Objective:To evaluate the clinical efficacy of the Masquelet technique (induced membrane technique) combined with an antibiotic-impregnated bone cement-coated plate for the treatment of infected nonunion following internal fixation of clavicle fractures.Methods:A retrospective analysis was conducted on 12 patients with clavicular infected nonunion who underwent staged treatment using the Masquelet technique combined with an antibiotic-loaded bone cement-coated plate between May 2021 and May 2023 in the Second Ward of Traumatic Orthopedics at Gansu Provincial People's Hospital. The cohort included 8 males and 4 females, with a mean age of 28.8±3.1 years (range: 12-48 years). Among them, 10 cases had mid-third clavicular defects, and 2 cases had lateral third defects. All 12 cases involved nonunion due to bone infection following internal fixation of clavicle fractures, with 6 cases initially fixed with Kirschner wires and 6 with plates. The induced membrane technique was applied in two stages. Stage One: Radical debridement was performed, including removal of the original internal fixation and infected necrotic tissue. A plate was implanted, and the bone defect area was filled with antibiotic-loaded bone cement, fully encapsulating the plate. Stage Two: Bone graft reconstruction was carried out 6-8 weeks later, after infection control was confirmed. The induced membrane was incised, the bone cement was removed, and a bone graft was placed within the membrane. Outcomes included infection control, bone union time, pain visual analogue scale (VAS), and Constant-Murley shoulder score (CMS) at the final follow-up.Results:The interval between the first and second surgeries was 7.42±1.17 weeks (range: 6-10 weeks). All 12 patients were followed up for a mean duration of 16.4±3.9 months (range: 12-24 months). One patient experienced recurrent infection after the first-stage surgery, which was controlled after repeat debridement and replacement of antibiotic-loaded bone cement, with no recurrence during follow-up. All 12 patients achieved bony union, with a mean healing time of 3.42±0.67 months (range: 3-5 months). Radiographs showed continuous bone cortex with no visible fracture lines. At the final follow-up, the mean VAS score was 0.42±0.51, significantly lower than the preoperative score of 6.68±1.12 ( t=18.711, P<0.001). The mean CMS score was 88.93±3.94, significantly higher than the preoperative score of 44.41±7.15 ( t=20.786, P<0.001). Conclusion:The Masquelet technique combined with an antibiotic-loaded bone cement-coated plate is effective in treating infected nonunion after internal fixation of clavicle fractures, significantly improving acromioclavicular joint function.

ObjectiveTo investigate the protective effect of Xielitang on dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） mice and its possible mechanism. MethodsDSS was used to establish UC model. Sixty mice were randomly divided into a normal group， a model group， a sulfasalazine group （0.6 g·kg^-1）， and low-， medium-， and high-dose Xielitang groups （1.67， 3.34， 6.68 g·kg^-1）. After treatment for 42 d， the colon length was recorded， and the disease activity index （DAI） score was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10）. Hematoxylin-eosin （HE） staining was used to observe the pathomorphological changes of colon. Western blot was used to detect the protein expression of farnesoid X receptor （FXR）， small heterodimer partner （SHP）， liver receptor homolog-1 （LRH-1）， cholesterol 7α-hydroxylase （CYP7A1）， and fibroblast growth factor receptor 4 （FGFR4） in liver and FXR， sodium-dependent bile acid transporter （ASBT）， and fibroblast growth factor 15 （FGF15） in ileum. 16S rRNA sequencing was used to analyze the intestinal flora. Moreover， ultra-high performance liquid chromatography–tandem mass spectrometry was used to detect the bile acid content. ResultsCompared with the normal group， the model group showed significantly decreased colon length， IL-10 content， α-diversity index， abundance of Firmicutes and Lactobacillus， and content of deoxycholic acid （DCA） and lithocholic acid （LCA） （P<0.01）， significantly increased DAI score， IL-6 and TNF-α content， abundance of Bacteroidetes， and the content of cholic acid （CA）， chenodeoxycholic acid （CDCA）， and taurocholic acid （TCA） （P<0.05， P<0.01）， significantly down-regulated protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and significantly up-regulated protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. In addition， the structure of colonic mucosa was destroyed， and inflammatory cells infiltrated in the model group. Compared with the model group， Xielitang could significantly increase the colon length， IL-10 content， α-diversity index， the abundance of Firmicutes and Lactobacillus， and DCA and LCA content （P<0.05， P<0.01）， decrease DAI score， abundance of Bacteroidetes， and the content of IL-6， TNF-α， CA， CDCA， and TCA （P<0.01）， up-regulate the protein expression of FXR， SHP， and FGFR4 in liver and FXR， ASBT， and FGF15 in ileum （P<0.01）， and down-regulate the protein expression of LRH-1 and CYP7A1 in liver （P<0.01）. The pathological damage of colonic mucosa was obviously alleviated. ConclusionXielitang protects against UC probably by regulating the "intestinal microbiota-bile acid" axis， regulating intestinal flora imbalance， and maintaining bile acid homeostasis.

Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

Objective:To evaluate the clinical efficacy of the Masquelet technique (induced membrane technique) combined with an antibiotic-impregnated bone cement-coated plate for the treatment of infected nonunion following internal fixation of clavicle fractures.Methods:A retrospective analysis was conducted on 12 patients with clavicular infected nonunion who underwent staged treatment using the Masquelet technique combined with an antibiotic-loaded bone cement-coated plate between May 2021 and May 2023 in the Second Ward of Traumatic Orthopedics at Gansu Provincial People's Hospital. The cohort included 8 males and 4 females, with a mean age of 28.8±3.1 years (range: 12-48 years). Among them, 10 cases had mid-third clavicular defects, and 2 cases had lateral third defects. All 12 cases involved nonunion due to bone infection following internal fixation of clavicle fractures, with 6 cases initially fixed with Kirschner wires and 6 with plates. The induced membrane technique was applied in two stages. Stage One: Radical debridement was performed, including removal of the original internal fixation and infected necrotic tissue. A plate was implanted, and the bone defect area was filled with antibiotic-loaded bone cement, fully encapsulating the plate. Stage Two: Bone graft reconstruction was carried out 6-8 weeks later, after infection control was confirmed. The induced membrane was incised, the bone cement was removed, and a bone graft was placed within the membrane. Outcomes included infection control, bone union time, pain visual analogue scale (VAS), and Constant-Murley shoulder score (CMS) at the final follow-up.Results:The interval between the first and second surgeries was 7.42±1.17 weeks (range: 6-10 weeks). All 12 patients were followed up for a mean duration of 16.4±3.9 months (range: 12-24 months). One patient experienced recurrent infection after the first-stage surgery, which was controlled after repeat debridement and replacement of antibiotic-loaded bone cement, with no recurrence during follow-up. All 12 patients achieved bony union, with a mean healing time of 3.42±0.67 months (range: 3-5 months). Radiographs showed continuous bone cortex with no visible fracture lines. At the final follow-up, the mean VAS score was 0.42±0.51, significantly lower than the preoperative score of 6.68±1.12 ( t=18.711, P<0.001). The mean CMS score was 88.93±3.94, significantly higher than the preoperative score of 44.41±7.15 ( t=20.786, P<0.001). Conclusion:The Masquelet technique combined with an antibiotic-loaded bone cement-coated plate is effective in treating infected nonunion after internal fixation of clavicle fractures, significantly improving acromioclavicular joint function.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

The incidence of early-onset gastric cancer (EOGC) is consistently increasing, and its etiology is notably complex. This increase may be attributed to distinctive factors that differ from those associated with late-onset gastric cancer (LOGC), including genetic predispositions, dietary factors, gastric microbiota dysbiosis, and screening of high-risk cases. These factors collectively contribute to the onset of cancer. EOGC significantly differs from LOGC in terms of clinicopathological and molecular characteristics. Moreover, multiple differences in prognosis and clinical management also exist. This study aimed to systematically review the latest research advancements in the epidemiological characteristics, etiological factors, clinicopathological and molecular features, prognosis, and treatment modalities of EOGC.

