Loss of ATM activity induces GADD45α-dependent apoptosis in cerebellar granular neurons / 中山大学学报(医学科学版)

objectiveTo explore the specific molecular mechanism of neuronal apoptosis induced by ATM inactivation. MethodsCGNs matured 7 days in vitro were cultured 8 h with 25 K， 5 K or 25 K medium containing ATM-specific inhibitors （Ku55933， 10 µmol/L； Ku60019， 15 µmol/L） for Hoechst stain and apoptosis analysis， or cultured for different lengths of time （2， 4， 8 h） to detect the protein expression levels of ATM， caspase-3 and cleaved caspase-3 by Western blotting. ATM and GADD45α specific siRNA was transfected into C6 cells and CGNs， and its interference efficiency was verified by q-PCR and Western blotting. CGNs matured for 5 days in vitro were transfected with ATM specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， Hoechst staining and apoptosis analysis were performed. CGNs matured for 7 days in vitro were treated with 25 K medium containing ATM specific inhibitors for 8 h， transcriptome sequencing， differential expression gene identification and pathway enrichment analysis were performed. CGNs matured for 5 days in vitro were co-transfected with GADD45α specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， then treated with 5 K or 25 K medium containing 15 µmol/L Ku6 for 8 h. Hoechst staining and apoptosis analysis were performed. ResultsCompared with the 25 K， CGNs nuclear pyknosis rate， cleaved Caspase-3 and ATM protein expression level were increased in the 5 K and ATM-specific inhibitor groups. The mRNA and protein expression levels of ATM and GADD45α were effectively reduced after transfection of ATM and GADD45α specific siRNA in C6 cells and CGNs. Compared with control， CGNs transfected with ATM specific siRNA showed a higher nuclear pyknosis rate. Totally 835 genes were identified to be up-regulated and 848 genes to be down-regulated in the Ku55933 treatment group； 454 genes were identified to be up-regulated and 314 genes to be down-regulated in the Ku6 treatment group； 274 genes were co-up regulated in the Ku5 and Ku60019 treatment groups， while 179 genes were co-down-regulated in the Ku5 and Ku6 treatment groups and the expression of ATM downstream target GADD45α was upregulated. The enrichment results showed that TNF signaling pathway， NF-κB signaling pathway and Apoptosis signaling pathway were significantly enriched. Compared with control， mRNA and protein expression levels of GADD45α were increased in inhibitor treatment and 5 K， while knocking down GADD45α resulted in a decrease in nuclear pyknosis rate in the Ku60019 and 5 K treatment group. ConclusionLoss of ATM activity induces GADD45α-dependent cerebellar granular neuronal apoptosis.

Comparative study of laparoscopic Keyhole and Sugarbaker technique in the treatment of terminal paracolostomy hernia / 中华外科杂志

Objective: To compare laparoscopic Keyhole repair with Sugarbaker repair in consecutive patients with parastomal hernia. Methods: From January 2015 to December 2021, 117 patients with parastomal hernia were treated with Keyhole or Sugarbaker laparoscopy repairs in the Department of Hernia and Bariatrci Surgery, the First Affiliated Hospital of University of Science and Technology of China, and the clinical data were retrospectively analyzed. There were 45 males and 72 females, aged (68.6±8.6) years (range: 44 to 84 years). Laparoscopic Sugarbaker repair was performed in 89 cases, and Keyhole repair was performed in 28 cases. The t-test, Mann-Whitney U test, χ2 test and Fisher exact test were used to compare the observation indicators between the two groups, such as operation time, incidence of operation-related complications, and postoperative recurrence rate. Results: The follow-up period was (M(IQR)) 33 (36) months (range: 12 to 84 months). Compared to the Sugarbaker group, the hernia ring area of the Keyhole group was bigger (35 (26) cm2 vs. 25 (16) cm2, Z=1.974, P=0.048), length of stay was longer ((22.0±8.0) d vs. (14.1±6.2) d, t=5.485, P<0.01), and the postoperative rate of recurrence was higher (28.6% (8/28) vs. 6.7% (6/89), χ2=7.675, P=0.006). There was no difference in operation time and postoperative complications between the two groups. Conclusions: Laparoscopic Sugarbaker repair is superior to Keyhole repair in the recurrence rate of parastomal hernia treated with compsite mesh (not funnel-shaped mesh). There are no differences in operation time and postoperative complications between the two groups.

