Recent advances in drug screening methods of SARS-CoV-2 spike protein / 药学学报

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Application and value of intravascular ultrasound for excimer laser ablation combined with drug-coated balloon in the treatment of lower limb arteriosclerotic obliterans / 中华外科杂志

Objective: To examine the value of intravascular ultrasound (IVUS) for excimer laser ablation (ELA) combined with drug-coated balloon (DCB) in treating lower limb arteriosclerotic obliterans (ASO). Methods: As a prospective case series study, patients who underwent ELA combined with DCB for lower limb ASO with the guidance of IVUS from September 2021 to March 2022 at Department of Vascular Surgery, Zhongshan Hospital, Fudan University were enrolled prospectively. Lesion characteristics, procedure-related outcomes and complications were collected. The therapy outcomes were compared with baseline data by paired t test. Results: There were 8 males and 2 females, aged (72.0±5.9) years (range: 61 to 81 years). Of all the 11 lesions, there were 8 lesions in superficial femoral artery and 3 in popliteal artery. The lesion length was (7.0±2.4) cm (range: 3.2 to 9.8 cm). There were 4 chronic totally occlusion and 7 severe stenosis. All patients underwent the operation successfully. The technical success rate was 10/11. Bailout stenting was performed in one lesion because of flow-limiting dissection. Four lesions were grade 3 to 4 in peripheral artery calcium score system, and 9 lesions with calcification arc≥180°. Larger diameter drug-coated balloons were selected in 5 lesions after measurement of intravascular ultrasound. The follow-up time was (6.0±1.9) months (range: 3 to 9 months). The ankle-brachial index of the patient was significantly improved immediately after surgery (0.97±0.13 vs. 0.48±0.18, t=-7.60, P<0.01) and at 3 months after surgery (0.95±0.12 vs. 0.48±0.18, t=-7.17, P<0.01). The 3-month primary patency rate was 11/11, the target lesion reintervention was 0 and ulcer healing rate was 3/4. Conclusion: IVUS assisted ELA in the treatment of lower limb artery lesions is safe and effective in early stage.

Active Ingredients of Reduning Injection Maintain High Potency against SARS-CoV-2 Variants / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin.@*METHODS@#A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43.@*RESULTS@#The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC50) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC50 lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43.@*CONCLUSIONS@#The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.

The impact of extended waiting time on tumor regression after neoadjuvant chemoradiotherapy for locally advanced rectal cancer / 中华外科杂志

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ2 test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9th to <10th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ2=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ2=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ2=1.878, P=0.171; χ2=0.078, P=0.780; χ2=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

A Novel Early Warning Model for Hand, Foot and Mouth Disease Prediction Based on a Graph Convolutional Network / 生物医学与环境科学（英文）

Objectives@#Hand, foot and mouth disease (HFMD) is a widespread infectious disease that causes a significant disease burden on society. To achieve early intervention and to prevent outbreaks of disease, we propose a novel warning model that can accurately predict the incidence of HFMD.@*Methods@#We propose a spatial-temporal graph convolutional network (STGCN) that combines spatial factors for surrounding cities with historical incidence over a certain time period to predict the future occurrence of HFMD in Guangdong and Shandong between 2011 and 2019. The 2011-2018 data served as the training and verification set, while data from 2019 served as the prediction set. Six important parameters were selected and verified in this model and the deviation was displayed by the root mean square error and the mean absolute error.@*Results@#As the first application using a STGCN for disease forecasting, we succeeded in accurately predicting the incidence of HFMD over a 12-week period at the prefecture level, especially for cities of significant concern.@*Conclusions@#This model provides a novel approach for infectious disease prediction and may help health administrative departments implement effective control measures up to 3 months in advance, which may significantly reduce the morbidity associated with HFMD in the future.

