The incidence of knee osteoarthritis(KOA)is in-creasing year by year,seriously affecting patients'health.Mes-enchymal stem cells are multipotent cells with multiple differen-tiation functions.The extracellular vesicles released by these cells can carry various"cargo"to corresponding cells and tis-sues,exerting biological functions.They have shown great clini-cal potential in the treatment of KOA.This study reviews the therapeutic effects and mechanisms of extracellular vesicles se-creted by mesenchymal stem cells from different tissues such as bone marrow,adipose tissue,and synovium in KOA.It is found that miRNA is an important biological component in exerting therapeutic effects.The study also discusses the research pro-gress of engineered extracellular vesicles in KOA,pointing out the current challenges in clinical application,such as standard-ized acquisition of extracellular vesicles and difficulties in targe-ted action,aiming to provide a certain reference for the basic re-search and clinical application of extracellular vesicle therapy for KOA.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective: To introduce a classification of alar retraction, and to discuss the therapeutic strategy of alar retraction with cartilage graft and the satisfaction evaluation of patients after operation. Methods: A retrospective analysis was performed on 88 patients with alar retraction admitted to the Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University from January 2015 to December 2020, including 20 males and 68 females, aged 20 to 48 years, with an average age of 28.98 years. All patients underwent external rhinoplasty according to a series of treatment plans determined by the classification of alar retraction based on nostril exposure. Visual Analogue Scale (VAS) and Rhinoplasty Outcomes Evaluation (ROE) were used to conduct satisfaction survey before and 12 months after operation. Wilcoxon signed-rank test was used to analyze patient satisfaction. Results: A total of 88 patients were included in this study. According to the classification of alar retraction based on nostril exposure, 45 cases were mild, 23 cases were moderate, and 20 cases were severe. There were 16 cases of unilateral and 72 cases of bilateral alar retraction. The patients were followed up for 12 to 18 months, with an average of 13.37 months. The VAS score and ROE score after each type of surgery were higher than those before surgery, with statistically significant (all P<0.05). Among them, the difference in VAS score (6.75±1.29) and in ROE satisfaction (67.70±7.38) of patients with severe alar retraction were the most significant improvement. Conclusion: The classification of alar retraction based on nostril exposure in the frontal view can comprehensively evaluate the severity of alar retraction, and makes the treatment algorithms systematic and comprehensive. The satisfaction of patients is relatively high.
Male ; Female ; Humans ; Adult ; Rhinoplasty ; Retrospective Studies ; Patient Satisfaction ; Treatment Outcome ; Esthetics ; Nose/surgery*

Objective:To investigate the effect of right stellate ganglion block (RSGB)-serratus anterior plane block (SAPB) combined with general anesthesia in thoracoscopic radical resection of lung cancer.Methods:A total of 90 patients who planned to undergo thoracoscopic radical resection of lung cancer in Xiangya Changde Hospital from March 2020 to September 2021 were prospectively selected and divided into 3 groups by random number table method: general anesthesia group (G group), (SAPB)+ general anesthesia group (SG group), RSGB+ SAPB+ general anesthesia group (RSG group), 30 cases in each group. The SG group received SAPB on the operative side before general anesthesia, and the RSG group received RSGB+ SAPB on the operative side before general anesthesia. After the blocking effect was determined, all patients were given general anesthesia in the same scheme according to their weight, and patients were given patient-controlled intravenous analgesia (PCIA) after surgery. The mean arterial pressure (MAP) and heart rate (HR) were recorded before anesthesia (T 0), before intubation (T 1), 1 min after intubation (T 2), 5 min after intubation (T 3), at extubation (T 4) and 5 min after extubation (T 5). The intraoperative dosage of remifentanil, incidence of nausea and vomiting (PONV) within 24 hours after surgery, number of additional PCIA within 24 hours, the Visual Analogue Scale (VAS) of static and dynamic pain, the Bruggrmann Comfort Scale (BCS) and Richard Campbell Sleep Questionnaire (RSCQ) 24 hours after surgery were recorded. Results:Compared with T 0, the MAP and HR in 3 groups were increased 1 min after intubation (T 2) and at extubation (T 4), but the increases in RSG group were significantly less than those in G and SG groups (all P<0.05). The remifentanil dosage, PONV incidence and PCIA supplemental times in SG and RSG groups were less than those in G group, and the BCS score and RSCQ score were higher than those in G group (all P<0.05); the BCS score and RSCQ score in RSG group were higher than those in SG group (all P<0.05). Conclusions:RSGB+ SAPB combined with general anesthesia in thoracoscopic radical resection of lung cancer has little circulation fluctuation, good postoperative analgesia effect, less adverse reactions and high comfort level.

Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T⁺tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.
Mice ; Animals ; NF-kappa B ; Myeloid Differentiation Factor 88/metabolism* ; Lipopolysaccharides/pharmacology* ; Toll-Like Receptor 4/metabolism* ; Autistic Disorder/metabolism* ; Signal Transduction/physiology*

To investigate the effect of inactivated new tu-berculosis vaccine strain(B/R strain)on immune memory of T lymphocytes in mice,C57BL/6 mice were immunized with PBS,BCG strain,B/R strain and inactivated B/R strain.At week 9,12 and 15 after immunization,the spleens of each group were taken,and the spleen lymphocytes were extracted.Half of the spleen lymphocytes in each group were directly de-tected,and the rest were cultured in vitro and stimulated with PPD according to the experimental design.Flow cytometry was used to detect the number of central memory T cells(TCM)and effector memory T cells(TEM)in spleen lymphocytes of uns-timulated and stimulated mice.Without PPD stimulation after immunization,the CD4+TCM(F=13.20,P＜0.05)and CD4+TEM(F=28.15,P＜0.05)induced by inactivated B/R group,B/R group and BCG group was higher than that of PBS group at week 9.The induced CD8+TCM(F=8.92,P＜0.05)and CD8+TEM(F=6.13,P＜0.05)was higher than that of PBS group.At week 12,the CD4+TCM(F=15.97,P＜0.05)and CD4+TEM(F=13.60,P＜0.05)induced by each group was higher than that of PBS group.The induced CD8+TCM(F=5.52,P＜0.05)and CD8+TEM(F=20.15,P＜0.05)was higher than that of PBS group.At week 15,the CD4+TCM(F=15.40,P＜0.05)and CD4+TEM(F=7.43,P＜0.05)induced by each group was higher than that of PBS group.The induced CD8+TCM(F=6.57,P＜0.05)and CD8+TEM(F=9.27,P＜0.05)was higher than that of PBS group.At week 9,the CD4+TCM(F=9.66,P＜0.05)and CD4+TEM(F=11.20,P＜0.05)induced by inacti-vated B/R group,B/R group and BCG group was higher than that of PBS group.The induced CD8+TCM(F=7.24,P＜0.05)and CD8+TEM(F=9.30,P＜0.05)was higher than that of PBS group.At week 12,the CD4+TCM(F=9.33,P＜0.05)and CD4+TEM(F=6.94,P＜0.05)induced by each group was higher than that of PBS group.The induced CD8+TCM(F=67.71,P＜0.05)and CD8+TEM(F=10.86,P＜0.05)was higher than that of PBS group.At week 15,the CD4+TCM(F=39.88,P＜0.05)and CD4+TEM(F=11.93,P＜0.05)induced by each group was higher than that of PBS group.The induced CD8+TCM and CD8+TEM(F=38.47,P＜0.05)was higher than that of PBS group(F=138.80,P＜0.05).It is worth noting that at week 15,the CD8+TCM(qinactivated B/R=12.24,qB/R=12.61,P＜0.05)and CD8+TEM(qinactivated B/R=7.19,qB/R=5.00,P＜0.05)induced by inactivated B/R group and B/R group were higher than those of BCG group.The immunizing mice with inactivated B/R strain,the ability of inducing immune memory of T lymphocytes in mice was equivalent to that of B/R strain.Heat-inacti-vation did not affect the ability of B/R strain to induce immune memory in mice.