Exploration and advance of key techniques in MALDI mass spectrometry imaging / 药学学报

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a new imaging technique with label-free, rapid, and high throughput features. It has bloomed in the analysis on the spatial distribution of biomolecules such as drugs, metabolites, peptides and proteins on the tissue surface in virtue of providing high data throughput from non-targeted full analysis and high accuracy from targeted analysis. The acquisition of MSI signal response with high sensitivity, high spatial resolution, and good stability is directly depended on the appropriate sample preparation approaches, and flexible and various data processing tools will help the non-target data mining to meet the demands of visualization, spatial distribution and multiple index applications so as to reveal the scientific rules beneath the data. This review briefly summarizes the key advances in MALDI-MSI from aspects of sample preparation procedures, data processing and visualization. It also illustrates the characteristics, difficulties and probable solutions derived from these key techniques.

Observation of early clinical efficacy of unilateral biportal endoscopy technique in the treatment of lumbar postoperative adjacent segmental diseases / 中国骨伤

OBJECTIVE@#To investigate early clinical efficacy of unilateral biportal endoscopy technique for the treatment of lumbar postoperative adjacent segmental diseases.@*METHODS@#Fourteen patients with lumbar postoperative adjacent segmental diseases were treated with unilateral biportal endoscopy technique from June 2019 to June 2020. Among them, there were 9 males and 5 females, aged from 52 to 73 years old, and the interval between primary and revision operations ranged from 19 to 64 months. Adjacent segmental degeneration occurred after lumbar fusion in 10 patients and after lumbar nonfusion fixation in 4 patients. All the patients received unilateral biportal endoscopy assisted posterior unilateral lamina decompression or unilateral approach to the contralateral decompression. The operation time, postoperative hospital stay and complications were observed. The visual analogue scale (VAS) of low back pain and leg pain, Oswestry Disability Index (ODI), modified Japanese Orthopaedic Association (mJOA) score were recorded before operation and at 3 days, 3 months, and 6 months after operation.@*RESULTS@#All procedures were successfully completed. Surgical duration ranged from 32 to 151 min. Postoperative CT showed adequate decompression and preservation of most joints. Out of bed walking 1 to 3 days after surgery, postoperative hospital stay was 1 to 8 days, and postoperative follow-up was 6 to 11 months. All 14 patients returned to normal life within 3 weeks after surgery, and VAS, ODI, and mJOA scores improved significantly at 3 days and 3, 6 months after surgery. One patient occurred cerebrospinal fluid leak after operation, received local compression suture, and the wound healed after conservative treatment. One patient occurred postoperative cauda equina neurologic deficit, which was gradually recovered about 1 month after rehabilitation therapy. One patients advented transient pain of lower limbs after surgery, and the symptoms were relieved after 7 days of treatment with hormones, dehydration drugs and symptomatic management.@*CONCLUSION@#Unilateral biportal endoscopy technique has a good early clinical efficacy in the treatment of lumbar postoperative adjacent segmental diseases, which may provide a new minimally invasive, non-fixation option for the treatment of adjacent segment disease.

Treatment of Sanders typeⅡto Ⅲ calcaneal fractures with percutaneous reduction and minimally invasive calcaneal screw fixation / 中国骨伤