Objective To investigate the feasibility and early efficacy of transapical transcatheter aortic valve replacement (TAVR) combined with transcatheter mitral valve edge-to-edge repair (TEER) in patients with high-risk aortic valve lesions combined with severe mitral regurgitation. Methods The clinical data of patients who underwent "one-stop" transapical TAVR+TEER in our hospital from August 2022 to October 2023 were retrospectively analyzed. Results Five patients were collected, including 3 males and 2 females with a mean age of 66.6±1.8 years. Four patients had aortic valve insufficiency combined with mitral regurgitation and one had aortic valve stenosis and insufficiency combined with mitral regurgitation. All patients successfully completed transapical TAVR+TEER, and the immediate postoperative echocardiographic results revealed that none of them had more than mild perivalvular leakage and mitral regurgitation, and the prosthetic valves were in good position and function. At 1 week postoperatively, echocardiographic results showed 5 patients with no displacement of the prosthetic valve, detachment of the mitral clip, or damage to the leaflets. At 1 month postoperatively, cardiac function was improved to varying degrees in 4 patients, and 1 patient died of multiorgan failure. At 2 months postoperatively, 1 patient died of cerebrovascular accident, and at 3 months postoperatively the echocardiographic results of the remaining 3 patients revealed that there was no more than mild perivalvular leakage or mitral regurgitation, and the patients' postoperative cardiac function and daily life ability were significantly improved. Conclusion In high-risk aortic valve lesions combined with severe mitral regurgitation, "one-stop" transapical TAVR+TEER is feasible with favorable early efficacy and safety.

Objective:The neurovascular unit(NVU)damage in rats with cerebral ischemia-reperfusion injury(CI-RI)was evaluated based on multimodal MRI combined with multiple histological techniques to provide visual evidence for clinical assessment of CIRI.Methods:28 healthy male Sprague-Dawley rats were randomly divided into sham-oper-ated(Sham)group and CIRI group.At 24 h after modeling,rats underwent head T2-weighted imaging,diffusion-weighted imaging,water extraction with phase-contrast arterial spin labeling magnetic resonance imaging(MRI),and cerebral blood bleeding oxygen monitoring.Hematoxylin-eosin(HE)staining was used to observe the morphological changes of nerve cells in cerebral cortex.Immunofluorescence staining and transmission electron microscopy were used to observe the changes of NVU after CIRI.The endothelial tight junction proteins(claudin-5 and ZO-1)and matrix metalloproteinase-9(MMP-9)were detected by immunohistochemical staining and Western Blot analysis,to evaluate blood-brain-barrier(BBB)disruption in CIRI rats.Results:The MRI results showed that the brain tissue of the CIRI group was edematous,and the blood perfusion significantly decreased and the BBB permeability significantly increased compared with that of the Sham group(P＜0.01).The results of cerebral blood hemoglobin oxygen monitoring showed that the hemoglobin oxygen saturation of the cerebral cortex on the injured side was significantly lower than that of the Sham group(P＜0.05).HE staining showed the neuronal cells of the injured cerebral cortex were disordered and the nuclei shrank.Immunofluorescence staining results showed the number of NeuN and CD31 positive cells in the cerebral cortex of the injured side was significantly lower than that in the Sham group(P＜0.01),and the number of TUNEL positive cells in the cerebral cortex and striatum was significantly higher than that in the Sham group(P＜0.05).Transmission electron microscopy revealed the tight junctions of cerebral cortical endothelial cells were damaged,neuro-nal nucleus contraction,and astrocyte body edema.Immunohistochemical staining showed that the number of claudin-5 and ZO-1 positive cells in the cerebral cortex on the injured side was significantly lower than that in the Sham group,and the expression of MMP-9 was significantly higher than that in the Sham group(P＜0.01).Conclusion:CIRI re-sults in NVU injury,BBB disruption,and exacerbation of brain damage in rats.Multimodal MRI combined with various histopathological techniques effectively assesses NVU injury after CIRI.