Fucoxanthin regulates Nrf2/Keap1 signaling to alleviate myocardial hypertrophy in diabetic rats / 南方医科大学学报

OBJECTIVE@#To investigate the protective effect of fucoxanthin (FX) against diabetic cardiomyopathy and explore the underlying mechanism.@*METHODS@#Rat models of diabetes mellitus (DM) induced by intraperitoneal injection of streptozotocin (60 mg/kg) were randomized into DM model group, fucoxanthin treatment (DM+FX) group and metformin treatment (DM+ Met) group, and normal rats with normal feeding served as the control group. In the two treatment groups, fucoxanthin and metformin were administered after modeling by gavage at the daily dose of 200 mg/kg and 230 mg/kg, respectively for 12 weeks, and the rats in the DM model group were given saline only. HE staining was used to examine the area of cardiac myocyte hypertrophy in each group. The expression levels of fibrotic proteins TGF-β1 and FN proteins in rat hearts were detected with Western blotting. In the cell experiment, the effect of 1 μmol/L FX on H9C2 cell hypertrophy induced by exposure to high glucose (HG, 45 mmol/L) was evaluated using FITC-labeled phalloidin. The mRNA expression levels of the hypertrophic factors ANP, BNP and β-MHC in H9C2 cells were detected using qRT-PCR. The protein expressions of Nrf2, Keap1, HO-1 and SOD1 proteins in rat heart tissues and H9C2 cells were determined using Western blotting. The DCFH-DA probe was used to detect the intracellular production of reactive oxygen species (ROS).@*RESULTS@#In the diabetic rats, fucoxanthin treatment obviously alleviated cardiomyocyte hypertrophy and myocardial fibrosis, increased the protein expressions of Nrf2 and HO-1, and decreased the protein expressions of Keap1 in the heart tissue (P < 0.05). In H9C2 cells with HG exposure, fucoxanthin significantly inhibited the enlargement of cell surface area, lowered the mRNA expression levels of ANP, BNP and β-MHC (P < 0.05), promoted Nrf2 translocation from the cytoplasm to the nucleus, and up-regulated the protein expressions its downstream targets SOD1 and HO-1 (P < 0.05) to enhance cellular antioxidant capacity and reduce intracellular ROS production.@*CONCLUSION@#Fucoxanthin possesses strong inhibitory activities against diabetic cardiomyocyte hypertrophy and myocardial fibrosis and is capable of up-regulating Nrf2 signaling to promote the expression of its downstream antioxidant proteins SOD1 and HO-1 to reduce the level of ROS.

Clinical efficacy and prognosis of simultaneous resection of synchronous colorectal liver metastasis in patients admitted in different phases / 中华消化外科杂志