OBJECTIVE@#To investigate clinical effect of percutaneous reduction combined with internal fixation of calcaneal nail in treating Sanders typeⅡto Ⅲ calcaneal fractures.@*METHODS@#From July 2017 to August 2019, clinical data of 98 patients with Sanders typeⅡto Ⅲ calcaneal fractures treated were retrospectively analyzed, and divided into observation group and control group according to different surgical methods. In observation group, there were 35 males and 21 females, aged from 23 to 58 years old with an average of (34.50±7.81) years old;29 patients with Sanders typeⅡand 27 patients with Sanders type Ⅲ;30 patients on the left side and 26 patients on the right side;the time from fracture to operation ranged from 1 to 4 days with an average of (3.45±0.54) days;and treated with percutaneous reduction combined with internal fixation of calcaneal nail system. In control group, there were 25 males and 17 females, aged from 25 to 60 years old with an average of (35.27±7.64) years old;23 patients with Sanders type Ⅱ and 19 patients with Sanders type Ⅲ;24 patients on the left side and 18 patients on the right side;the time from fracture to operation ranged from 2 to 5 days with an average of (3.42±0.62) days;and treated with open reduction and internal fixation. Operation time, blood loss, hospital stay, fracture healing time, and postoperative visual analogue scale (VAS) at 1 day, preoperative and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Böhler angle, Gissane angle and calcaneus width, and postoperative complications were compared between two groups.@*RESULTS@#All patients were followed up from 13 to 18 months with an average of (15.6±2.2) months. There were significant differences in operation time, blood loss, hospital stay, fracture healing time and postoperative VAS at 1 day between two groups (P<0.05). There was statistical difference in postoperative AOFAS score at 12 months between two groups (P<0.05), and AOFAS score at 12 months after operation was higher than that before operation (P<0.05). According to AOFAS score, 21 patients got excellent result, 30 good and 5 moderate in observation group, and 10 excellent, 22 good, 7 moderate and 3 poor in control group, which had statistical difference between two groups (P<0.05). Postoperative Böhler angle, Gissane angle and calcaneus width at 6 months were better than that before operation between two groups(P<0.05). One patient in observation and 20 patients in control group occurred skin numbness after operation, and 14 patients occurred skin necrosis in control group, there were obvious difference between two groups(P<0.01).@*CONCLUSION@#Compared with open reduction and internal fixation, percutaneous reduction combined with internal fixation system in treating Sanders typeⅡto Ⅲ calcaneal fractures is feasible for fracture repair without waiting for foot deswelling, which could accurately restore normal shape and position of the fractured heel bone, completely eliminate fracture malunion, and reduce postoperative complications. Therefore, it could shorten operation time, hospital stay, fracture healing time, reduce amount of blood loss, promote postoperative recovery, and less complications, high safety, which could be used as a choice of orthopedic surgery for foot and ankle trauma.

Diagnosis and treatment of finger flexion contracture caused by forearm flexor disease / 中国修复重建外科杂志

OBJECTIVE@#To summarize the clinical characteristics, differential diagnosis, and treatment methods of finger flexion contracture caused by three kinds of forearm flexor diseases.@*METHODS@#Between December 2008 and August 2021, 17 patients with finger flexion contracture were treated, including 8 males and 9 females, aged 5-42 years, with a median of 16 years. The disease duration ranged from 1.5 months to 30 years, with a median of 13 years. The etiology included 6 cases of Volkmann's contracture, all of which were flexion deformity of the 2nd to 5th fingers, accompanied by limitation of thumb dorsiflexion in 3 cases and limitation of wrist dorsiflexion in 3 cases; 3 cases of pseudo-Volkmann's contracture, including 2 cases of flexion deformity of middle, ring, and little fingers, and 1 case of flexion deformity of ring and little fingers; 8 cases of ulnar finger flexion contracture caused by forearm flexor disease or anatomical variations, all of which were flexion deformity of middle, ring, and little fingers. Operations such as slide of flexor and pronator teres origin, excision of abnormal fibrous cord and bony prominence, and release of entrapped muscle (tendon) were performed. Hand function was evaluated according to WANG Haihua's hand function rating standard or modified Buck-Gramcko classification standard, and muscle strength was evaluated according to British Medical Research Council (MRC) muscle strength rating standard.@*RESULTS@#All patients were followed up 1-10 years (median, 1.5 years). At last follow-up, 8 patients with contracture caused by forearm flexor disease or anatomical variations and 3 patients with pseudo-Volkmann's contracture achieved excellent hand function, with muscle strength of grade M5 in 6 cases and grade M4 in 5 cases. One patient with mild Volkmann's contracture and 3 patients with moderate Volkmann's contracture without severe nerve damage had excellent hand function in 2 cases and good in 2 cases, with muscle strength of grade M5 in 1 case and grade M4 in 3 cases. Two patients with moderate or severe Volkmann's contracture had poor hand function, with 1 case of muscle strength of grade M3 and 1 case of grade M2, which improved when compared with those before operation. The overall excellent and good rate of hand function and the proportion of patients with muscle strength of grade M4 and above were 88.2% (15/17), respectively.@*CONCLUSION@#The finger flexion contracture caused by different etiology can be differentiated by analyzing the history, physical examination, radiographs, and intraoperative findings. After different surgical treatments, such as resection of contracture band, release of compressed muscle (tendon), and downward movement of flexor origin, most patients have a good outcome.