Objective:The neurovascular unit(NVU)damage in rats with cerebral ischemia-reperfusion injury(CI-RI)was evaluated based on multimodal MRI combined with multiple histological techniques to provide visual evidence for clinical assessment of CIRI.Methods:28 healthy male Sprague-Dawley rats were randomly divided into sham-oper-ated(Sham)group and CIRI group.At 24 h after modeling,rats underwent head T2-weighted imaging,diffusion-weighted imaging,water extraction with phase-contrast arterial spin labeling magnetic resonance imaging(MRI),and cerebral blood bleeding oxygen monitoring.Hematoxylin-eosin(HE)staining was used to observe the morphological changes of nerve cells in cerebral cortex.Immunofluorescence staining and transmission electron microscopy were used to observe the changes of NVU after CIRI.The endothelial tight junction proteins(claudin-5 and ZO-1)and matrix metalloproteinase-9(MMP-9)were detected by immunohistochemical staining and Western Blot analysis,to evaluate blood-brain-barrier(BBB)disruption in CIRI rats.Results:The MRI results showed that the brain tissue of the CIRI group was edematous,and the blood perfusion significantly decreased and the BBB permeability significantly increased compared with that of the Sham group(P＜0.01).The results of cerebral blood hemoglobin oxygen monitoring showed that the hemoglobin oxygen saturation of the cerebral cortex on the injured side was significantly lower than that of the Sham group(P＜0.05).HE staining showed the neuronal cells of the injured cerebral cortex were disordered and the nuclei shrank.Immunofluorescence staining results showed the number of NeuN and CD31 positive cells in the cerebral cortex of the injured side was significantly lower than that in the Sham group(P＜0.01),and the number of TUNEL positive cells in the cerebral cortex and striatum was significantly higher than that in the Sham group(P＜0.05).Transmission electron microscopy revealed the tight junctions of cerebral cortical endothelial cells were damaged,neuro-nal nucleus contraction,and astrocyte body edema.Immunohistochemical staining showed that the number of claudin-5 and ZO-1 positive cells in the cerebral cortex on the injured side was significantly lower than that in the Sham group,and the expression of MMP-9 was significantly higher than that in the Sham group(P＜0.01).Conclusion:CIRI re-sults in NVU injury,BBB disruption,and exacerbation of brain damage in rats.Multimodal MRI combined with various histopathological techniques effectively assesses NVU injury after CIRI.

Objective:To explore the clinical efficacy of adult donor dual kidney transplantation.Methods:Retrospective analysis of case data of 13 adult donor kidney dual kidney transplantation (DKT) performed in the The Second Xiangya Hospital of Central South University from September 2016 to December 2020. For 13 donors, the average age and BMI were (53.5±12.4)years and (24.3±2.8) kg/m 2, respectively. Their mean Serum creatinine (SCr) at admission and before procurement was (132.9±54.1)and (228.7±112.4)μmol/L, respectively. 3 of them had diabetes mellitus history, and 8 had hypertension history. 11 met the United Network for Organ Sharing (UNOS) DKT criteria and 6 met Remuzzi score DKT criteria. For 13 recipients, the average age and BMI were (39.3±8.9)years and (20.2±2.4)kg/m 2, respectively. All of them received ABO blood type-matched kidney transplants. 2 of them had their grafts transplanted in the bilateral iliac. In 12 cases, the grafts filled rapidly and urinated immediately when opening blood flow. In 1 case, the grafts were dark in color and vascular showed weak pulsation after opening blood flow. The time to recovery of perioperative graft function (from the day of surgery to the natural reduction of SCr to the normal range 44-133μmol/L), the occurrence of delayed graft function (DGF), acute rejection (AR), ureteral and surgical incision complications, as well as the recipients’ final follow-up SCr, eGFR, urinary protein, and grafts outcome were observed. Risk factors affecting outcomes were assessed by univariate logistic regression analysis. Results:The SCr dropped to the normal range at discharge in 10 recipients, and the average recovery time was (13.8±13.0) days. In other 3 cases SCr at discharge were 300.0, 149.0, 152.5μmol/L. 4 cases had DGF, 4 had AR, 1 experienced urinary fistula, and 1 experienced incisional dehiscence, which were treated with anti-rejection, J-tube implantation, continuous catheterization to maintain bladder void, secondary suturing, respectively. The follow-up time ranged from 4 to 54 months, with a median of 28(15.5, 31.0) months. At the final follow-up time, 10 cases had good graft function, 2 suffered impaired kidney function, and 1 experienced graft failure. The average SCr and eGFR except for graft failure patient were (144.2±101.3)μmol/L and (52.9±21.2)ml/min, respectively. 4 had positive urine protein. Univariate logistic regression analysis showed that donor age, BMI, history of diabetes mellitus and hypertension, and SCr were not significantly correlated with recipients’ DGF and graft impairment ( P>0.05), and due to the small sample size, multifactorial logistic regression analysis was not performed. Conclusion:The short to medium-term effects of adult donor DKT coule be safe and feasible.