Objective:To investigate the clinical efficacy and prognosis of simultaneous resection of synchronous colorectal liver metastasis in patients admitted in different phases.Methods:The retrospective cohort study was conducted. The clinicopathological data of 346 patients who underwent simultaneous resection of synchronous colorectal liver metastasis in the First Affiliated Hospital of Naval Medical University (Changhai Hospital of Shanghai) from January 2000 to April 2021 were collected. There were 217 males and 129 females, aged (58±12)years. Patients under-went simultaneous resection of synchronous colorectal liver metastasis. Observation indicators: (1) clinicopathological features of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021; (2) surgical and postoperative situations of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021; (3) analysis of prognosis of patients with synchro-nous colorectal liver metastasis in 2000?2010 and 2011?2021. Follow-up was conducted using telephone interview or outpatient examination to detect survival of patients. The follow-up was performed once every 3 months, including blood routine test, liver and kidney function test, car-cinoembryonic antigen (CEA) test, CA19-9 test, abdominal B-ultrasound examination, and once every 6 months, including chest computed tomography (CT) plain scan, liver magnetic resonance imaging (MRI) and/or CT enhanced scan, abdominal or pelvic MRI and/or CT enhanced scan, within postoperative 2 year. The follow-up was performed once every 6?12 months within postoperative 2?5 years including above reexaminations. Electronic colonoscopy was performed once a year after operation. The follow-up was up to November 12, 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distuibution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-Rank test was used to conduct survival analysis. Results:(1) Clinicopathological features of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021. Of the 346 patients, 59 cases underwent simultaneous resection within 2000?2010 and 287 cases underwent simultaneous resection within 2011?2021. The gender (males and females), cases with or without fundamental diseases, cases with the number of lymph nodes harvested in primary lesion as <12 or ≥12, the tumor diameter of primary lesion, the tumor diameter of liver metastasis lesion, the number of liver metastasis lesions, cases with or without preoperative treatment, cases with or without postoperative treatment, cases with adjuvant therapy as perioperative treatment, surgery or other treatment were 47, 12, 36, 23, 19, 40, (5.5±2.4)cm, (2.1±0.7)cm, 1.6±0.5, 59, 0, 16, 16, 0, 16, 43 in patients admitted in 2000?2010, respectively. The above indicators in patients admitted in 2011?2021 were 170, 117, 121, 166, 58, 229, (4.2±2.0)cm, (3.0±2.0)cm, 1.9±1.4, 208, 79, 34, 235, 74, 29, 184, respectively. There were significant differences in the above indicators between patients admitted in 2000?2010 and 2011?2021 ( χ2=8.73, 7.02, 4.07, t= 4.40, ?6.04, ?3.10, χ2=21.05, 28.82, 26.68, P<0.05). (2) Surgical and postoperative situations of patients with synchronous colorectal liver metastasis in 2000?2010 and 2011?2021. Cases with surgical methods as complete open surgery or laparoscopy combined with open surgery, the operation time, time to postoperative initial liquid food intake, cases with or without postoperative complications, cases with postoperative duration of hospital stay as ≤10 days or >10 days were 58, 1, (281±57)minutes, (5±1)days, 33, 26, 14, 45 in patients admitted in 2000?2010, respec-tively. The above indicators in patients admitted in 2011?2021 were 140, 147, (261±82)minutes, (3±1)days, 233, 54, 198, 89, respectively. There were significant differences in the above indicators between patients admitted in 2000?2010 and 2011?2021 ( χ2=49.04, t=2.24, 7.53, χ2=17.56, 26.02, P<0.05). There was no death in the 346 patients. (3) Analysis of prognosis of patients with synchro-nous colorectal liver metastasis in 2000?2010 and 2011?2021. Of the 346 patients, 295 cases were followed up for 47(range, 1?108)months. Of the 29 patients admitted in 2000?2010 who were followed up, there were 27 cases died. The median survival time, 1-, 3-, 5-year overall survival rates, 1-, 3-, 5-year disease free survival rates of patients admitted in 2000?2010 were 18.0 months (95% confidence interval as 12.7?23.3 months), 82.8%, 11.5%, 3.8%, 53.6%, 8.3%, 4.2%, respec-tively. Of the 266 patients admitted in 2011?2021 who were followed up, there were 109 cases died. The median survival time, 1-, 3-, 5-year overall survival rates, 1-, 3-, 5-year disease free survival rates of patients admitted in 2011?2021 were 54.0 months (95% confidence interval as 38.1?70.4 months), 93.3%, 61.8%, 47.0%, 68.2%, 33.7%, 28.3%, respectively. There were significant differences in overall survival rate and disease free survival rate between patients admitted in 2000?2010 and 2011?2021 ( χ2=47.57, 9.17, P<0.05). Conclusions:With the increase of the operation volume of simultaneous resection of synchronous colorectal liver metastasis, the operation time, time to postoperative initial liquid food intake, postoperative duration of hospital stay and postoperative complications have significantly decreased, while the overall survival rate and disease free survival rate have significantly increased.