Progress in stimuli-responsive molecularly imprinted polymers for enrichment analysis of trace components in traditional Chinese medicine / 中国中药杂志

Molecularly imprinted polymers demonstrate outstanding performance in the research on trace ingredients because of their high selectivity. Stimuli-responsive molecularly imprinted polymers(STR-MIPs) with the introduction of different responsive groups on the basis of traditionally imprinted materials can undergo reversible transformations when exposed to external stimuli such as temperature, magnetism, pH or light. Such responsiveness, combined with the specific recognition, endows STR-MIPs with excellent perfor-mance in trace component studies. Traditional Chinese medicine(TCM) contains complex components with trace content, and thus STR-MIPs have broad application prospects in the enrichment analysis of trace components in TCM. This paper elaborates on the application of STR-MIPs in the enrichment analysis of trace components in TCM from the perspectives of different stimuli, summarized relevant research achievements in the recent five years to broaden the application fields of molecular imprinting, and proposed a few opi-nions about their future development.

Clinical significance of pathological diagnosis and genetic abnormalities detection in gastrointestinal stromal tumor using endoscopic biopsy / 中华病理学杂志

Objective: To investigate the clinical significance of pathological diagnosis and genetic abnormalities detection of gastrointestinal stromal tumor (GIST) using endoscopic biopsy. Methods: Patients with GIST diagnosed by endoscopic biopsy (from January 1st, 2016 to August 1st, 2018, at Zhongshan Hospital, Fudan University) were included in this study. This retrospective study evaluated the histopathologic and immunohistochemical (IHC) features, genetic abnormalities of the tumors and the treatment and clinical course of the patients. Results: Totally 4 095 cases of GIST were collected, among which 67 patients (67/4 095, 1.6%) underwent endoscopic biopsy. Forty-eight patients (71.6%) were male and 19 (28.4%) were female, with a mean age of 61 years (range 31-90 years). Fifty-nine lesions were located in stomach and eight in duodenum. Of all the 67 cases, 47 were spindle type, 14 were epithelioid type, and 6 mixed type. IHC staining showed the positive rates were 100.0% (64/64) for DOG1, 98.4% (62/63) for CD117, 87.5% (56/64) for CD34, 3.6% (2/56) for S-100 protein, 12.1% (7/58) for α-SMA, 12.3% (7/57) for desmin and 4.0% (2/50) for CKpan. Morphologically, 34 cases were malignant; three cases (all epithelioid type) were originally misdiagnosed as poorly differentiated carcinoma; missed-diagnosis were found in four cases (spindle type) due to the insufficient diagnostic tumor cells. The genetic abnormality detection rate in the biopsy tissue was 38.8% (26/67),among them two patients were lost to follow up after biopsy, 33 patients received surgical resection, 16 cases underwent operation after neoadjuvant therapy and 16 patients with advanced disease underwent continuous imatinib therapy, with the genetic testing rate of 6.1% (2/33), 10/16 and 14/16, respectively. Conclusions: Endoscopic biopsy is a useful but rare method for the preoperative diagnosis of GIST. For majority of biopsy, accurate pathological diagnosis and auxiliary examination can be completed to guide clinical treatment. A thorough history in combination with endoscopic finding is essential to avoid misdiagnosis (epithelioid type) and missed diagnosis (spindle type) in suspicious cases. Genetic testing should be recommended in patients who will undergo targeted therapy after endoscopic biopsy, and it can provide valuable information and guidance for clinical treatment.