Objective:To analyze the effect of transtracheal pressure (TTP) on the application of a speaking valve in critically ill patients after tracheostomy.Methods:A retrospective analysis was conducted of 50 patients wearing a speaking valve after tracheostomy. Patients who had been wearing a speaking valve for 30min or more were the tolerance group, while those with less than 30min were the intolerance group. Transtracheal pressure was monitored during resting breathing, forced expiration and speaking. Linear regression models were evaluated to isolate the factors best predicting tolerance. The changes in respiratory muscle contraction before and after wearing a speaking valvs were evaluated using ultrasound. The patients′ satisfaction with wearing a speaking valve was also recorded.Results:TTP during speaking significantly predicted tolerance. The baseline values of diaphragmatic thickening fraction and physical functioning also positively predicted tolerance. Acute physiology and chronic health (APACHE II) score was a significant negative predictor. After wearing the speaking valve, the average contraction of the rectus abdominis, external oblique, internal oblique and transverse abdominis muscles increased significantly. Both groups expressed high satisfaction with the speaking valves.Conclusions:Transtracheal pressure during speaking can help predict the tolerance for wearing a speaking valve among critically ill patients after a tracheostomy. Baseline diaphragmatic thickening fraction, physical functioning and APACHE II score can predict the duration of speaking valve tolerance.

Objective:To explore the possible mechanism of electroacupuncture to improve detrusor hyperreflex after suprasacral spinal cord injury. Methods:A total of 60 female Sprague-Dawley rats were included. According to the random number table, twelve were selected as the blank group, twelve as the sham operation group, and the remaining 36 were made neurogenic bladder models using modified T₁₀ spinal cord transection. After that, twelve of them were randomly selected as the model group and twelve were as the electroacupuncture group from the model rats that met the requirements. On the 19th day after modelling, Ciliao (BL32), Zhongji (RN3) and Sanyinjiao (SP6) were taken for electroacupuncture. After seven days of continuous treatment, urodynamic testing was performed, content of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in detrusor was determined by ELISA, and the level of phosphorylation of myosin light chain kinase (p-MLCK) of detrusor was determined by Western blotting. Results:Compared with the blank group and the sham operation group, the maximum bladder capacity and bladder compliance significantly reduced (P < 0.01), and the base pressure and leakage point pressure of bladder significantly increased (P < 0.01); the content of cAMP and PKA in detrusor reduced (P < 0.01), p-MLCK in detrusor reduced (P < 0.05) in the model group. Compared with the model group, the maximum bladder capacity and bladder compliance increased (P < 0.01), the base pressure of the bladder and the pressure at the leak point decreased (P < 0.05); the contents of cAMP and PKA protein in detrusor increased (P < 0.05), the p-MLCK in detrusor increased (P < 0.05) in the electroacupuncture group. Conclusion:Electroacupuncture at Ciliao, Zhongji and Sanyinjiao points could improve the bladder function of rats with detrusor hyperreflex after complete spinal cord injury, and its mechanism may be related to up-regulating the expression of cAMP and PKA, phosphorylating and inactivating p-MLCK, which promote relaxation of detrusor.

OBJECTIVE: To analyze the risk factors affecting prognosis of children with hemophagocytic lymphohistiocytosis (HLH). METHODS: The clinical manifestations and laboratory data of 143 HLH children who met the HLH-2004 diagnostic criteria in Shenzhen Children's Hospital from January 2009 to May 2017 were retrospectively analyzed, and the independent factors affecting prognosis were also analyzed. RESULTS: The median age of 143 HLH children was 1.9 (0.1-14.3) years old, and the median follow-up time was 6.7 years (1 day - 11.9 years). The overall survival rate of 1 month, 1 year, and 10 years was (87.4±5.5)%, (81.1±6.5)%, and (81.1±6.5)%, respectively. The deaths occurred within 1 year after onset. Multivariate analysis showed that central nervous system (CNS) involvement (P=0.047), low hemoglobin (P=0.002), prolonged activated partial thromboplastin time (APTT) (P<0.001), high triglyceride (P=0.005) were all the independent risk factors affecting survival of the children. Receiver operating characteristic curve indicated that APTT (AUC=0.753, P<0.001) was more valuable than other risk factors in predicting death of the children. The cut-off value of APTT was 56.6 s, and the sensitivity and specificity of which was 55.6% and 89.7%, respectively. CONCLUSION Hypohemoglobinemia, prolonged APTT, hypertriglyceridemia, and CNS involvement the risk factors affecting prognosis of HLH, and prolonged APTT shows a strong predictive value for death.
Adolescent ; Child ; Child, Preschool ; Humans ; Infant ; Lymphohistiocytosis, Hemophagocytic ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Rate

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method ; Follow-Up Studies ; Humans ; Ointments ; Psoriasis/drug therapy* ; Resorcinols ; Severity of Illness Index ; Stilbenes ; Treatment Outcome