Objective:To investigate the clinical phenotype and genetic characteristics of a family with mitochondrial DNA depletion syndrome (MTDPS8B) caused by RRM2B gene mutation. Methods:Data of a family with MTDPS8B admitted to Department of Pediatric Neurology, Linyi People's Hospital in November 2019 were collected. Whole exome sequencing, mitochondrial loop gene sequencing and Sanger sequencing were used for genetic test in the child and family members, and pathogenicity analysis and protein 3D modeling on the mutation sites were conducted. The clinical phenotype and genetic characteristics of the family members were summarized.Results:Six subjects in these 8 individuals from the three generations of this family underwent genetic test. Four subjects had c.627G>A(p.M209I) (NM_001172477) heterozygous variation in RRM2B gene on the chromosome 8, and the variation was highly conserved; and no report on this variation has been found in domestic and foreign databases yet. Protein 3D modeling found that this variation may affect protein stability and function. The proband (male) and two older sisters carried the same variant had MTDPS8B, manifested as gastrointestinal dysfunction and progressive decline in motor function and intelligence, while the mother carried the same variant only had intellectual disability; the father and eldest sister did not carry the mutation and had normal clinical phenotype; the maternal grandparents had normal clinical phenotype and had passed away without genetic test; variation and disease were isolated in this family. The variation was interpreted as pathogenic (PM1+PM2+PP1+PP3) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. Conclusion:The c.627G>A variant can cause RRM2B gene-related disease, and family members carried the same variants vary in clinical severity.

Objective To explore the efficacy and safety of different antiplatelet drugs combined with rivaroxaban in patients with lower extremity arteriosclerosis obliterans.Methods The clinical data of patients with lower extremity arteriosclerosis obliterans who were symptomatic and underwent surgical treatment at the Vascular Surgery Department of Nanjing Drum Tower Hospital from January 2018 to December 2021 were retrospectively analyzed.According to the different antiplatelet medications taken by patients,patients were categorized into aspirin group,clopidogrel group and cilostazol group.Baseline data of patients were collected,and patients were followed up and the incidence of major adverse cardiovascular events,major adverse limb events,major bleeding and clinically related non-major bleeding events were compared in different groups.Results A total of 632 patients were included in the study.There was no significant difference in the incidence of major adverse cardiovascular events,major adverse limb events,major bleeding and clinically related non-major bleeding events after the baseline data was balanced by inverse probability of treatment weighting.The results of subgroup analysis were generally consistent with those of the overall study.Conclusion The combination of clopidogrel or cilostazol with rivaroxaban may serve as a novel option for dual antithrombotic therapy in patients diagnosed with lower extremity arteriosclerotic obliterans.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Restless legs syndrome (RLS) is a common sensorimotor disorder. Although it does not pose a threat to life, it seriously affects the quality of life of patients. RLS pathogenesis is still unclear, and its incidence is associated with a variety of risk factors, including genetic factors and non-genetic factors. Genetic factors involve more than 20 risk genes, such as meis homeobox 1 ( MEIS1), BTB domain containing 9 ( BTBD9), mitogen-activated protein kinase kinase 5 ( MAP2K5), and protein tyrosine phosphatase receptor type Db ( PTPRD). Non-genetic factors include regional age, gender, obesity, medical related diseases, neuropsychiatric diseases and drugs. This paper reviews the recent advance in risk factors and related pathogenesis of RLS to provide references for early prevention and treatment of the disease.

