chondrocyte apoptosis;Flow cytometry was used to detect Lipid reactive oxygen species(ROS);Western blot was used to detect the protein expressions of Cleaved-PARP,p-PKCα and HIF-1α in H2O2-induced cells by 2-APB;Immunofluorescence was used to detect the fluorescent expression of HIF-1α in cells induced by H2O2 by PKCα inhibitor BIM-1.Results 2-APB inhibited H2O2-induced apoptosis in chon-drocytes,and the inhibitory effect was the most significant when the concentration of 2-APB was 100 pmol/L(F=235.80,P＜0.01);22-APB could inhibit the positive rate of H2O2-induced apoptosis of chondrocytes(F=114.80,P＜0.01)and the level of ROS(F=52.99,P＜0.01).and inhibited the expression of Cleaved-PARP(F=10.10,P＜0.05),p-PKCα(F=24.56,P＜0.05)and HIF-1α proteins(F=6.85,P＜0.05).The PKCα in-hibitor BIM-Ⅰ could inhibit the increase in HIF-1α fluorescence intensity caused by H2O2.Conclusion 2-APB can inhibit chondrocytes apoptosis induced by H2O2 through the PKCα/HIF-1α pathway and thus protect chondro-cytes.

Objective:To explore the short-term efficacy on 3D printing assisted reconstruction of traumatic digit joint defects using rib and costo-osteochondral autograft.Methods:From August 2022 to July 2023, 7 patients with open digit joint defects had undergone emergency primary debridement and fracture fixation in the Department of Orthopaedics, 988th Hospital of the Joint Logistics Support Force of PLA. Patients with more phalangeal defects that could not be aligned were treated with antibiotic bone cement filling in the emergency surgery. In the second stage surgery, bone cement was removed and transfer of rib cartilage graft was performed to reconstruct the digit joint defect. According to a 1∶1 3D printed hand templates, rib cartilage grafts were crafted to the shape of digit joints, and then spliced together the digit joints and bone defects for fixation. Follow-up X-ray examinations were taken and assessment of the healing status of rib and fractures of phalangeal and metacarpophalangeal bones were carried out according to the Paley fracture healing score. At the outpatient follow-up, assessment of transferred joint movement and evaluation of upper limb function were conducted according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association. Visual Analogue Scale (VAS) pain scores were evaluated from the affected digits and donor sites.Results:After reconstructive surgery, all 7 patients had primary healing of the wounds of hand. One patient had fat liquefaction at the donor site, and the rest had primary donor site healing. One patient received further surgery for extensor tendon repair after rib cartilage grafting due to the digital extensor tendon injury. All 7 patients were included in postoperative follow-up for 6-11 months, with an average of 9 months. All patients had excellent fracture healing according to the Paley fracture healing score. At the final follow-up, the extension and flexion of the digit joints were found at 40°-80° (average 56.2°) for proximal interphalangeal joints (4 patients), and 10° in extension and 85° in flexion for metacarpophalangeal joint (1 patient). The range of motion of the thumb interphalangeal joint (2 patients) was 20°-35° (average 27.5°). Hand function was assessed according to Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association and it was found that 3 patients were in excellent, 3 in good and 1 in fair.Conclusion:This study focused on the treatment of traumatic digit joint defects by transfer of individually crafted rib cartilages in reconstruction of the defected digit joint. It significantly improves the appearance and function of the defected digit joints, especially suitable for the irregular defects of phalangeal bones.

Cardiovascular dysfunction and reduced exercise capacity are common adverse effects of anti-cancer treatments, severely impacting the prognosis and quality of life of cancer patients. This review summarizes the intervention protocols and application effects of resistance training on cardiovascular function and/or exercise capacity in cancer patients. The aim is to provide a reference for the practice of exercise interventions targeting cardiovascular function and exercise capacity among cancer patients in China.

Objective To compare the perioperative efficacy and safety of da Vinci robot-assisted thoracoscopic surgery (RATS) for treatment of anterior mediastinal tumors through subxiphoid versus lateral thoracic approaches under the laryngeal mask anesthesia. Methods We retrospectively analyzed the clinical data of 102 patients with anterior-mediastinal tumors treated by RATS under laryngeal mask anesthesia completed by the same operator. Forty-five patients underwent the subxiphoid approach (subxiphoid group), and 57 patients were treated with the lateral thoracic approach (lateral thoracic group). The operating time, intraoperative bleeding, and total postoperative drainage volume in the two groups were compared and analyzed. Results All patients successfully completed resection of the anterior mediastinal tumor without the occurrence of perioperative death. In terms of total postoperative drainage volume, postoperative drainage time, postoperative hospital stay, and VAS pain on postoperative days 2 and 3, the subxiphoid group was more advantages (P < 0.05). No statistically significant difference was found between the two groups in terms of operative time, docking time, total operative time, intraoperative bleeding volume, postoperative day 1 VAS pain score, or postoperative complications (P > 0.05). Conclusion The subxiphoid approach of RATS is safe and feasible for resection of anterior mediastinal tumors. Compared with the lateral thoracic approach, the subxiphoid approach has advantages in terms of rapid postoperative recovery and postoperative pain.

OBJECTIVE: To investigate whether gut microbiota disturbance after cardiopulmonary bypass (CPB) contributes to the development of perioperative neurocognitive disorders (PND). METHODS: Fecal samples were collected from healthy individuals and patients with PND after CPB to prepare suspensions of fecal bacteria, which were transplanted into the colorectum of two groups of pseudo-germ-free adult male SD rats (group NP and group P, respectively), with the rats without transplantation as the control group (n=10). The feces of the rats were collected for macrogenomic sequencing analysis, and serum levels of IL-1β, IL-6 and TNF-α were measured with ELISA. The expression levels of GFAP and p-Tau protein in the hippocampus of the rats were detected using Western blotting, and the cognitive function changes of the rats were assessed with Morris water maze test. RESULTS: In all the 3 groups, macrogenomic sequencing analysis showed clustering and clear partitions of the gut microbiota after the transplantation. The relative abundances of Klebsiella in the control group (P < 0.005), Akkermansia in group P (P < 0.005) and Bacteroides in group NP (P < 0.005) were significantly increased after the transplantation. Compared with those in the control group, the rats in group NP and group P showed significantly decreased serum levels of IL-1β, IL-6 and TNF-α and lowered expression levels of GFAP and p-Tau proteins (all P < 0.05). Escape platform crossings and swimming duration in the interest quadrant increased significantly in group NP (P < 0.05), but the increase was not statistically significant in group N. Compared with those in group P, the rats in group NP had significantly lower serum levels of IL-1β, IL-6 and TNF-α and protein expressions of GFAP and p-Tau (all P < 0.05) with better performance in water maze test (P < 0.05). CONCLUSION In patients receiving CPB, disturbances in gut mirobiota contributes to the development of PND possibly in relation with inflammatory response.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Cardiopulmonary Bypass ; Gastrointestinal Microbiome ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Neurocognitive Disorders