Identification, influencing factors and outcomes of time delays in the management pathway of diabetic foot: A systematic review.

OBJECTIVE: A systematic review was conducted to evaluate the time delays in the management of diabetic foot and explore influencing factors of these delays and potential outcomes. METHODS: The researchers searched several electronic databases (Pubmed, Web of Science, Cochrane Library, EMbase, CNKI, WanFang, CBM and VIP) for English and Chinese studies that examined time delays in the management pathway of diabetic foot. Two authors independently screened and extracted data, and assessed the quality of the included studies using the Newcastle-Ottawa Scale and the Agency for Health Research and Quality checklist. Due to heterogeneity among the studies, descriptive analysis was performed. RESULTS: The review included 28 articles, comprising 20 cohort studies and 8 cross-sectional studies, that met the inclusion criteria. Among these, 14 were deemed of high quality. The median times from symptom onset to primary health care or specialist care varied from 3 to 46.69 days. The median delay in referral by primary care specialists ranged from 7 to 31 days, and subsequent median times to definitive treatment ranged from 6.2 to 56 days. Multiple complex factors were found to contribute to these delays, including patient demographics (older age, lower education level and income level) and poor patient health-seeking behaviors (inaccurate self-treatment, incorrect recognition and interpretation of symptoms), inaccurate assessment or initial treatment by health primary professionals, complex referral pathways and clinical characteristics of diabetic foot (number of foot ulcers, Wagner grade scale, and hemoglobin A1c index). Negative outcomes associated with these delays included increased risk of major amputation and mortality, decreased wound healing rate, prolonged hospital stay, and increased hospital costs. CONCLUSIONS: Time delays in the diabetic foot management pathway were both common and serious, contributing to negative health outcomes for patients with diabetic foot. Many complex factors related to patient's poor patient health-seeking behaviors, health system, and clinical characteristics of diabetic foot are responsible for these delays. Therefore, it is necessary to develop new strategies for standard referral practices and strengthen patient awareness of seeking care.

Positive effects of neuroligin-1,-2 on oligodendrocyte differentiation and myelination / 解剖学报

Objective To investigate the effects of neuroligin-1,-2(NLGN-1,-2)on oligodendrocyte(OLs)differentiation and myelination in the central nervous system.Methods OLs were cultured in vitro in the presence of different concentrations of NLGN-1 and NLGN-2.Morphological differentiation of OLs was observed by immunofluorescent staining and mRNA expression levels of myelin-associated genes were detected by Real-time PCR.Western blotting was used to detect the expression of myelin-related proteins.Results NLGN-1,-2 accelerated the differentiation of oligodendrocyte precursor cells(OPCs)into mature OLs,and promoted the ability of myelin sheath formation.In vitro culture conditions,the dosage of 500 μg/L had the best promotion effect on OLs differentiation and maturation,and NLGN-2 had better promoting effect than that of NLGN-1.Furthermore,the mRNA expression levels of myelin-associated genes myelin protein P0(MPZ),myelin basic protein(MBP)increased after the neuroligins treatments detected by Real-time PCR.Western blotting result showed that the expressions of MBP and MPZ increased significantly after 500 μg/L treatment with NLGN-1 and NLGN-2 for 12 hours.Conclusion NLGN-1,-2 promote OLs differentiation and myelination.The positive effect of NLGN-2 is greater than that of NLGN-1 significantly,suggesting that the treatment with inhibitory synaptic-associated cytokines may improve the ability of myelin sheath formation in the central nervous system.