A prospective cohort study on the clinical value of pelvic peritoneal reconstruction in laparoscopic anterior resection for middle and low rectal cancer / 中华胃肠外科杂志

Objective: To investigate the safety and efficacy of pelvic peritoneal reconstruction and its effect on anal function in laparoscopy-assisted anterior resection of low and middle rectal cancer. Methods: A prospective cohort study was conducted. Consecutive patients with low and middle rectal cancer who underwent laparoscopy-assisted transabdominal anterior resection at Naval Military Medical University Changhai Hospital from February 2020 to February 2021 were enrolled. Inclusion criteria: (1) the distance from tumor to the anal verge ≤10 cm; (2) laparoscopy-assisted transabdominal anterior resection of rectal cancer; (3) complete clinical data; (4) rectal adenocarcinoma diagnosed by postoperative pathology. Exclusion criteria: (1) emergency surgery; (2) patients with a history of anal dysfunction or anal surgery; (3) preoperative diagnosis of distant (liver, lung) metastasis; (4) intestinal obstruction; (5) conversion to open surgery for various reasons. The pelvic floor was reconstructed using SXMD1B405 (Stratafix helical PGA-PCL, Ethicon). The first needle was sutured from the left anterior wall of the neorectum to the right. Insertion of the needle was continued to suture the root of the sigmoid mesentery while the Hemo-lok was used to fix the suture. The second needle was started from the beginning of the first needle, after 3-4 needles, a drainage tube was inserted through the left lower abdominal trocar to the presacral space. Then, the left peritoneal incision of the descending colon was sutured, after which Hemo-lok fixation was performed. The operative time, perioperative complications, postoperative Wexner anal function score and low anterior resection syndrome (LARS) score were compared between the study group and the control group. Three to six months after the operation, pelvic MRI was performed to observe and compare the pelvic floor anatomical structure of the two groups. Results: A total of 230 patients were enrolled, including 58 who underwent pelvic floor peritoneum reconstruction as the study group and 172 who did not undergo pelvic floor peritoneum reconstruction as the control group. There were no significant differences in general data between the two groups (all P>0.05). The operation time of the study group was longer than that of control group [(177.5±33.0) minutes vs. (148.7±45.5) minutes, P<0.001]. There was no significant difference in the incidence of perioperative complications (including anastomotic leakage, anastomotic bleeding, postoperative pneumonia, urinary tract infection, deep vein thrombosis, and intestinal obstruction) between the two groups (all P>0.05). Eight cases had anastomotic leakage, of whom 2 cases (3.4%) in the study group were discharged after conservative treatment, 5 cases (2.9%) of other 6 cases (3.5%) in the control group were discharged after the secondary surgical treatment. The Wexner score and LARS score were 3.1±2.8 and 23.0 (16.0-28.0) in the study group, which were lower than those in the control group [4.7±3.4 and 27.0 (18.0-32.0)], and the differences were statistically significant (t=-3.018, P=0.003 and Z=-2.257, P=0.024). Severe LARS was 16.5% (7/45) in study group and 35.5% (50/141) in control group, and the difference was no significant differences (Z=4.373, P=0.373). Pelvic MRI examination 3 to 6 months after surgery showed that the incidence of intestinal accumulation in the pelvic floor was 9.1% (3/33) in study group and 46.4% (64/138) in control group (χ(2)=15.537, P<0.001). Conclusion: Pelvic peritoneal reconstruction using stratafix in laparoscopic anterior resection of middle and low rectal cancer is safe and feasible, which may reduce the probability of the secondary operation in patients with anastomotic leakage and significantly improve postoperative anal function.

Multicenter real-world study on safety and efficacy of neoadjuvant therapy in combination with immunotherapy for colorectal cancer / 中华胃肠外科杂志

Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.

