Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

Objective To evaluate the medium-to-long-term efficacy of parallel stenting technology in treating aortoiliac occlusive disease(AIOD).Methods The clinical data of 18 patients with symptomatic AIOD,who received parallel stenting(using metal bare stent or covered stent)to reconstruct the aortoiliac artery at the Affiliated Hospital of Southwest Medical University of China from March 2017 to May 2019,were retrospectively analyzed.The patients included 14 males and 4 females with a mean age of(64.78±9.04)years.The surgical details,clinical success,complications,and stent patency rate were recorded.Results Both technical success and clinical success were achieved in all patients.A total of 62 stents were implanted,including 52 bare metal stents,9 covered stents and one renal artery balloon dilatation stent.After stent implantation,one patient each developed lacunar cerebral infarction,brachial artery pseudoaneurysm,decreased hemoglobin level,and thrombus migration into the renal artery,and after active management the patients were well discharged.The incidence of complications was 22％(4/18).During the follow-up period,3 patients developed in-stent restenosis,and the vascular lumen returned to patency after a second time of endovascular intervention.The postoperative 12-,18-,24-,30-,and 36-month main patency rates were 100％,95％,90％,85％,and 85％,respectively.Conclusion For the treatment of AIOD,parallel stenting technology has obtained satisfactory 3-year results.For the patients with complicated AIOD,this technique also carries a high technical success rate and an acceptable medium-to-long-term patency rate.

Objective To explore the effect and possible mechanism of petroleum ether extract from Gastrodia elata on A amyloid β-protein deposition in Caenorhabditis elegans(C.elegans).Methods C.elegans was used as the model organism,and the experiment was divided into blank group(Control group),GEPEE 0.5 mg·mL-1 group and GEPEE 1 mg·mL-1 group.The effects of GEPEE on paralysis,life span,oxidative stress,heat stress,reactive oxygen species(ROS)level and Aβ aggregation of C.elegans were investigated,qRT-PCR was used to detect the changes of gene expression related to insulin/IGF-1 signaling pathway(IIS)in C.elegans.The main components were analyzed by high performance liquid chromatography(HPLC).Results Compared with Control group,GEPEE could significantly improve the paralysis phenotype of C.elegans(P<0.01),prolong the lifespan of C.elegans(P<0.01),enhance the motility of C.elegans(P<0.01),and increased the resistance to external oxidative stress(P<0.01),the stress ability of high temperature(P<0.01),improved the deposition of Aβ in vivo(P<0.01),decreased the ROS content in C.elegans(P<0.01),decreased the expression levels of Aβ and DAF-2(P<0.01),increased the expression levels of DAF-16 and its target genes SOD-3,GSH-Px,HSF-1 and its target gene HSP-16.2,SKN-1 and its target gene GST-4(P<0.01).Its main components were p-hydroxybenzyl alcohol and p-ethoxylbenzyl alcohol by HPLC.This study showed that GEPEE can reduce Aβ-induced toxicity in CL4176 C.elegans by reducing ROS level in vivo,increasing antioxidant level and regulating IIS pathway.Conclusion GEPEE can inhibit the toxicity of Aβ protein,and its mechanism is related to the regulation of IIS signaling pathway.

Objective:To provide insight into the diagnosis for clinicians, the clinical characteristics, diagnosis and treatment history of 3 patients with 21-hydroxylase deficiency (21-OHD) and testicular adrenal rest tumors (TART) were analyzed.Methods:The clinical, laboratory and imaging data of 3 male patients with 21-OHD and TART, confirmed with CYP21 gene sequencing, from May 2010 to May 2021 in the First Medical Center of Chinese PLA General Hospital were analyzed retrospectively. The treatment strategy and clinical outcome were followed up.Results:All the 3 patients were first diagnosed with bilateral adrenal mass at the age of 27-42 years old. They were 145-162 cm tall. The levels of progesterone, 17-hydroxyprogesterone, and adrenocorticotropic hormone (ACTH) of the 3 patients were relatively high, and that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) of the 3 patients were low. Testosterone level of 1 patient was significantly elevated, and that of the other 2 patients was below the lower limit of normal range. Testicular ultrasound showed heterogeneous hyperechoic masses in both testes. CT of the adrenal glands showed bilateral adrenal enlargement with mass. All 3 patients were treated with dexamethasone. After 4-96 months of follow-up, 17-hydroxyprogesterone level was kept above the median normal level. One of the patients got married and had a baby after treatment. The sizes of adrenal hyperplasia and testicular masses reduced to various degrees with the change of the testicular masses being proportional to that of adrenal hyperplasia.Conclusions:Patients with 21-OHD are prone to have TART, leading to the impaired testicular function. Early glucocorticold therapy is beneficial to the reduction of TART and restoration of testicular function.