Relationship of miR-126 and miR-325 in serum and vitreous with the severity of proliferative vitreoretinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the relationship of miR-126 and miR-325 in serum and vitreous with the severity of proliferative vitreoretinopathy(PVR).METHODS: A total of 100 cases(100 eyes)with PVR who were treated in our hospital from October 2019 to October 2022 were selected and retrospectively studied. They were divided into a mild group(42 eyes)and a severe group(58 eyes)according to the degree of retinopathy, and another 30 cases(30 eyes)that underwent vitrectomy without retinopathy due to eye trauma in our hospital during the same period were selected as the control group. Fluorescence quantitative PCR was used to detect the expression levels of miR-126 and miR-325 in serum and vitreous; ELISA was used to detect the levels of transforming growth factor β(TGF-β), platelet-derived growth factor(PDGF), vascular endothelial growth factor(VEGF), and tumor necrosis factor α(TNF-α)in serum and vitreous; and Pearson's method was used to analyze the correlation between the serum and vitreous levels of miR-126 and miR-325 correlated with the levels of TGF-β, PDGF, VEGF, and TNF-α; Logistic multifactorial analysis was used to analyze the influencing factors for the occurrence of severe PVR.RESULTS: Compared with the control group, miR-126 levels in serum and vitreous of PVR patients were decreased and lower in the severe PVR group than in the mild PVR group(both P<0.05); miR-325 levels were increased and higher in the severe PVR group than in the mild PVR group(both P<0.05). TGF-β, PDGF, VEGF, and TNF-α levels in serum and vitreous were increased in the severe PVR group compared to the mild PVR group(all P<0.05). The miR-126 levels in serum and vitreous of patients with PVR were negatively correlated with miR-325, TGF-β, VEGF, TNF-α, and PDGF levels(all P<0.05), and miR-325 was positively correlated with TGF-β, VEGF, TNF-α, and PDGF levels(all P<0.05). Logistic regression analysis showed that miR-325, TGF-β, PDGF, and TNF-α were all independent risk factors for the development of severe PVR in serum and vitreous, and miR-126 was an independent protective factor for the development of severe PVR in serum and vitreous(P<0.05).CONCLUSION: With the aggravation of PVR, miR-126 expression in serum and vitreous decreased while miR-325 expression increased and correlated with TGF-β, TNF-α, VEGF, and PDGF.

Effects of different duration of exercise preconditioning on cerebral blood flow and microglia activation related proteins in rats with vascular dementia / 中国康复医学杂志

Objective:To explore the effects of different duration of exercise preconditioning on changes in cerebral blood flow and microglia activation related proteins in rats with vascular dementia. Method:Sixty SPF SD male rats were used to prepare vascular dementia rat models by permanent ligation of bilateral common carotid arteries.They were randomly divided into the model group,sham-operated group,ex-ercise preconditioning 4-week model group,exercise preconditioning 4-week sham-operated group,exercise pre-conditioning 2-week model group and exercise preconditioning 2-week sham-operated group,with 10 rats in each group.The exercise preconditioning 4-week rats received 30 minutes of moderate intensity non-weight-bear-ing swimming training 5 times a week for 4 weeks before modeling,while the exercise preconditioning 2-week rats received the same training for 2 weeks.Morris water maze was used to detect the spatial learning and memory ability of rats,laser speckle imaging technique was used to observe the changes of cerebral blood flow and the opening of collateral circulation of rats at different time point before and after the model-ing,and Western Blotting was used to detect the expression of TLR4 and Iba 1 protein in hippocampus. Result:Compared with the sham-operated group and the exercise preconditioning 2-week sham-operated group,the average escape latency time of rats in the exercise preconditioning 4-week sham-operated group,the model group,the exercise preconditioning 4-week model group and the exercise preconditioning 2-week model group was significantly prolonged(P＜0.05).Compared with the exercise preconditioning 4-week sham-operated group,the average escape latency time of rats in the model group and the exercise preconditioning 4-week model group was significantly prolonged(P＜0.05).Compared with the model group and exercise preconditioning 4-week model group,the average escape latency time of rats in exercise preconditioning 2-week model group was significantly decreased(P＜0.05).The simple effect of repetitive measurement deviation analysis suggested that the average cerebral blood flow before modeling,2h after modeling,3d after modeling and 7d after model-ing was statistically significant between the groups(P＜0.05).The simple effect of time factor on average cere-bral blood flow of the model group,the exercise preconditioning 4-week model group and the exercise precon-ditioning 2-week model group was statistically significant(P＜0.01).The opening of collateral circulation of rats in each group was observed.Compared with the model group,less reduction in microvessel diameter was ob-served in the exercise preconditioning 2-week model group(P＜0.05).Compared with the sham-operated group,the exercise preconditioning 4-week sham-operated group and the exercise preconditioning 2-week sham-operat-ed group,Ibal and TLR4 protein expressions in the model group were significantly increased(P＜0.01).Com-pared with the model group,Ibal and TLR4 protein expressions in the exercise preconditioning 2-week model group were decreased(P＜0.05). Conclusion:Moderate intensity exercise preconditioning for 2 weeks can improve the learning and memory abili-ty of vascular dementia rats,but exercise preconditioning for 4 weeks has no obvious effect on the improve-ment of learning and memory ability.The mechanism may be related to the improvement of cerebral blood flow status and the inhibition of microglia activation.