Objective:To construct a predictive model for the risk of major adverse cardiovascular events(MACE) after surgery in patients with symptomatic arteriosclerosis obliterans(ASO) .Methods:From Jan 2018 to Dec 2021, 957 patients with symptomatic ASO admitted to Nanjing Drum Tower Hospital were selected and divided into MACE and non-MACE groups according to whether they had a post-op MACE. A risk prediction model was constructed based on a stepwise regression method with multi-factor COX regression analysis. The model was evaluated using the receiver operating characteristic curve (ROC), the calibration curve to assess the model fit, and the Bootstrap method for internal validation.Results:MACE occurred in 143 patients (14.94%). After COX regression analysis, BMI, creatinine clearance, fibrinogen, rivaroxaban and previous history of surgery were enrolled into model constructing. The ROC curve assessed the model with a C-statistic of 0.690 (95% CI: 0.644-0.736), sensitivity and specificity of 49.2% and 80.7% respectively, a Jorden index of 0.299 and an optimal cut-off value of 0.086. Calibration curves showing agreement between predicted and actual observed values. Internally validated C-statistic of 0.689 (95% CI: 0.672-0.700). The population was divided into high and low risk groups based on the best cut-off value and analysed for survival. The difference between the two groups was statistically different. Conclusion:The risk prediction model for the occurrence of MACE based on clinical parameters is simple and convenient, with good predictability and good discriminatory ability, and can provide reference for the assessment and treatment of MACE in ASO patients.

Clinical research is usually aimed at and guided by therapeutic efficacy. Clarifying the placebo effect and the nocebo effect from treatment outcomes is an important issue in clinical research. This paper reviews the meaning of the placebo effect， suggesting that factors that may produce the placebo effect in clinical practice include past experience associations， patient expectations， suggestion， and doctor-patient relationships. It also summarizes the characteristics of the nocebo effect， its influencing factors， and its impact on clinical prognosis. Combining the characteristics of traditional Chinese medicine， this paper explores the design of acupuncture clinical trials that can reflect the measurement of the placebo effect， attempting to provide a clearer interpretation of the placebo effect in the evaluation of acupuncture efficacy in traditional Chinese medicine. Taking primary insomnia as an example， a prospective randomized placebo-controlled trial is designed to observe and evaluate the relationship between the treatment effects of acupuncture and the placebo effect in different patients under the treatment of the same doctor. Group comparisons will help better distinguish clinical effects in different situations. The authors also attempt to explore the responsive population to the placebo effect and the effects of placebos in different populations.

OBJECTIVE To study th e pharmacodynamics and pha rmacokinetics of Qinglian ningxin capsule in rats with ischemic arrhythmia. METHODS Totally 30 male SD rats were randomly divided into blank control group ，model control group ， Qinglian ningxin capsule group （4.00 g/kg），Artemisia annua group（1.43 g/kg），Coptis chinensis group（0.42 g/kg），with 6 rats in each group. Administration groups were given relevant medicine intragastrically ；model control group and blank control group were given normal saline intragastrically ，once a day ，for consecutive 7 days. After last medication ，except for blank control group，other groups were given Posterior pituitary injection via tail vein （1 u/kg） to induce ischemic arrhythmia model. electrocardiogram changes of rats in each group were recorded. Another 36 rats were randomly divided into Qinglian ningxin capsule model group and Qinglian ningxin capsule control group （4.00 g/kg），A. annua model group and A. annua control group （1.43 g/kg），C. chinensis model group and C. chinensis control group （0.42 g/kg）. After the rats in each model group were injected with Posterior pituitary injection （1 u/kg）via tail vein ，administration groups were given relevant drugs intragastrically ， and control groups were given constant volume of normal saline intragastrically. Blood was taken from the orbit at different time points（0，0.25，0.75，1，2，4，6，8，12 and 24 h）. The concentrations of berberine hydrochloride and artemisinin in plasma were determined by HPLC ，and the pharmacokinetic parameters were calculated by WinNonlin 7.0 software. RESULTS Compared with the model control groups ，Qinglian ningxin capsule could significantly improve the heart rate slowing of rats and redu ced the prolongation of PR interval and QT interval significantly ，and the effects were generally better than those of A. annua group and C. chinensis group（P＜0.05）. Compared with A. annua control group and C. chinensis control group ，cmax，AUC0－t and AUC 0－∞ of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule control group，while CL was decreased significantly ；t1/2z of artemisinin was prolonged significantly （P＜0.05）. Compared with Qinglian ningxin capsule control group ，cmax（except artemisinin ），AUC0－t，AUC0－∞，MRT0－t and MRT 0－∞（except artemisinin ）of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule model group ，while CL was decreased significantly（P＜0.05）. CONCLUSIONS Qinglian ningxin capsule could significantly improve ischemic arrhythmia better than A. annua and C. chinensis ，and can improve the absorption of berberine hydrochloride and artemisinin in model rats and slow down their elimination.