Anterior thalamic nuclei deep brain stimulation inhibits mossy fiber sprouting via 3',5'-cyclic adenosine monophosphate/protein kinase A signaling pathway in a chronic epileptic monkey model / 中华医学杂志(英文版)

BACKGROUND@#Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.@*METHODS@#Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.@*RESULTS@#ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).@*CONCLUSION@#ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

Positive Association of Human SHC3 Gene with Schizophrenia in a Northeast Chinese Han Population

Objective@#Schizophrenia is one of the most devastating neuropsychiatric disorders. Genetic epidemiological studies have confirmed that schizophrenia is a genetic disease. Genes promoting neurodevelopment may be potential candidates for schizophrenia. As an adaptor linking a number of tyrosine kinase receptors in multiple intracellular signaling cascades, Src homology 2 domain containing transforming protein 3 (SHC3) is a member of the Shc-like adaptor protein family, and expressed predominantly in the mature neurons of the central nervous system (CNS). In the present study, we aimed to investigate the association of SHC3 and schizophrenia. @*Methods@#An independent case-control association study was performed in a sample including 710 schizophrenia patients and 1314 healthy controls from a Northeast Chinese Han population. @*Results@#The allelic and genotypic association analyses showed that four SNPs in SHC3 significantly associated with schizophrenia (rs2316280, rs4877041, rs944485 and rs7021743). The haplotype composing of these four SNPs also showed significantly individual and global association with schizophrenia. @*Conclusion@#Our present results suggest SHC3 as a susceptibility gene for schizophrenia.

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy / 中国结合医学杂志

OBJECTIVE@#To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening.@*METHODS@#The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper.@*RESULTS@#It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score.@*CONCLUSIONS@#A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy / 中国结合医学杂志

OBJECTIVE@#To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening.@*METHODS@#The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper.@*RESULTS@#It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score.@*CONCLUSIONS@#A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.

Several suggestion of operation for colorectal cancer under the outbreak of Corona Virus Disease 19 in China / 中华胃肠外科杂志

Pneumonia caused by SARS-Cov-2 infection has been reported in Wuhan since December 2019, and spread rapidly across the country. The radical operation of colorectal cancer is confine operation. Patients with colorectal cancer should receive operation as soon as possible after elective operation is resumed in each hospital. SARS-Cov-2 virus can be transmitted by asymptomatic infectors, and it has been confirmed to be transmitted by droplets and contact. However, fecal-oral transmission and aerosol transmission have not been excluded. Based onLaparoscopic colorectal operation experiences, the author suggests that the surgery strategy for colorectal cancer patients under the COVID-19 situation. Recommending laparoscopy-assisted radical surgery for colorectal cancer patients. The aerosols need to be strictly managed during operation. NOSES and TaTME should be carried out with cautious during the epidemic period. Protective stoma should be carried out scientifically and reasonably, and the protection of operating room personnel should be strengthened.

Several suggestion of operation for colorectal cancer under the outbreak of Corona Virus Disease 19 in China / 中华胃肠外科杂志

Pneumonia caused by SARS-Cov-2 infection has been reported in Wuhan since December 2019, and spread rapidly across the country. The radical operation of colorectal cancer is confine operation. Patients with colorectal cancer should receive operation as soon as possible after elective operation is resumed in each hospital. SARS-Cov-2 virus can be transmitted by asymptomatic infectors, and it has been confirmed to be transmitted by droplets and contact. However, fecal-oral transmission and aerosol transmission have not been excluded. Based onLaparoscopic colorectal operation experiences, the author suggests that the surgery strategy for colorectal cancer patients under the COVID-19 situation. Recommending laparoscopy-assisted radical surgery for colorectal cancer patients. The aerosols need to be strictly managed during operation. NOSES and TaTME should be carried out with cautious during the epidemic period. Protective stoma should be carried out scientifically and reasonably, and the protection of operating room personnel should be strengthened.