Advances in the application of laser speckle contrast imaging in animal models of chronic cerebral hypoperfusion / 中国比较医学杂志

A visual and quantitative method of dynamically measuring microcirculatory blood flow in a tissue or organ in real time was developed using laser speckle contrast imaging technology.It has been used in numerous microcirculation detection domains because of its benefits of in vivo detection,real-time imaging,and ease of operation.Most animal models of chronic cerebral hypoperfusion involve decreasing blood flow to the brain from bilateral common carotid arteries,which can lead to a protracted deficit in cerebral blood supply.By monitoring and analyzing cortical cerebral blood flow,collateral circulation opening,and neurovascular coupling responses,laser speckle contrast imaging technology assesses the efficacy of modeling and the therapeutic effect of interventions in animal models of chronic cerebral hypoperfusion.This article summarizes the benefits and drawbacks of laser speckle contrast imaging in an animal model of chronic cerebral hypoperfusion to promote novel approaches to clinical care and academic study.

16O/18O- exchange internal standard preparation enhancing reliability of bio-sample natural bioactive compounds absolute quantitation.

Natural bioactive compounds (NBCs) are regarded as candidates for many medical applications widely. Due to the complicated structure and biosynthesis source, only a few NBCs were supplied with commercial isotopic labeled standards. This shortage resulted in poor quantitation reliability in bio-samples for most NBCs, considering the remarkable matrix effects. NBCs metabolism and distribution studies would be restricted consequently. Those properties played critical roles in drug discovery and development. In this study, a fast, convenient, widely adopting 16O/18O exchange reaction was optimized for stable, available, affordable NBCs 18O-labeled standards preparation. With 18O- labeled internal standard, a UPLC-MRM-based NBCs pharmacokinetics analysis strategy was formed. Pharmacokinetics of caffeic acid with Hyssopus Cuspidatus Boriss extract (SXCF) dosed mice was carried out by established strategy. Compared with traditional external standards quantitation, adapting 18O-labeled internal standards, both accuracy and precision were enhanced significantly. Thus, the platform built by this work would accelerate the pharmaceutical research with NBCs, by providing a reliable, wide-adapted, affordable, isotopic internal standard-based bio-samples NBCs absolute quantitation strategy.

Miao medicinal crossbow acupuncture therapy as adjuvant treatment for lung cancer pain: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of Miao medicinal crossbow acupuncture therapy as adjuvant treatment for lung cancer pain based on oxycodone hydrochloride extended-release tablet.@*METHODS@#A total of 60 patients with lung cancer pain were randomized into an observation group (30 cases, 1 case dropped off) and a control group (30 cases). In the control group, oxycodone hydrochloride extended-release tablet was given orally, 10 mg a time, once every 12 hours. On the basis of the treatment in the control group, Miao medicinal crossbow acupuncture therapy was applied once every other day in the observation group. The treatment of 14 days was required in the two groups. Before and after treatment, the numerical rating scale (NRS) score, number of break-out pain and Karnofsky performance status (KPS) score were observed in the two groups. The equivalent oxycodone consumption and rate of adverse reactions were recorded, the analgesic effect was evaluated in the two groups.@*RESULTS@#Compared before treatment, the NRS scores and number of break-out pain were decreased while the KPS scores were increased after treatment in the two groups (P<0.01). After treatment, the NRS score and number of break-out pain in the observation group were lower than the control group (P<0.01), the KPS score in the observation group was higher than the control group (P<0.05). The equivalent oxycodone consumption of whole course and the rate of adverse reactions i.e. constipation, drowsiness, nausea and vomiting in the observation group were lower than the control group (P<0.05). The analgesic effect rate was 93.1% (27/29) in the observation group, which was superior to 63.3% (19/30) in the control group (P<0.05).@*CONCLUSION@#On the basis of oxycodone hydrochloride extended-release tablet, Miao medicinal crossbow acupuncture therapy as adjuvant treatment can effectively relieve the pain degree, reduce the number of break-out pain and improve the health status and quality of life in patients with lung cancer pain, enhance the efficacy of medication and reduce its adverse reactions.