Genomic structure of varicella-zoster virus and its vaccine application status / 中华预防医学杂志

With the determination of the whole genome sequence of varicella-zoster virus (VZV) virus, the successful breakthrough of infectious cloning technology of VZV, and the emergence of effective preventive vaccines, which have been proven to be effective and safe, varicella has become a disease preventable by specific immunity. This article will review the genomic structure, epidemiological characteristics, and research application progress of varicella vaccine and herpes zoster vaccine of varicella zoster virus to provide reference for primary prevention of the disease.

Clinical observation on electroacupuncture at "four points of sacral region" on moderate to severe stress urinary incontinence after radical prostatectomy / 中国针灸

OBJECTIVE@#To compare the clinical therapeutic effect between electroacupuncture at "four points of sacral region" and transurethral Erbium laser in treatment of moderate to severe stress urinary incontinence after radical prostatectomy.@*METHODS@#A total of 68 patients of moderate to severe stress urinary incontinence after radical prostatectomy were divided into an electroacupuncture group (34 cases) and an Erbium laser group (34 cases, 3 cases dropped off) according to the settings. In the electroacupuncture group, electroacupuncture was applied at "four points of sacral region", i.e. points of 0.5 cun beside bilateral sacrococcygeal joints and bilateral Huiyang (BL 35), with continuous wave, 2 Hz in frequency, 60 min each time, once every other day, 3 times a week, 12 times as one course of treatment. In the Erbium laser group, transurethral Erbium laser technology was given, once every 4 weeks as one course of treatment. Both groups were treated for 5 courses. The scores of the International Consultation on Incontinence questionnaire-short form (ICI-Q-SF) and the incontinence quality of life questionnaire (I-QOL) were observed before treatment, after each course of treatment and in follow-up after 1 and 2 months of treatment completion, respectively, and the clinical efficacy was evaluated after treatment in the two groups.@*RESULTS@#Compared with those before treatment, the ICI-Q-SF scores were decreased while the I-QOL scores were increased after 5 courses of treatment and in follow-up after 1, 2 months of treatment completion in the two groups (P<0.01). The ICI-Q-SF score in follow-up after 2 months of treatment completion were higher than that after 5 courses of treatment in the Erbium laser group (P<0.05). After 3, 4, 5 courses of treatment and in follow-up after 1 and 2 months of treatment completion, the ICI-Q-SF scores in the electroacupuncture group were lower than those in the Erbium laser group (P<0.05, P<0.01); after 2, 3, 4, 5 courses of treatment and in follow-up after 1 and 2 months of treatment completion, the I-QOL scores in the electroacupuncture group were higher than those in the Erbium laser group (P<0.01). The change ranges of ICI-Q-SF score and I-QOL score between before treatment and after each course of treatment in the electroacupuncture group were lager than those in the Erbium laser group (P<0.01, P<0.05). The total effective rate was 61.8% (21/34) in the electroacupuncture group, which was superior to 19.4 (6/31) in the Erbium laser group (P<0.01).@*CONCLUSION@#Both electroacupuncture at "four points of sacral region" and transurethral Erbium laser can improve the clinical symptoms and the quality of life in patients of moderate to severe stress urinary incontinence after radical prostatectomy. The short-term efficacy and long-term efficacy of electroacupuncture are superior to the Erbium laser technology.

Investigation and analysis of underground noise in Sichuan coal mines / 中华劳动卫生职业病杂志

Objective: To understand the harm degree of underground noise and provide basis for noise control. Methods: In November 2019, 13 typical coal mines in Sichuan Province were selected as the research objects, and a total of 1203 sites and 609 jobs of noise exposure were investigated. Results: The noise intensity P75 >80 dB (A) was measured. The noise intensity of the inspection place of the air compressor is >86 dB (A) , the noise intensity of the inspection place of the gas drainage and the operation place of the main fan is between 80-85 dB (A) . Conclusion: Besides the harm of dust, noise exposure should also be paid attention to, and the measures of sound absorption and sound insulation should be taken or personal protection should be strengthened.

Relationship between body mass index and sexual development in Chinese children / 中华儿科杂志

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.

Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019 / 中华外科杂志

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during 2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

Analysis of characteristics and trends of randomized controlled trials of gastric cancer between 2000 and 2019 / 中华外科杂志

Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.

Casticin inhibits the proliferation, migration and invasion of bladder cancer cells by inhibition of TM7SF4 expression / 中华肿瘤杂志

Objective: To explore the effect and mechanism of Casticin (CAS) on the proliferation, migration and invasion of bladder cancer T24 cells. Methods: T24 cells were cultured in vitro and divided into control group, 5, 10, 20 μmol/L CAS groups, si-NC group, si-TM7SF4 group, CAS+ pcDNA group and CAS+ pcDNA-TM7SF4 group. Cell counting kit-8 (CCK-8) was used to detect cell proliferation; Transwell was used to detect cell migration and invasion; western blot was used to detect the protein expressions of cyclin D1, p21, MMP-2, MMP-9 and TM7SF4, and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of TM7SF4 mRNA. Results: The inhibition rates of T24 cells in the 5, 10, 20 μmol/L CAS groups were (17.68±1.41)%, (33.54±3.16)% and (61.44±5.50)%, respectively, higher than (0.00±0.00)% of the control group (P<0.001), but the numbers of migration and invasion were 72.83±5.66, 59.13±4.27, 41.25±3.22 and 55.83±5.15, 42.19±3.06, 31.13±3.22, respectively, lower than 86.11±5.16 and 68.82±5.29 of the control group (P<0.001). The protein expression levels of cyclin D1, MMP-2, MMP-9, TM7SF4 and the expression levels of TM7SF4 mRNA in the 5, 10, and 20 μmol/L CAS groups were lower than the control group (P<0.001). However, the protein expression levels of p21 were 0.37±0.03, 0.51±0.04, and 0.66±0.06, respectively, higher than 0.25±0.03 in the control group (P<0.001). The inhibition rate of T24 cells in the si-TM7SF4 group was (50.35±4.67)%, higher than (6.31±0.58)% in the si-NC group (P<0.001), but the numbers of migration and invasion were 53.51±4.18 and 42.92±3.81, lower than 85.26±4.99 and 67.93±4.64 of the si-NC group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2, MMP-9 in the si-TM7SF4 group were lower than the si-NC group (P<0.001). However, the protein expression level of p21 in the si-TM7SF4 group was higher than the si-NC group (P<0.001). The inhibitory rate of T24 cells in the CAS+ pcDNA-TM7SF4 group was (21.45±2.46)%, lower than (64.06±4.49)% of the CAS+ pcDNA group (P<0.001), but the number of migration and invasion in the CAS+ pcDNA-TM7SF4 group were 75.66±6.57 and 59.35±5.40, higher than 40.43±3.85 and 30.25±3.32 in the CAS+ pcDNA group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2 and MMP-9 in the CAS+ pcDNA-TM7SF4 group were higher than the CAS+ pcDNA group (P<0.001), but the protein expression level of p21 was lower than the CAS+ pcDNA group (P<0.001). Conclusion: CAS may suppress the proliferation, migration and invasion of bladder cancer T24 cells by inhibiting the expression of TM7SF4.

The expression of cortactin in colorectal cancer and its relationship with clinicopathological and prognostic parameters / 中华肿瘤杂志

Objective: To investigate the expression of cortactin in colorectal cancer and its correlation with clinicopathological parameters and prognosis. Methods: The expressions of cortactin in normal colorectal mucosal tissue and colorectal cancer tissue in paraffin-embedded tissue microarray from 319 patients who were diagnosed as colorectal cancer and treated in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2009 was detected by immunohistochemistry. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox proportional risk regression model was used for multivariate analysis. Results: The positive expression rates of cortactin in colorectal cancer tissue and normal colorectal mucosal tissue were 61.1% (195/319) and 5.6% (18/319, P<0.001), respectively. T-stage, N-stage, American Joint Committee on Cancer (AJCC) stage, degree of tumor differentiation, neural invasion and preoperative carcinoembryonic antigen (CEA) levels were associated with the expression of cortactin (P<0.05). The positive expression of cortactin was associated with poorer disease-free survival (P=0.036) and overall survival (P=0.043), and the effect was more significant in patients with stage Ⅱ to Ⅲ. For patients with stage Ⅱ-Ⅲ colorectal cancer, postoperative adjuvant therapy was associated with disease-free survival (P=0.007) and overall survival (P=0.015). The vascular tumor embolus, pathological type, preoperative CEA level and cortactin expression were independent influencing factors for disease-free survival (P<0.05). The age, AJCC stage, preoperative CEA level and cortactin expression were independent influencing factors for overall survival (P<0.05). Preoperative CEA level and cortactin expression were independent influencing factors for disease-free survival and overall survival (P<0.05). Conclusion: Cortactin is expressed in colorectal cancer and in stage Ⅱ-Ⅲ patients, it is a potential predictor of colorectal cancer prognosis.