A Preliminary study on the preoperative risk score system for simultaneous operation for patients with colorectal cancer and liver metastases / 中华肝胆外科杂志

Objective:This study aims to analyze the prognosis of patients who underwent a simultaneous operations for colorectal cancer and liver metastases, and to establish a prognostic scoring system for these patients.Methods:From January 2010 to March 2019, the clinicopathological data of patients with colorectal cancer and liver metastases simultaneously operated at Shanghai Changhai Hospital were collected. The clinicopathological prognostic factors on tumor recurrence and survival outcomes on follow-up were analyzed. Single and multiple factors Cox regression analyses were used to determine the risk factors which affected the prognosis of patients. Using the risk factors of poor prognosis on Cox analysis, 1 point was given to each risk factor. Patients were then divided into different groups according to the different total scores. The median overall survival and disease-free survival of each group were analyzed.Results:Of 234 patients included in this study, there were 126 males and 108 females. The average age was (57.4±10.8) years. The median survival was 44.85 months. The 1-, 3-, and 5-year survival rates of the whole group were 87.3%, 55.2%, and 22.9%, respectively. Primary tumor in right colon, preoperative carcinoembryonic antigen ≥200 ng/ml, multiple liver metastases, and poorly differentiated adenocarcinoma/mucinous adenocarcinoma were independent risk factors of poor prognosis. After 1 point was given to each of the above 4 items, patients were then divided into the low-risk (0-1) and high-risk (2-4) groups. The median survivals of patients in the low-risk group ( n=174) and high-risk group ( n=60) were 53 months and 29 months, respectively. The corresponding median disease-free survivals were 21.34 months and 8.48 months, respectively. The differences between the 2 groups were significant ( P<0.05). Conclusion:The results of this study preliminary established a predictive scoring system for patients with simultaneous colorectal cancer and liver which can play a role in selecting treatment options for these patients.

Analysis of scientific research courses and degree courses in the teaching of eight -year program clinical medicine in China / 中华医学教育探索杂志

Since the establishment of eight-year clinical medicine specialty, in line with the princi-ple of "eight-year consistency and fusion of the bachelor and doctor degree", the training mode of "strength-ening the foundation, focusing on quality, overall optimization, facing the clinical" has been implemented. In order to reach the standard of professional doctorate, a series of courses of professional doctorate need to be fused in limited time and designed carefully by medical schools. However, grasping proper teaching time and opportunity is particularly important for students' learning and development. By collecting the courses information of 11 medical colleges and universities offering eight-year clinical medicine specialty, we have analyzed the teaching time, methods and course categories of scientific research training courses and graduate degree courses, aiming to find the appropriate teaching program.

Oligodendrocyte precursor cell transplantation in treatment of demyelinating diseases of central nervous system: Recent progress / 第二军医大学学报

Demyelinating diseases are a group of nervous system disorders characterized by myelin sheath damage. Demyelinating diseases can seriously affect the quality of life of its victims and still lack satisfying therapeutic options. Oligodendrocyte precursor cells (OPCs) are progenitor cells exist in the central nervous system (CNS), with migration and proliferation capacities and potential to differentiate into oligodendrocytes (OLs), which are myelinated cells in the CNS, indicating that OPCs are closely related to myelination and post-injury regeneration in CNS. Recently, with the improved understanding of the mechanisms of OPCs development and lineage specification, the approaches to gain functional OPCs through directed differentiation from pluripotent stem cells or lineage reprogramming from somatic cells have been greatly promoted. Based on these achievements, OPCs transplantation becomes a promising therapeutic option for the treatment of demyelinating diseases of CNS. In this review, we summarized the latest research progress in this field.