Clinical features and microsurgical reconstruction of congenital unilateral absence of the vas deferens with obstructive azoospermia: a tertiary care center experience / 亚洲男科学杂志(英文版)

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.

Research progress of the diagnosis and treatment of anterior shoulder instability / 中国修复重建外科杂志

The shoulder joint is the most prone to dislocation in the whole body, and more than 95% of them are anterior dislocation. Improper treatment after the initial dislocation is easy to lead to recurrent anterior dislocation or anterior shoulder instability, and the outcomes following conservative treatment is poor. Anterior shoulder instability can damage the soft tissue structure and bone structure that maintain the stability of shoulder joint, among which bone structure is the most important factor affecting the stability of shoulder joint. Diagnosis should be combined with medical history, physical examination, and auxiliary examination. Currently, three-dimensional CT is the most commonly used auxiliary examination means. However, various bone defect measurement and preoperative evaluation methods based on three-dimensional CT and the glenoid track theory have their own advantages and disadvantages, and there is still a lack of gold standard. Currently, the mainstream treatment methods mainly include Bankart procedure, coracoid process transposition, glenoid reconstruction with free bone graft, Bankart combined with Remplissage procedure, and subscapular tendon binding tamponade, etc. Each of these procedures has its own advantages and disadvantages. For the diagnosis and treatment of anterior shoulder instability, there are still too many unknown, further research and exploration need to be studied.

Mid-term effectiveness of arthroscopic Bankart repair in treatment of recurrent anterior shoulder dislocation / 中国修复重建外科杂志

OBJECTIVE@#To investigate the mid-term effectiveness of arthroscopic Bankart repair for recurrent anterior shoulder dislocation.@*METHODS@#The clinical data of 107 patients with recurrent anterior shoulder dislocation who met the inclusion criteria between January 2017 and June 2021 was retrospectively analyzed, and all patients underwent arthroscopic Bankart repair. There were 88 males and 19 females. The age of the primary dislocation ranged from 13 to 48 years (mean, 23.3 years). The number of preoperative dislocations was 2-160 times (median, 7 times). The duration of preoperative instability was 0.2-240.0 months (median, 36.0 months). The mean age at operation was 28.2 years (range, 16-61 years). There were 43 cases of left shoulder and 64 cases of right shoulder. The proportion of glenoid defects in 63 patients was 1.7%-16.1% (mean, 8.1%). MRI showed that none of the patients had rotator cuff tears or shoulder stiffness. The CT three-dimensional reconstruction was performed at 1 day after operation to evaluate the distribution of implanted anchors and the occurrence of glenoid split fracture and whether there were nails pullout at the implant site. The postoperative complications were observed, and the pain and function of the shoulder were evaluated by visual analogue scale (VAS) score, Rowe score, Constant-Murley score, and American Shoulder and Elbow Surgeons (ASES) score. The recurrence of instability, the results of apprehension test, the number of patients who returned to preoperative sports level, and the satisfaction rate of patients were recorded.@*RESULTS@#All patients were successfully operated and were followed up 20-73 months (mean, 41.5 months). All incisions healed by first intention. The CT three-dimensional reconstruction at 1 day after operation showed that the anchors were located at the 2 : 00-5 : 30 positions of the glenoid, and there was no glenoid split fracture or nails pullout at the implant site. At last follow-up, VAS score was significantly lower than that before operation, and Rowe score, Constant-Murley score, and ASES score were significantly higher than those before operation ( P<0.05). Seven patients (6.5%) had recurrence of anterior shoulder dislocation at 23-55 months (mean, 39.9 months) after operation, including 6 cases of dislocation and 1 case of subluxation. At last follow-up, 51 patients (47.7%) returned to preoperative sports level, and 11 patients (10.3%) had a positive apprehension test. The patients' satisfaction rate was 90.7% (97/107). Among the 10 patients who were not satisfied with the surgical effectiveness, 7 patients had postoperative recurrence of instability, and 3 patients felt that they did not return to preoperative sports level.@*CONCLUSION@#Arthroscopic Bankart repair has good mid-term effectiveness in patients with recurrent anterior shoulder dislocations, minimal or no glenohumeral bone defects and low sports need.