Application and prospect of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal metastasis from colorectal cancer / 中华肿瘤杂志

Colorectal cancer is one of the common malignant tumors in China, and its incidence is increasing with years. As the second most common metastatic site of colorectal cancer, peritoneum is difficult to diagnose early and with a poor prognosis. Systemic intravenous chemotherapy was used as the main treatment strategy for peritoneal metastasis in the past, but its systemic toxic and side effects were obvious, and it could not effectively control tumor progression. In recent years, the continuous development of surgical techniques, concepts, and equipment, as well as the introduction of new chemotherapy drugs and targeted drugs have significantly improved the quality of life and prognosis of patients with peritoneal metastasis of colorectal cancer. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can effectively eradicated the intraperitoneal free cancer cells and subclinical lesions, while reducing systemic side effects of chemotherapy drugs, and achieve the radical cure of the tumor at the macro and micro levels to the greatest extent. It has been used as the first-line treatment program for peritoneal metastasis of colorectal cancer at home and abroad. This article focuses on the analysis and summary of the survival efficacy, prognostic factor analysis, and chemotherapy safety of CRS+ HIPEC in the treatment of colorectal cancer peritoneal metastasis. The existing problems and controversies of HIPEC therapy are discussed simultaneously.

Effects of gender on clinical outcomes in extremely low birth weight infants and analysis of risk factors of mortality / 中国新生儿科杂志

Objective:To study the effects of gender on clinical outcomes of extremely low birth weight infants (ELBWI) and to analyze the risk factors of mortality.Methods:From January 2011 to December 2020, ELBWI (birth weight <1 000 g) admitted to the Neonatology Department of our hospital were retrospectively studied. The infants were assigned into the male group and the female group. Incidences of major complications, survival rate and mortality rate were compared between the two groups. The infants were also assigned into survival group and death group according to their clinical outcomes. Binary multivariate unconditional Logistic regression was used to analyze the risk factors of mortality in ELBWI.Results:A total of 637 ELBWI cases were included. 311 cases were in the male group with a survival rate of 57.9% (180/311) and 326 cases were in the female group with a survival rate of 57.4% (187/326). The incidences of neonatal respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), pulmonary hemorrhage and severe intraventricular hemorrhage (IVH) in the male group were significantly higher than the female group ( P<0.05). Significant increases of survival rate existed for both groups year by year ( P<0.01).No significant differences existed in survival rate, mortality rate of infants receiving proactive treatment and mortality rate of infants withdrawing treatment between the two groups ( P>0.05). Multivariate unconditional Logistic regression analysis showed that withdrawing treatment ( P<0.01) and pulmonary hemorrhage ( P<0.05) were associated with increased risks of mortality. Conclusions:Male ELBWI have higher risks of RDS, BPD and severe IVH than female ELBWI. Withdrawing treatment and pulmonary hemorrhage are common risk factors of mortality for both male and female ELBWI.