OBJECTIVE: Discuss the working ideas of the dynamic adjustment mechanism of medical device classification in the United States, and provide reference for the construction of medical device related mechanisms in China. METHODS: Collect and interpret the documents of regulatory background, procedures and orders of the dynamic adjustment mechanism of the medical device classification in the United States, and summarize the overall situation and specific cases of the medical device classification adjustment under this mechanism in recent years. RESULTS: The US work idea of the medical device classification dynamic adjustment mechanism is based on the latest valid scientific evidence, conducting risk analysis and identification, and determining the corresponding measures. CONCLUSIONS During the adjustment process, industry stakeholders have repeatedly discussed and achieved final agreement. Its procedures and working ideas can be used as a reference for China's work.
China ; United States ; United States Food and Drug Administration

Objective:To report our experience in treatment of patients with orthopaedic trauma during COVID-19 epidemic.Methods:We retrospectively analyzed the 67 patients with orthopedic trauma who had been treated at Department of Orthopaedics, Peking Union Medical College Hospital from February 1 to March 31, 2020. After screening for COVID-19 infection was performed under strict protection, the patients were diagnosed and assigned to outpatient emergency treatment or hospitalization according to their specific condition. Twenty-six patients were treated at the outpatient emergency department. They were 8 males and 18 females with an average age of 69.5 years. Of them, 6 with vertebral compression fracture were placed on bed brakes, 14 with limb fracture immobilized after close reduction, 2 with skin laceration treated with debridement and suture, and 4 with hip fracture immobilized in bed. In the 41 hospitalized patients, there were 14 males and 27 females with an average age of 68.5 years. In them, hemiarthroplasty was performed for 7 femoral neck fractures, kyphoplasty for 5 vertebral compression fractures, total elbow arthroplasty for one humeral intercondylar fracture, exploration and suture for one case of Achilles tendon rupture, and internal fixation surgery for the remaining 27 cases.Results:Most of the patients had osteoporotic fractures which accounted for 61.5% (16/26) of the outpatients and 68.3% (28/41) of the inpatients, respectively. The duration from injury to surgery averaged 2.3 days and the length of hospitalization 4.5 days for the 41 hospitalized patients, decreased compared with the corresponding data (3.1 days and 11.5 days) for the similar inpatients in the same period last year. In the 41 inpatients, fever was observed upon hospitalization in 4 cases and after operation in 26 cases, and related to their primary injury or surgical trauma in all. Acute pulmonary embolism happened during operation in one patient with femoral shaft fracture.Conclusions:The prevention and control of COVID-19 should be continued. The awareness and behavior of health care providers are expected to be enhanced by strict screening protocol, protection and supervision. The proportion of elderly patients with osteoporotic fracture increased during the COVID-19 pandemic. Shortage of blood was the major problem affecting the treatment. Timely surgical treatment should be indicated for the patients with orthopedic trauma, especially those with lower extremity fracture.