Evaluation of clinical efficacy and safety on phacoemulsification combined with gonioscopy-assisted angle plasty for primary angle-closure glaucoma with cataract / 中华实验眼科杂志

Objective:To evaluate the efficacy and safety of phacoemulsification combined with gonioscopy-assisted angle plasty (Phaco-GAAP) for primary angle closure glaucoma (PACG) with cataract.Methods:A case series study was carried out.Twenty-five eyes of 22 patients with PACG and cataract were enrolled in Beijing Tongren Hospital from April 2022 to August 2022.All of the patients received Phaco-GAAP surgery.During the operation, viscoelastic-assisted goniosynechialysis was performed at first, followed by a secondary angle plasty for residual peripheral anterior synechiae (PAS) based on the quantified assessment by gonioscopy, and the extent of PAS was recorded intraoperatively.The operated eyes were followed at 1 day, 1 week, 1 month and 3 months after surgery to evaluate intraocular pressure (IOP), PAS range, the number of anti-glaucoma drugs application, operation-related complications, and success rate.The qualified success rate was defined as medicine-controlled IOP ≤21 mmHg after surgery, and complete success rate was defined as IOP ≤21 mmHg without any anti-glaucoma medication.This study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Beijing Tongren Hospital (TRECKY2021-136). Written informed consent was obtained from each patient prior to entering the research cohort.Results:The extent of PAS was [270(225, 360)°], [165(110, 215)°] and [100(35, 175)°] at preoperation, first and secondary angle plasty, respectively, showing a significant difference among them ( χ2 =40.742, P<0.001). The PAS range was significantly reduced at first angle plasty in comparison with preoperation and was significantly reduced at secondary angle plasty in comparison with at first angle plasty (both at P<0.001), and the proportion of the angle PAS range ≥180° decreased from 48% to 24% after second angle plasty.In 13 eyes finished gonioscopy, the PAS range was [240(195, 305)°], [60(25, 182.5)°], [170(120, 275)°]and [180(140, 280)°]at preoperation, at the end of operation, postoperative 1 month and 3 months, respectively, with a significant difference ( χ2 =23.631, P<0.001). The PAS range was significantly smaller at postoperative 1 month, 3 months than that at preoperation (both at P=0.004) and larger than that at the end of operation ( P=0.011, P=0.003). The IOP was (40.19±17.23), (15.80±7.98), (13.89±5.09), (12.80±3.79) and(13.24±2.78) mmHg before operation and 1 day, 1 week, 1 month and 3 months after operation, respectively, showing a significant difference ( F=44.031, P<0.001), and the IOP was significantly reduced after operation (all at P<0.001). The PAS range at the end of operation was positively correlated with preoperation ( rs=0.409, P=0.042). The complete and qualified success rates were 95.8%, 95.8% for postoperative 1 month, 95.8% and 100% for postoperative 3 months, respectively.The primary complication was intraoperative anterior chamber angle hemorrhage, with an incidence of 68%. Conclusions:Phaco-GAAP can intraoperatively quantify PAS range and guide secondary angle plasty, therefore, it is an effective and safe surgical intervention for PACG with cataract.

Apply ultra-thin lobulated anterolateral thigh perforator flap in repairing of large soft tissue defect in foot: a report of 8 cases / 中华显微外科杂志

