ObjectiveThis study aimed to investigate the therapaeutic effects of rabies virus glycoprotein （RVG）-modified mesenchymal stem cell-derived exosomes （MSC-EXO） in a mouse model of obsessive-compulsive disorder （OCD）， and to explore the underlying mechanisms. MethodsPrimary mouse adipose-derived MSCs were isolated and characterized by adipogenic and osteogenic differentiation assays and flow cytometry. RVG-overexpressing MSCs were generated， and the derived exosomes were characterized by nanoparticle size analysis， Western blotting， and transmission electron microscopy. An OCD mouse model was established using quinpirole， and the mice were divided into five groups： control， model， clomipramine（CMI）， MSC-EXO， and RVG-MSC-EXO. Compulsive-like behaviors and cognitive function were evaluated using the compulsive checking test， open field test， marble-burying tes， and Morris water maze. The levels of inflammatory cytokines in the mouse prefrontal cortex were measured by qPCR and ELISA. Microglial polarization in the prefrontal cortex was assessed by immunofluorescence staining. The brain-targeting ability of RVG-MSC-EXO was verified using an in vivo imaging system （IVIS）. ResultsRVG-modified MSC-derived exosomes exhibited significant brain-targeting ability in mice. Exosome treatment significantly reduced compulsive checking and marble-burying behaviors in mice. Exosome treatment decreased pro-inflammatory cytokines and increased anti-inflammatory cytokines. Exosome treatment promoted a shift in microglial polarization from the M1 phenotype to M2 phenotype. ConclusionRVG-modified mesenchymal stem cell-derived exosomes can target the mouse brain， alleviate neuroinflammation by promoting microglial polarization towards the M2 phenotype， and ultimately reduce compulsive-like behaviors in OCD mice.

ObjectiveTo explore whether fluoroethylnormemantine （FENM）， an NMDA receptor antagonist， could improve compulsive-like behaviors and to investigate its underlying mechanisms in the RU24969-induced obsessive-compulsive disorder （OCD） mouse model. MethodsThirty-two mice were randomly assigned to four groups： Saline （n=8）， RU24969 （n=8）， RU+FENM （n=8）， and FENM （n=8）. Mice received FENM or an equivalent volume of saline for pre-treatment， followed by RU24969 or saline for model induction 30 minutes later. Behavioral tests were performed 1 hour after modeling， and serum samples were collected to measure the level of brain-derived neurotrophic factor （BDNF）. Evans Blue dye was intravenously injected to assess dye content in brain tissue， thereby evaluating potential blood-brain barrier damage. ResultsFENM treatment significantly improved repetitive stereotyped circling behavior （F=39.850， P＜0.001） and alleviated persistent motor activity （F=50.200， P＜0.001） in RU24969 model mice. Additionally， FENM treatment significantly increased serum BDNF level in RU24969-induced OCD mice （F=18.930， P＜0.001）. ConclusionsFENM ， an NMDA receptor antagonist， may alleviate compulsive behaviors in OCD mice by modulating BDNF levels ， thereby exerting anti-compulsive effects. Neither the RU24969 model nor FENM treatment significantly affectes blood-brain barrier integrity.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective:To study the feasibility of design and harvest of free medial sural artery perforator flap with the "two-point and two-line method".Methods:From September 2022 to June 2023, Suzhou Ruihua Orthopaedic Hospital implemented the "two-point and two-line method" to guide preoperative perforator positioning and flap design. Thirty medial sural artery perforator flaps were successfully harvested with the method, and 21 wounds of hand and 9 of foot and ankle were reconstructed with the flaps. The size of soft tissue defects were 2.5 cm×2.5 cm-7.0 cm×14.5 cm, and the flaps size were 3.0 cm×3.0 cm-7.5 cm×15.0 cm. All donor sites were directly closed or by skin grafting. All patients were entered in 6-15 months of postoperative outpatient follow-up, and the recovery of donor and recipient sites was assessed by the comprehensive evaluation scales. The sensory function of the flaps was evaluated using the sensory function evaluation standard of British Medical Research Council (BMRC).Results:All perforators were successfully located with 47 perforators in total, and all of them were musculocutaneous perforator. It was found that there was 1 perforator in 14 flaps, 2 perforators in 15 flaps and 3 perforators in 1 flap. All 30 flaps survived after surgery, beside 2 flaps that had arterial insufficiency but survived successfully after surgical exploration. All donor sites healed in one stage. Comprehensive evaluation scale of flap was employed to evaluate the flaps and the scores were 84 points to 96 points with an average score of 92.5 points. The excellent and good grades were achieved in 27 flaps and 3 flaps, respectively, with a combined excellent and good rate at 100%. Sensation of the flaps was evaluated by BMRC with 1 flap of S 1, 17 of S 2 and 12 of S 3. Conclusion:The "two-point and two-line method" has been used in design of the perforator flap of medial sural artery. This method is simple and accurate, and is feasible and ideal in design of flaps before surgery.