Objective:To evaluate the clinical effect of fibula flap in the repair of large segment of composite tissue defect in upper limb.Methods:From April, 2015 to June, 2019, 7 patients with large composite tissue defects in upper limbs were treated. All of them with various skin, vessel, nerve, tendon and other tissue defects. Repairing was well planned before surgery according to the type, location and size of defect. While in repairing of the bone and skin defect, fibula flap was taken from the shank and to repair the defects of nerve, tendon and vessels in upper limb. Regular followed-ups were made after surgery.Results:The 7 fibula flaps all survived. Postoperative follow-up ranged between 8 to 36 (averaged of 15) months. All the reconstructed limbs were in satisfactory appearance and function recovery. All the patients were able to manage their daily activities and live independently. The shape and function of donor sites were good. According to the Enneking system, the outcomes were graded as excellent in 4 cases and good in 3, with the average score was 25.9 points.Conclusion:Free grafting of vascularised fibula flap is especially feasible to be used in the repair of large bone tissue defect of upper limb. It repairs the defects of skin, vessel, nerve and tendon with the flap from a single donor site.

Background: Granular cell tumor (GCT) is an uncommon tumor, and gastrointestinal tract GCT is even more rare. Aims: To investigate the clinicopathological characteristics, treatment and prognosis of gastrointestinal tract GCT. Methods: Nine cases of gastrointestinal tract GCT from January 2017 to June 2021 at the 903rd Hospital of Joint Logistics Support Force, PLA and Jinhua Municipal Central Hospital Medical Group were retrieved. The clinical data, histopathological characteristics, treatment, and prognosis were retrospectively analyzed. Results: In the 9 patients with gastrointestinal tract GCT, ratio of male to female was 2:1, age at diagnosis was 19-60 years, with a median age of 52 years. Six GCT were found in esophagus, 2 in colorectum and 1 in anus. Endoscopic results showed submucosal protrusion or sessile polyps ranging in size from 2-12 mm with a median of 5 mm. Histology results showed that tumors were located in mucosa and/or submucosa, arranged in solid sheets or nests, with an infiltrative margin and inflammatory infiltrates. Tumor cells were mainly plump and polygonal with abundant cytoplasm and eosinophilic granules. Nuclei were small, the nuclear-cytoplasmic ratio was very low. Mitotic figure was rare. Immunohistochemistry results showed that S100 and CD68 proteins were positive in all patients, SOX10, CD56, Calretinin and Syn were positive in some patients, and CKp, Desmin, SMA, CD117, CD34, Dog1, and α-inhibin were negative in all patients. Esophageal and colorectal GCT patients received endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). The anal GCT patient underwent local resection. Recurrence or metastasis were not observed during 9-53 months of follow-up. Conclusions: Gastrointestinal tract GCT is rare with non-specific clinical symptoms and submucosal protrusion or sessile polyps under endoscopy. Gastrointestinal tract GCT has special pathomorphology and immunophenotype. EMR or ESD is recommended for small and superficial lesions. Long-term follow-up should be performed.

【Objective】 To identify one blood sample with ambiguous antibody screening result, explore the identification strategy of complex antibodies and provide blood transfusion plan. 【Methods】 Blood typing and antibody screening were performed by serological test. The genotyping of Diego blood group was carried out by gene detection. Absorption and elution test were designed to identify the complex antibodies. 【Results】 Serological test showed that the patient′s blood type was B, ccDEE, Jk(a-b+ ), Le(a-b+ ), Fy(a+ b-), Di(a+ b-). The results of genotyping showed that the Diego genotype of the patient was Di (a+ b-). Based on the above results, absorption and elution tests were designed and IgG anti-Di^b, IgG anti-Ce, and IgG anti-Jk^a antibodies were detected in serum of the patient. Combined with the use of immunoglobulin and targeted blood transfusion measures, successful treatment was provided for the patient. 【Conclusion】 For the identification of antibodies against high frequency antigen combined with multiple antibodies, a variety of experimental techniques and methods should be combined, and the experimental scheme should be designed flexibly.