Objective:Exploring the clinical efficacy of using ultra-thin lobulated anterolateral thigh perforator flap(ALTPF) with retrograde separation of perforating vessels from the superficial and deep junction layer of the superficial fascia to repair large soft tissue defects in the foot.Methods:From August 2021 to November 2022, 8 patients (5 males and 3 females) were admitted to the Second Department of Hand and Foot Surgery, the Affiliated Central Hospital of Dalian University of Technology. The patients were 28 to 52 years old in age. The soft tissue defects were located in dorsal and plantar foot. At the plantar foot, the wound involved the weight-bearing area with explosion of bone, tendon or internal fixtures. The area of soft tissue defects was 6.0 cm × 5.0 cm - 16.0 cm × 8.0 cm, and the sizes of ALTPF were 8.0 cm ×5.5 cm - 18.0 cm × 8.5 cm. Preoperative high frequency CUD combined with CTA angiography were employed to locate the 2 flap perforator vessels. By keeping the perforator vessels at center and according to the soft tissue defect area and the wound shape, an ALTPF with a proper size and shape was designed in anterolateral thigh. The perforator were separated in the boundary layer between superficial and deep fascia, where it helped to obviously thin the flap. After the flap was harvested, it was further lobulated between the 2 perforators into 2 lobes after having confirmed the effective blood supply. Finally the lobulated ALTPF was transferred to covered the defect in foot. Cautions should be taken to ensure that the flap covered the weight-bearing area of foot. All the donor sites were directly sutured. Postoperative follow-up was conducted to observe the survival of flaps and the functional recovery of the reconstructed site, also to evaluate the clinical effect. Postoperative follow-up included outpatient visits and reviews over WeChat or telephone. Recovery of the ankle motor function was evaluated according to the American Orthopedic Foot and Ankle Societ (AOFAS) ankle-hind foot score scale.Results:All 8 ALTPF survived. Over 6 to 18 months (10.8 months in average) of follow-up, the transferred flaps had good blood supply, soft in texture, with good elasticity and thin in appearance. Appearance and function of donor sites recovered well, except 1 patient who had mild scar hyperplasia. The plantar flap had good abrasion resistance. No flap damage, bleeding or granulation tissue hyperplasia occurred when walking. The mean score of AOFAS ankle-hind foot score achieved 95.6.Conclusion:The application of ultra-thin lobulated ALTPF with retrograde separation of perforating vessels from the superficial fascia at the junction layer for repairing large soft tissue defects in the foot has good clinical efficacy.

Primary retroperitoneal soft tissue sarcoma resection combined with nephrectomy: a report 27 cases / 中华普通外科杂志

Objective:To investigate the efficacy and safety of retroperitoneal soft tissue sarcoma resection combined with nephrectomy.Methods:The clinical data of 27 cases undergoing retroperitoneal soft tissue sarcoma resection combined with nephrectomy at the Gastrointestinal Tumor Center , Guangdong Provincial Hospital , Traditional Chinese Medicine from Jun 2017 to Aug 2022 were retrospectively analyzed for the indication of nephrectomy, postoperative progression of renal insufficiency and survival rate.Results:Twenty-six cases (96%) achieved R 0/R 1 resection and 1 case nderwent R 2 resection. Six cases underwent combined unilateral nephrectomy and 21 patients underwent combined multi-organ resection with a median number of resections of 4 (2,5). Postoperative pathology suggested that the combined resected kidney was positive for tumor infiltration in 17 cases. Five cases had Clavien-Dindo grade 3 or higher complications and no deaths occurred within 30 days after surgery. At the 90th day after surgery, 19 cases (70%) had decreased renal function ( Z=2.88, P=0.04), with a median decrease of -3.96 (-30.36, 0.31)ml·(min·1.73 m 2) -1, including 8 cases of preoperative Chronic Kidney Disease(CKD)1 stage progression (6 cases of CKD 2 stage, 2 cases of CKD 3 stage); 2 cases of CKD 2 stage progressed to CKD 3 stage; 1 case of preoperative CKD 3 stage progressed to CKD 4 stage. During the follow-up period of 3-38 months, no patient progressed to CKD 5 stage and no patient required dialysis treatment. Conclusion:Retroperitoneal soft tissue sarcoma resection combined with nephrectomy is safe and feasible while improving tumor radicality.

Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-κB in inflammatory response

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Low XIST expression in Sertoli cells of Klinefelter syndrome patients causes high susceptibility of these cells to an extra X chromosome / 亚洲男科学杂志(英文版)

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.

