OBJECTIVE:To understand the present situation of ADR reporting entities in Shaanxi and Sichuan province,and provide evidence for the improvement of ADR monitoring. METHODS:Getting the overview of ADR monitoring at home and abroad by reading a lot of literature,the ADR monitoring entities(drug manufacturers,drug distributors and medical institutions) in Shaanxi and Sichuan province were selected as subject for cluster sampling,questionnaires were sent out and descriptive statis-tics analysis was adopted to processing and analyze the results. RESULTS:Totally 198 questionnaires were received,100 for Shaanxi province and 98 for Sichuan province. In Shaanxi and Sichuan province,there are 61 and 63 investigated subjects had es-tablished ADR monitoring departments,98.0% and 100% had had personnel for the ADR work;ADR monitoring work mostly be-longed to the quality control department in drug manufacturers and drug distributors,and belonged to pharmacy department in medi-cal institutions;most of them were equipped with computer,printer and other basic office equipment;however,the major duty of most was not clearly;13 and 23 subjects had special budget for ADR monitoring;87 and 89 subjects had communication with lo-cal ADR monitoring center,however,the information feedback was not very ideal;training the workers accounted for 80.0% and 83.0%,respectively;in terms of system construction,the standard operation procedure was relatively good,and the other related was not ideal;reporting quickly when finding ADR was 89.0% and 96.9%,88.0% and 96.9% of which had backup records for ADR reporting,it was mainly network report;Shaanxi province was better than Sichuan province about the satisfaction evaluation of ADR work. CONCLUSIONS:According to the results,it is suggested to adjust the structure of workers,buy related software re-source,improve the responsibilities and strengthen the financial support to promote the implementation of ADR monitoring.

OBJECTIVE:To investigate the situation of ADR reporting entities in Henan province and Hebei province to pro-vide reference for the improvement of ADR monitoring. METHODS:Literatures were consulted to investigate the ADR monitoring at home and abroad. With the subject of ADR reporting entities(pharmaceutical manufacturers,drug distributors and medical insti-tutions)in Henan and Hebei province,questionnaires and descriptive statistical analysis were conducted to analyze the results. RE-SULTS:186 valid questionnaires were received. There were respectively 58 and 62 ADR reporting entities with ADR monitoring de-partment in Henan and Hebei province,all of them had personnel who were responsible for ADR;ADR monitoring mostly belonged to quality control department in pharmaceutical manufacturers and drug distributors,and pharmacy department in medical institu-tions;most were equipped with computer,printer,phone and other basic office equipments;most were not clearly for major duty;there were respectively 24 and 2 entities with special budget for ADR monitoring;95.7% and 96.8% had communication with the local ADR monitoring centers,however,the information feedback was not ideal;86.7%and 98.9%had training for the stuff;stan-dard operation procedure was relatively good in Hebei province;96.7% and 98.9% would report ADR immediately after finding ADR,92.3% and 97.8% would record and backup the reported ADR;the form mainly by network report;the average degree of satisfaction evaluation in Henan province was higher than Hebei. CONCLUSIONS:According to the results,it is suggested to pro-mote the implementation of ADR monitoring by optimizing the work conditions,ensuring work fund and strengthening work feed-back.

OBJECTIVE:To investigate the present situation of adverse drug reaction(ADR)reporting entities in Jiangsu prov-ince and Guangdong province,and provide reference for the improvement of ADR monitoring. METHODS:With the overview of ADR monitoring at home and abroad by reading literatures,the ADR reporting entities(drug manufacturers,drug distributors and medical institutions) in Jiangsu province and Guangdong province were selected as objects for cluster sampling by questionnaires, and descriptive statistical analysis and other methods were adopted to process and analyze the results. RESULTS:There were totally 205 effective questionnaires. In Jiangsu province and Guangdong province,67 and 60 of the surveyed ADR reporting entities had specialized ADR monitoring departments,98.1% and 99.0% had equipped with specialized personnel for ADR work;ADR moni-toring mostly belonged to quality management department in drug manufacturers and distributors,and pharmacy department in medi-cal institutions;most entities were equipped with computers,printers,copiers and other basic office equipments;but most entities’ responsibilities were not clear enough;27 and 15 entities had specialized budget for ADR monitoring;97.2% and 96.9% had com-munication with ADR ,monitoring center,but the feedback information was unsatisfactory;85.0% and 86.7% had related training for personnel;establishing standard operating procedures of the system construction was relatively good,the other related system construction was still not ideal;91.6% and 90.8% would report ADR immediately after discovery,92.5% and 97.9% would back-up recording the ADR,mainly by internet reporting;the average scores in terms of job satisfaction in Jiangsu province were higher than Guangdong province. CONCLUSIONS:According to the results,it is suggested to improve the system construction of ADR monitoring,optimize working conditions,ensure financial support of ADR monitoring,and strengthen work communication and system construction and other measures to promote conduct of ADR monitoring.