Objective: To explore the clinical features, diagnosis and prognosis of renal transplant recipients with NCP. Method: The clinical data of 2 cases of kidney transplant recipients with NCP were retrospectively analyzed. Based onclinical manifestations, blood routine, inflammatory factors, cell immunity, chest CT andtherapeutic effects, the diagnosis and treatment of NCP in kidney transplant recipients (5th edition) were compared to that ofordinary NCP patients. Both recipients developed onset of low andmoderate fever, with no cough or fatigue at the initial stage. Blood routine indicated a normal range of leukocytes,buta significant decrease in lymphocyte counts, increased C-reactive protein (CRP) , and slightly higher procalcitonin (PCT) . The cellular immunity was extremely low, and the chest CT showed multiple patchy ground glass shadows in both lungs. Result: After 1 week of onset, both patients had significant disease progression. The pathogenesis and imaging changes were highly similar tothatreported in ordinary NCP patients.Two patients were givensymptomatic supportive treatment by antiviral agents, stop uses ofimmunosuppression agents, small amount of hormone maintenance, intravenous drip of gamma globulin andrespiratory support toavoid secondary infections. At present, the condition of both patients is obviously improved, and renal function is stable. One of them has recovered and was discharged. Conclusion The clinical manifestations of NCP in renal transplant recipients were generally consistent with that of ordinary NCP patients. Although there is no established method for the treatment of NCP, it is effective by stopping uses of immunosuppressive agents, maintaining small and medium doses of hormones, actively restoring immunity, and providing respiratory support in a timely manner.

Objective:To explore the clinical features, diagnosis and prognosis of renal transplant recipients with COVID-19.Methods:The clinical data were retrospectively analyzed for 2 kidney transplant recipients with COVID-19. Based upon clinical manifestations, blood routine, inflammatory factors, cell immunity, chest computed tomography(CT)and therapeutic efficacies, the diagnosis and treatment of COVID-19 in kidney transplant recipients(Interim Edition V)were compared to that of ordinary COVID-19 patients. Both recipients had an onset of low/moderate fever. There was no initial symptom of cough or fatigue. Blood routine indicated a normal count of leukocytes, a marked lymphocytopenia, elevated C-reactive protein(CRP)and slightly higher procalcitonin(PCT). Cellular immunity was extremely low and chest CT showed multiple patchy ground-glass opacities in both lungs.Results:After 1 week of onset, both patients had a marked disease progression. The pathogenesis and imaging changes were highly similar to those reported for ordinary COVID-19 patients. For preventing secondary infections, both received symptomatic supportive measures of antiviral agents, withdrawing immunosuppressants, tapering of hormone maintenance dose, intravenous drip of gamma globulin and respiratory supports. Currently the conditions of both patients obviously improved and renal function was stable. One case recovered and was discharged.Conclusions:The clinical manifestations of COVID-19 in renal transplant recipients are generally consistent with that of ordinary COVID-19 patients. Although there is no established treatment for COVID-19, withdrawing immunosuppressants, maintaining small and medium doses of hormones, actively restoring immunity and providing respiratory supports in a timely manner are effective.

Immunological checkpoint inhibitors of anti-programmed cell death-1 and programmed cell death ligand-1(PD-L1)have already demonstrated remarkable clinical efficacy for solid tumors,however,the effectiveness of single drug therapy in immunotherapy is not very high. Therefore,exploring the appropriate therapeutic predictive biomarkers so as to accurately identify the potential patients suitable for this therapy has become a research hotspot. Studies have shown that biomarkers such as PD-L1,tumor mutation burden and mismatch repair deficiency may be related to the efficacy of immunotherapy. In-depth analysis and exploration of these markers may provide a basis for determining those patients who are more likely to benefit from check-point inhibitor.

Objective To evaluate the change of clinicopathological features and prognosis of papillary thyroid cancer over a 15-year period.Methods The clinicopathological features and outcomes of papillary thyroid cancer patients were analyzed in three groups according to the time of diagnosis:group Ⅰ (1997-2001),group Ⅱ (2002-2006),and group Ⅲ (2007-2011).Results As time advanced,the average age of papillary thyroid cancer patients increased,tumor stage,like size,extrathyroid invasion and lymph node metastasis decreased dramatically (P ＜ 0.01).The percentage of multifocality and bilaterality increased.The long-term follow up data (median follow up time was 6.6 years),indicated that the 15-year over all survival was 97.8％ and the 15-year disease-free survival was 90.2％.Tumor ≥3 cm,bilaterality,extrathyroid invasion,lymph node metastasis and AJCC stage were correlated with tumor recurrence.By multivariate COX-regression analysis only lymph node metastasis and bilaterality were independent risk factors.Conclusion The clinicopathological features of papillary thyroid cancer changed over 15 years,with the percentage of early-staged patients increased.Lymph node metastasis and bilaterality are two risk factors for tumor recurrence.