Modified bilateral carotid artery ligation to establish a vascular dementia rat model and investigate changes in cerebral blood flow and effects on angiogenesis-related proteins / 中国实验动物学报

Objective Apply modified bilateral carotid artery ligation to establish a VD rat model to observe changes in cerebral blood flow and expression of angiogenic proteins.Methods Thirty-six SD male rats were randomly divided into a sham group(n = 18)and model group(n = 18).In the sham group,only the bilateral carotid artery was isolated without ligation,whereas in the model group,the bilateral carotid artery was ligated to establish the VD model.The Morris water maze behavior test was applied before and 14 days after modeling.Variation in cerebral blood flow was detected by laser speckle contrast imaging.Protein expression of HIF-1α,VEGF,and HO-1 was detected by Western Blot.IL-4 and IL-10 contents were measured by ELISA.Results At 14 days after modeling,escape latency was significantly prolonged and the frequency of crossing the platform had significantly decreased in the model group compared with the sham group(P<0.05).At 2 hours,3 days,and 7 days after modeling,cerebral blood flow in the model group was significantly lower than that in the sham group(P<0.05).At 14 and 21 days after modeling,no significant difference was found in cerebral blood flow between sham and model groups(P>0.05).In the model group,cerebral blood flow was decreased to a minimum at 2 hours after modeling(P<0.05)and then began to recover.The peak of recovery occurred at 3～7 days after modeling and returned to the level before modeling on day 14 after modeling.At postoperative day 21,expression of HIF-1α,VEGF,and HO-1 proteins in the hippocampus of the model group was increased remarkably(P<0.05)and the serum contents of IL-4 and IL-10 in the model group were significantly increased compared with those in the sham group(P<0.05).Conclusions The variation in cerebral blood flow in the VD rat model established by the modified bilateral carotid artery ligation was dependent on time.At postoperative day 21,HIF-1α,VEGF,and HO-1 in the hippocampus were increased significantly,which was accompanied by increased levels of IL-4 and IL-10.

Applications of QSAR in Toxicological Risk Assessment of Medical Devices / 中国医疗器械杂志

The chemical characterization analysis of a medical device often results in chemical substances with unknown toxicities. While identification of each individual toxicity could result in a time-consuming hurdle with tremendous labor and financial burden, quantitative structure-activity relationship (QSAR) is of great significance for toxicity risk assessment of such chemical substances. By establishing quantitative relationship between the molecular structures or active groups of similar chemical compounds with their biological activities, QSAR can be utilized to predict the toxicity of such target compounds with significantly reduced cost and time. In this article, the authors generally summarized the mechanisms of QSAR approaches, current applications of QSAR modeling in the field of medical device, an introduction of the characteristics of publicly and commercially-available QSAR software, and briefly explored future trends of QSAR modeling in medical device toxicological risk assessment. The utilization of QSAR would undoubtedly further advance the toxicological risk assessment of medical devices.

Autophagy enhanced by curcumin ameliorates inflammation in atherogenesis via the TFEB-P300-BRD4 axis

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

Clinical expert consensus on platelet-rich plasma treatment for lateral epicondylitis (2022 version) / 中华创伤杂志

Lateral epicondylitis is a common clinical disease with characteristics of lateral elbow pain, insidious onset and easy recurrence, which can cause forearm pain and decreased wrist strength, seriously affecting patients′ daily life and work. Although there are various treatment methods for lateral epicondylitis with different effects, standard treatments are still lacking nowadays. Platelet-rich plasma (PRP) has good effects on bone and tendon repair, and is now widely used in the treatment of lateral epicondylitis. However, there is a lack of a unified understanding of the technology and specifications of PRP in the treatment of lateral epicondylitis. Therefore, the Sports Medicine Branch of the Chinese Medical Association and Physical Medicine and Rehabilitation Branch of the Chinese Medical Association organized experts in the fields of sports medicine and rehabilitation medicine in China to formulate the "clinical expert consensus on platelet-rich plasma treatment for lateral epicondylitis (2022 version)", and proposed suggestions based on evidence-based medicine mainly from the concept, epidemiology and pathophysiology of lateral epicondylitis, symptoms, signs and imaging manifestations of lateral epicondylitis, PRP concept and application component requirements, quality control of PRP preparation technology, indications and contraindications of PRP in the treatment of lateral epicondylitis, PRP injection in the treatment of lateral epicondylitis, application of PRP in the operation of lateral epicondylitis, related problems after PRP treatment of lateral epicondylitis, evaluation of the results after PRP treatment of lateral epicondylitis, and health and economic evaluation of PRP treatment of lateral epicondylitis, so as to provide guidance for clinical diagnosis and treatment.