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective:To study the feasibility of design and harvest of free medial sural artery perforator flap with the "two-point and two-line method".Methods:From September 2022 to June 2023, Suzhou Ruihua Orthopaedic Hospital implemented the "two-point and two-line method" to guide preoperative perforator positioning and flap design. Thirty medial sural artery perforator flaps were successfully harvested with the method, and 21 wounds of hand and 9 of foot and ankle were reconstructed with the flaps. The size of soft tissue defects were 2.5 cm×2.5 cm-7.0 cm×14.5 cm, and the flaps size were 3.0 cm×3.0 cm-7.5 cm×15.0 cm. All donor sites were directly closed or by skin grafting. All patients were entered in 6-15 months of postoperative outpatient follow-up, and the recovery of donor and recipient sites was assessed by the comprehensive evaluation scales. The sensory function of the flaps was evaluated using the sensory function evaluation standard of British Medical Research Council (BMRC).Results:All perforators were successfully located with 47 perforators in total, and all of them were musculocutaneous perforator. It was found that there was 1 perforator in 14 flaps, 2 perforators in 15 flaps and 3 perforators in 1 flap. All 30 flaps survived after surgery, beside 2 flaps that had arterial insufficiency but survived successfully after surgical exploration. All donor sites healed in one stage. Comprehensive evaluation scale of flap was employed to evaluate the flaps and the scores were 84 points to 96 points with an average score of 92.5 points. The excellent and good grades were achieved in 27 flaps and 3 flaps, respectively, with a combined excellent and good rate at 100%. Sensation of the flaps was evaluated by BMRC with 1 flap of S 1, 17 of S 2 and 12 of S 3. Conclusion:The "two-point and two-line method" has been used in design of the perforator flap of medial sural artery. This method is simple and accurate, and is feasible and ideal in design of flaps before surgery.

Background::Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD).Methods::In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.Results::Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age ( P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0%-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%-18.6%) for their additive interaction in women. Conclusions::Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

Objective:To introduce the application of highly selective arterial indocyanine green angiography (hereinafter referred to as highly selective arterial angiography) in the design of anterolateral thigh free flap.Methods:This study was a retrospective observational study. From November 2023 to April 2024, 29 patients with wounds in extremities which were repaired by anterolateral thigh free flaps designed under the assistance of highly selective arterial angiography and met the inclusion criteria were admitted to the Department of Hand Surgery and Department of Wound Repair Surgery of Suzhou Ruihua Orthopedic Hospital, including 26 males and 3 females, aged 16 to 71 years. The wound area after debridement ranged from 8.0 cm×4.5 cm to 27.0 cm×16.0 cm. During the surgery, highly selective arterial angiography was used to assist in flap design. The fluorescence development range of the source arteries or perforators of flaps was observed. The blood supply range of the source arteries or perforators of flaps was determined based on the fluorescence development of the skin, and the excision position of the flap was adjusted. The flap incision area ranged from 9.0 cm×6.0 cm to 29.0 cm×16.0 cm. During the surgery, the number of highly selective arterial angiography, the type of source artery of perforators for puncture, and changes in the excision position of flaps were observed and recorded. After surgery, the blood supply and survival of flaps, the healing of wounds and the survival of skin grafts in the flap donor sites, and the angiography-related complications were observed.Results:All the 32 flaps of 29 patients were successfully excised. The highly selective arterial angiography was performed 37 times, including 13 cases of puncture of the oblique branch of the lateral circumflex femoral artery, 6 cases of puncture of the descending branch, 8 cases of double puncture of the oblique and descending branches, and 2 cases of puncture of arteries from other branches. During the surgery, the excision position of 28 flaps did not change, the excision position of 3 flaps moved towards proximal extremity of the thigh, and the excision position of 1 flap moved towards distal extremity of the thigh. All the flaps survived successfully after the surgery, and there was no partial necrosis of the flaps at the proximal or distal ends. The wounds in the flap donor sites healed, and all skin grafts survived. No angiography-related complications occurred.Conclusions:Highly selective arterial angiography can be used to determine the blood supply range of the source artery and perforators of the anterolateral thigh free flaps during the surgery. It can evaluate the blood supply of flaps more intuitively and objectively. Its application in assisting flap design can avoid partial flap necrosis caused by unreasonable preoperative design to a certain extent, and it is safe and reliable.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*