Effect of artificial liver with double plasma molecular absorb system model on patients' platelets and corresponding treatment strategy / 北京大学学报(医学版)

OBJECTIVE@#To compare the effects of artificial liver treatment with double plasma molecular adsorption system(DPMAS) mode and traditional plasma exchange (PE) mode on platelets in patients, and to evaluate the clinical efficacy of recombinent human thrombopoietin (rhTPO) in the treatment of thrombocytopenia.@*METHODS@#A total of fifteen patients undergoing artificial liver with DPMAS model admitted to the Fifth Affiliated Hospital of Guangzhou Medical University from January 2018 to November 2020 were selected and included in the DPMAS group, and another 15 patients receiving PE were selected and included in the PE group. The improvement of clinical symptoms, such as fatigue, jaundice, oliguria, edema, etc. before and after artificial liver treatment was compared between the two groups, and the trend of blood routine (especially platelet), coagulation function and other indexes before and after treatment were compared between the two groups. The use of rhTPO and the number of platelets were recorded during treatment.@*RESULTS@#The improvement rate of clinical symptoms in DPMAS group was 86.67%, which was higher than that in PE group, but the difference was not statistically significant (P>0.05). There was no statistical significance in the outcome of the two groups within 90 days (P>0.05). There was no significant difference in white blood cell (WBC) and hemoglobin (HB) between the two groups after treatment (P>0.05). However, the level of platelet(PLT) in DPMAS group was significantly lower than that before treatment (P < 0.05), and was significantly lower than that in PE group (P < 0.05). After treatment, the international normalized ratio (INR) level in PE group was significantly improved (P < 0.05), but there was no significant difference in the INR level in DPMAS group (P>0.05). The patients in the DPMAS group received an average of (8.2±3.1) doses of rhTPO and (1.5±0.3) IU of platelet transfusions during hospitalization. In DMPAS group, platelets increased significantly after infusion of terbium.@*CONCLUSION@#Compared with PE mode, the artificial liver with DPMAS mode can reduce platelet levels in patients, but the application of rhTPO can stimulate platelet regeneration and increase platelet levels in the patients, thereby reducing the risk of bleeding due to platelet hypoplasia.

Mechanism of Tingli Dazao Xiefeitang on Cell Pyrolysis and Apoptosis Induced by Caspase-1 in A549 Cells / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of coking death and apoptosis of A549 cells induced by Tingli Dazao Xiefeitang. MethodA549 cells were randomized into blank group， traditional Chinese medicine（TCM） low， medium， and high concentration groups， which were treated with 20， 40， 60 mg·L-1 Tingli Dazao Xiefeitang， and TCM low， medium， and high concentration groups， respectively， and blank group was treated with equal volume culture medium. After 48 h of treatment， cell migration was detected by scratch assay and cell apoptosis was detected by flow cytometry. The relative expression levels of cysteine aspartate protease-1（Caspase-1）， NOD-like receptor protein 3 （NLRP3）， dermoderin D （GSDMD）， Survivin protein and nuclear transcription factor -κB （NF-κB） pathway proteins were detected by Western blot. The levels of intracellular reactive oxygen species （ROS） were determined by DCFH-DA fluorescence probe， and the contents of tumor necrosis factor -β （TNF-β） and interleukin-1β （IL-1β） in supernatant were determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with blank group， the scratch healing rate， apoptosis rate， relative expression of Survivin protein， Caspase-1， GSDMD， NLRP3， ROS and NF-κB phosphorylation levels were significantly increased in low， medium and high concentration groups. The contents of TNF-β and IL-1β in supernatant were significantly increased （P<0.05）. Compared with the low concentration group， the scratch healing rate， apoptosis rate， Survivin protein relative expression， Caspase-1， GSDMD， NLRP3 relative expression， ROS and NF-κB phosphorylation levels were significantly increased in the medium and high concentration groups. The contents of TNF-β and IL-1β in supernatant were significantly increased （P<0.05）. Compared with the TCM group， the scratch healing rate， apoptosis rate， Survivin protein relative expression， Caspase-1， GSDMD， NLRP3 relative expression， ROS and NF-κB phosphorylation levels were significantly increased in the high concentration group. The contents of TNF-β and IL-1β in supernatant were significantly increased （P<0.05）. ConclusionTingli Dazao Xiefeitang can improve NLRP3 protein expression， inhibit Survivin protein expression and promote apoptosis of A549 cells. At the same time， it can activate NF-κB pathway and ROS system， up-regulate the expression of Caspase-1 and GSDMD， mediate scortosis of A549 cells.