Comparison of clinicopathological features and prognosis between left-sided colon cancer and right-sided colon cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the clinicopathological features and prognosis between left-sided colon cancer (LC) and right-sided colon cancer (RC).</p><p><b>METHODS</b>Clinicopathological and follow-up data of 2 174 colon carcinoma cases undergoing resection at Shanghai Changhai Hospital of The Second Military Medical University from January 2000 to December 2010 were retrospectively analyzed. Patients with transverse colon cancer, overlapping position, unknown location, recurrent cancer, multiple primary cancer, concomitant malignant tumors, preoperative chemotherapy, local resection, incomplete clinical data and missed follow up were excluded. Finally, a total of 1 036 patients, whose primary tumors were radically removed, were enrolled, with 563 patients in LC group (including carcinoma in cecum, ascending colon and hepatic flexure) and 473 in RC group (including carcinoma in splenic flexure, descending colon and sigmoid colon). The clinicopathological features and survival, including median overall survival, 5-year overall survival rate, tumor specific median overall survival, cancer specific 5-year overall survival rate, were compared between LC and RC groups. Tumor specific overall survival was defined as the period between operation date to the date of death caused by cancer progression. Multivariate Cox regression analysis was used to analyze the influencing factors of survival. Propensity score matching was carried out to balance the clinicopathological factors between the two groups with the SAS 9.3, taking the following parameters into consideration (age, gender, gross appearance, tumor diameter, invasion depth, lymph node metastasis, distant metastasis, TNM stages, differentiation, CEA and CA199-9). Patients in RC group and LC group were matched according to the propensity scores and the clinicopathological characteristics and prognosis of two groups were compared again.</p><p><b>RESULTS</b>No significant differences were identified between the two groups in age, distant metastasis and serum CEA level. Compared with RC group, LC group had more male patients [60.9%(343/563) vs. 51.0%(241/473), P=0.001], more ulcerative tumors [71.9% (405/563) vs. 65.3%(309/473), P=0.006], better differentiation [well/moderately differentiated: 87.5%(493/563) vs. 73.8%(349/473), P=0.000], lower infiltration depth [T1-2: 17.1%(96/563) vs. 10.1%(48/473), P=0.001], higher lymph node metastasis rate [N0: 53.3%(300/563) vs. 62.4%(295/473), P=0.013], lower TNM stage [stage I(: 13.3%(75/563) vs. 7.8%(37/473), P=0.000], lower serum CA199 level [<37 kU/L: 68.4% (385/563) vs. 62.6% (296/473), P=0.022] and smaller tumor diameter [<5.0 cm: 55.1%(310/563) vs. 38.3%(181/473), P=0.000]. The median overall survival was 82 months and 76 months in LC and RC groups, respectively, and the 5-year overall survival rate was 58.3% and 50.9%(P=0.038). The median tumor specific survival was 84 months and 78 months in LC and RC groups, respectively, and the 5-year tumor specific overall survival rate was 60.6% and 52.9% (P=0.031). Multivariate Cox regression analysis showed that tumor location (LC vs. RC) was not associated with overall survival (P=0.106) and tumor specific survival (P=0.091). After propensity score matching, no significant difference was found in clinicopathological factors and propensity score (0.458±0.129 vs. 0.459±0.129, P=0.622) between LC and RC group. After matching, there was no significant difference in overall survival rate (54.0% vs. 51.7%, P=0.982) and tumor specific overall survival rate(56.4% vs. 53.1%, P=0.819) between two groups.</p><p><b>CONCLUSION</b>Significant difference exists between RC and LC in clinicopathological factors, but not in survival.</p>

Design and implementation of sitting posture fixation device for baby hip ultrasonic screening / 医疗卫生装备

Objective To design a sitting posture fixation device for the ultrasonic imaging of baby hip joint dysplasia.Methods The device was composed of a riser,a fixation base,No.1 holding plate,No.2 holding plate,a baby fixation plate and two detection windows.The two holding plates made the baby's spine and femurs form a right angle at the sitting posture,so that the standard posture was obtained for hip joint ultrasonic imaging.The detection windows facilitated to gain the optimal image for the both sides of the hip joint.Results The device contributed to acquiring baby hip joint image rapidly with high quality and decreased examination time.Conclusion The device can be used for the massive screening of developmental hip joint abnormality.