Objective To study the surgical techniques and the clinical curative ettect of the reconstruction of adjacent large finger pulps with the modified sensate free proximal ulnar artery perforator flap.Methods From February,2013 to May,2016,20 fingers in 10 patients with adjacent large finger pulp defects crossing the DIP joint were reconstructed by the modified senate free proximal ulnar artery perforator flap.All the pulps of every patient were recovered by 1 flap in the first stage and the artificial syndactyly of two digits was divided in 7 weeks after the flap transfer in the second stage.In order to reconstruct the sensation of two pulps in each patient,firstly both of the proximal and distal ends of the cutaneous nerve in flaps were dissected and anastomosed with the most lateral and medial palmar digital nerves of two adjacent fingers respectively,which were divided into 2 groups.Secondly the cutaneous nerve in the middle part of flap was cut and the two ends were anastomosed with the other two palmar digital nerves in the second surgery.There were 8 fingers in 4 patients with the index and middle finger pulp defects,12 fingers in 6 patients with the middle and ring finger defects.The flap size was from 5.0 cm×3.5 cm to 5.5 cm×4.0 cm,and the perforator artery was anastomosed with the palmar digital artery in 6 cases and with the joint branch of digital artery in 4 cases.Results Nine flaps survived uneventfully except the venous congestion was found in 1 flap which was salvaged successfully by acupuncture bleeding.Also,no congestion or ischemia of all the 20 pulp flaps occurred right after releasing the artificial syndactyly.The time of followed-up was from 11 months to 32 months with the average of 17 months after the second surgery.The static two point discrimination of the 2 groups of the sensate pulp flap was (7.3 ± 1.2) mm and (8.6 ±2.4) mm respectively.There was no significant difference between groups (P ＞ 0.05).These 20 pulp flaps were also assessed by the Semmes-Weinstein monofilament test with the result of diminished light touch in 14 pulps and diminished protective touch in 6 pulps.The total active motion in all 20 fingers was (248.0±4.5) °.No patients suffered cold intolerance and local pain but 1 had hypersensitiveness in the pulp flap.Conclusion The modified sensate free proximal ulnar arte~ perforator flap is a practical alternative for the reconstruction of two large adjacent pulps with satisfactory functional and aesthetic outcomes.

Microsatellite instability (MSI) is a key biomarker for cancer therapy and prognosis. Tra-ditional experimental assays are laborious and time-consuming, and next-generation sequencing-based computational methods do not work on leukemia samples, paraffin-embedded samples, or patient-derived xenografts/organoids, due to the requirement of matched normal samples. Herein, we developed MSIsensor-pro, an open-source single sample MSI scoring method for research and clinical applications. MSIsensor-pro introduces a multinomial distribution model to quantify poly-merase slippages for each tumor sample and a discriminative site selection method to enable MSI detection without matched normal samples. We demonstrate that MSIsensor-pro is an ultrafast, accurate, and robust MSI calling method. Using samples with various sequencing depths and tumor purities, MSIsensor-pro significantly outperformed the current leading methods in both accuracyand computational cost. MSIsensor-pro is available at https://github.com/xjtu-omics/msisensor-pro and free for non-commercial use, while a commercial license is provided upon request.