Objective:To explore the distribution characteristics of the perforators of the oblique branch of the lateral circumflex femoral artery, and to report the clinical effect of the anterolateral thigh flap pedicled with the oblique branch in repairing the wounds of the extremities.Methods:The clinical data of the patients with anterolateral thigh flap pedicled with oblique branch of lateral circumflex femoral artery in Suzhou Ruihua Orthopaedic Hospital from December 2020 to April 2021 were analyzed retrospectively. High frequency color Doppler ultrasound was used to detect the large perforators of the oblique branch of the lateral circumflex femoral artery near the midpoint of the line between the anterior superior iliac spine and the lateral margin of the patella. With reference to the location of the perforators, according to the size and shape of the defect in the recipient area, the anterolateral thigh flap pedicled with oblique branch was designed and dissected to repair the wound. During the operation, the distance between the emitting point of the main oblique branch, the skin entry point of the perforators and the anterior superior iliac spine was measured with a steel ruler, the diameter of the perforators was measured with a microscale, and the number of perforators was counted. The survival and complications of the flap were observed and followed up after operation. In the last follow-up, the comprehensive evaluation scale was used to evaluate the repair effect: 90 to 100 points is excellent, 75 to 89 points is good, 60 to 74 points is average, and less than 60 points is poor.Results:A total of 84 patients were included, including 62 males and 22 females, aged from 14 to 82 years (mean 46.9 years), including 32 cases of hand wounds, 6 cases of forearm wounds, 3 cases of upper arm wounds, 10 cases of calves and 33 cases of foot and ankle wounds. The wound area was 6 cm × 4 cm-20 cm × 45 cm. A total of 88 flaps were removed in 84 patients (skin flaps on both thighs were removed in 4 patients). The size of the skin flap of 88 thighs was 7 cm × 5 cm-37 cm × 11 cm, of which 85 sides of 82 cases survived completely. One case of diabetes had complete necrosis 1 month after operation, and 1 case of 34 cm had necrosis of the distal end of 3 cm × 3 cm skin flap. Necrotic skin flaps were repaired with skin grafting. Four patients developed arterial crisis within 24 hours after operation, and those flaps survived after surgical exploration. All donor areas healed. During the follow-up of 6 to 9 months, the shape of the recipient area was normal in all patients, and there was no deep tissue infection such as osteomyelitis. The color and texture of all flaps were good. The sensation returned to S1-S2 after operation. The skin flap comprehensive evaluation scale was used to evaluate the repair effect. The patients’ score ranged from 73 to 94 points, with an average of 88.1 points. Including 33 excellent cases, 46 good cases and 5 average cases, the excellent and good rate was 94.0%(79/84). A total of 215 perforators were marked with 88 flaps before operation, and 208 perforators were found during the operation(the diameter of the perforators was 0.4-1.5 mm), of which 130 were sent out by oblique branches. There were perforators of the oblique branch in all flaps, with an average of 1.5 on each side, including 84(64.6%) septocutaneous perforators and 46(35.4%) musculocutaneous perforators. Most of the oblique branches originate from the lateral circumflex femoral artery, which runs in the intermuscular septum between the rectus femoris and the intermediate femoris muscle. It is divided into deep branches and superficial branches at the middle and upper 1/3 junction of the line between the anterior superior iliac spine and the lateral margin of the patella. The skin perforators of the oblique branch of the lateral circumflex femoral artery is mostly sent out from the superficial branch, and there are 118 perforators located at the midpoint and proximal end of the line between the anterior superior iliac spine and the lateral margin of the patella, accounting for 90.8% (118/130), reaching a peak at 0.4 (there are 37 perforators).Conclusion:The oblique branch of the lateral circumflex femoral artery is relatively constant, and most of the perforators are located near the midpoint of the line between the anterior superior iliac spine and the lateral margin of the patella, and the proportion of septocutaneous perforator is high. The distribution of perforator is regular, the blood supply is reliable, the application mode is flexible, and the donor site position is more concealed while the blood supply of the flap is secured.