Objective:To explore the surgical techniques and effects of transfer of the free chimeric functional thoracodorsal artery perforator flap (TDAPF) with latissimus dorsi in reconstruction of dynamic muscle and soft tissue defects in forearm.Methods:From January 2014 to December 2020, a total of 13 transfer surgery of free chimeric functional TDAPF with vascularised latissimus dorsi were performed in the Department of Hand Surgery, Plastic & Reconstructive Surgery, Ningbo Sixth Hospital, to reconstruct forearm composite defects. The patients were 12 males and 1 female with an average age of 33.2 years old. They all had open forearm injuries, with 5 in the left and 8 in the right. Removal of inactivated muscles, exploration and repair of blood vessels and nerves were performed in emergency surgery, and VSD were applied after the surgery. Phase II reconstructive surgery were completed within 4 to 12 days, with 7.5 days in average. The wounds and flaps sized were 9.0 cm×8.0 cm - 21.0 cm×11.0 cm and were 10.0 cm×9.0 cm - 22.0 cm×12.0 cm, respectively. The volume of transferred muscles ranged were 9.0 cm × 2.0 cm × 1.5 cm - 19.0 cm × 9.0 cm × 1.5 cm. Free chimeric functional muscular flaps were transferred to reconstruct the musculus flexor digitorum profundus in 4 patients, the musculus extensor digitorum communis in 8 patients, the musculus flexor carpi radialis in 3 patients, and the musculus flexor pollicis longus in 1 patient. Reconstruction of both of musculus flexor carpi radialis and musculus extensor digitorum communis with 2 functional sub-blocks of latissimus dorsi were performed in 3 patients. All donor sites were closed primarily. All patients were included in the postoperative follow-up to evaluate the appearance of flaps, range of motion of the digits, recovery of muscle strength and gripping power, at the outpatient clinics or through the telephone interview.Results:A total of 12 flaps survived uneventfully after reconstructive surgery. One flap developed a vascular crisis and it was rectified after surgical exploration. Postoperative follow-up ranged from 17 to 52 months, with a mean of 34.1 months. Appearances of limbs and flaps were good without obvious bulky, hyperpigmentation or scar contracture. Four patients with reconstructed musculus flexor digitorum profundus showed muscle strength recovery of M 4, with the fingertips measured lower than 2.0 cm from the centre of palm when clenching a fist, and the average gripping strength of the hand reached 27.5% (20%-35%) to the healthy side. Five patients with reconstructed musculus extensor digitorum communis showed muscle strength recovery of M 4, and there was no obvious limitation in fingers flexion and extension, with the average gripping strength of the hand reached 75.4% (65%-80%) to the healthy side. Of the 3 patients with reconstruction of both power muscles, the recovery of muscle strength of musculus flexor carpi radialis was at M 4 in all the 3 patients, and the musculus extensor digitorum communis was at M 4 in 1 and M 3 in 2 patients. However, the patient who received reconstruction of musculus flexor pollicis had no significant recovery in muscle strength. Conclusion:Transfer of free chimeric functional TDAPF combines the benefits of a perforator flap and a functional muscle transfer together. This surgical technique can effectively reconstruct damaged muscle groups in forearm and resulting in good hand movement. Additionally, it can also restore the aesthetic appearance of forearm, hence makes it an excellent option for complex wound coverage.

Objective    To analyze the expression and clinical significance of cyclin-dependent kinase 1 (CDK1) in lung adenocarcinoma by bioinformatics. Methods    Based on the gene expression data of lung adenocarcinoma patients in The Cancer Genome Atlas (TCGA), the differential expression of CDK1 in lung adenocarcinoma tissues and normal lung tissues was analyzed. The expression of CDK1 gene in lung adenocarcinoma was analyzed by UALCAN at different angles. Survival analysis of different levels of CDK1 gene expression in lung adenocarcinoma was performed using Kaplan-Meier Plotter. Correlation Cox analysis of CDK1 expression and overall survival was based on clinical data of lung adenocarcinoma in TCGA. Gene set enrichment analysis was performed on gene sequences related to CDK1 expression in clinical cases. The protein interaction network of CDK1 from Homo sapiens was obtained by STRING. CDK1-related gene proteins were obtained and analyzed by the web server Gene Expression Profiling Interactive Analysis (GEPIA). Results    Based on the analysis of TCGA gene expression data, CDK1 expression in lung adenocarcinoma was higher than that in normal lung tissues. UALCAN analysis showed that high CDK1 expression may be associated with smoking. Survival analysis indicated that when CDK1 gene was highly expressed, patients with lung adenocarcinoma had a poor prognosis. Univariate and multivariate Cox regression analysis of CDK1 expression and overall survival showed that high CDK1 expression was an independent risk factor for survival of patients with lung adenocarcinoma. Gene set enrichment analysis revealed that high CDK1 expression was closely related to DNA replication, cell cycle, cancer pathway and p53 signaling pathway. Conclusion    CDK1 may be a potential molecular marker for prognosis of lung adenocarcinoma. In addition, CDK1 regulation may play an important role in DNA replication, cell cycle, cancer pathway and p53 signaling pathway in lung adenocarcinoma.

Complex structural variants(CSVs)are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants.How-ever,detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match strategy.As a result,there has been limited progress for CSV discovery com-pared with simple structural variants.Here,we systematically analyzed the multi-breakpoint con-nection feature of CSVs,and proposed Mako,utilizing a bottom-up guided model-free strategy,to detect CSVs from paired-end short-read sequencing.Specifically,we implemented a graph-based pattern growth approach,where the graph depicts potential breakpoint connections,and pattern growth enables CSV detection without pre-defined models.Comprehensive evaluations on both simulated and real datasets revealed that Mako outperformed other algorithms.Notably,validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70％,where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp,respectively.Moreover,the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types,including two novel types of adjacent segment swap and tandem dispersed duplication.Further analysis of these CSVs also revealed the impact of sequence homology on the formation of CSVs.Mako is publicly available at https://github.com/xjtu-omics/Mako.

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na⁺-K⁺-Cl^- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTEN^flox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
Animals ; Drug Resistant Epilepsy/surgery* ; Epilepsy/pathology* ; Malformations of Cortical Development/pathology* ; Malformations of Cortical Development, Group I ; Mice ; Neurons/pathology* ; Seizures/pathology*