Research progress in the treatment of Alzheimer's disease by regulating brain-gut-microbiome axis with "Sanjiao" acupuncture method / 中华老年医学杂志

Recent studies have found that the brain-gut-microbiome axis(BGMA)is closely related to the occurrence and development of Alzheimer's disease(AD). BGMA can affect AD in various aspects such as neuro-immune regulation and intestinal microflora, and is a potential new target for the treatment of AD.The "Sanjiao" acupuncture method is proposed by professor Han Jingxian, a famous Chinese medicine practitioner, based on his theory of "dysfunction of Qi activity of Sanjiao leads to aging" , and has been widely used in the treatment of AD and other age-related diseases in clinical practice.This article reviews the theory of "dysfunction of Qi activity of Sanjiao leads to aging" and the relationship between the "Sanjiao" acupuncture method and BGMA, with the hope that the "San Jiao" acupuncture method can become a new target for treatment of AD in the future.

Discovery of a highly potent and orally available importin-β1 inhibitor that overcomes enzalutamide-resistance in advanced prostate cancer

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Effects and related mechanisms of histone deacetylase inhibitors on the proliferation of choroidal melanoma C918 cell line / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To elucidate the effect of histone deacetylase(HDAC)inhibitor suberoylanilide hydroxamic acid(SAHA)on the proliferation of choroidal melanoma(CM)cell line C918 and to explore the related mechanism.METHODS: Inverted fluorescence microscope was used to observe the effect of different concentrations of SAHA(0.625, 1.25 or 2.5 μmol/L)on the morphology of C918 cell. The cell viability was detected by cholecystokinin octapeptide(CCK-8)assay. Plate clone formation assay and EdU staining were carried out to measure the effect of SAHA on the cell proliferation. Meanwhile, the expressions of cell proliferation-related proteins including c-Myc, CyclinA2 and CDK2, and histone deacetylase 7(HDAC7)and fibroblast growth factor 18(FGF18)were detected by Western blot.RESULTS: Compared with the control group, the cell density was reduced in SAHA. SAHA could also promote cell shrinkage, and the inhibition on cell was in a concentration-dependent manner. CCK-8 assay showed that SAHA treatment decreased cell viability in a dose-dependent manner and the inhibition rate was 80% when SAHA at 2.5 μmol/L. Compared with the control group, Western blot showed that SAHA could suppress the expression of cell proliferation proteins including c-Myc, CyclinA2 and CDK2 in a dose-dependent manner. In addition, 1.25 μmol/L SAHA significantly decreased the numbers of EdU staining positive cells and cell clones. More importantly, SAHA could dose-dependently decrease the expression of HDAC7 and FGF18 compared with control group.CONCLUSION: SAHA could inhibit the proliferation of CM cell line C918 by inhibiting the HDAC7/FGF18 signaling pathway.

Collateral Flow in Magnetic Resonance Angiography:Prognostic Value for Vertebrobasilar Stenosis With Stroke Recurrence

Background@#and Purpose Intracranial vertebrobasilar atherosclerotic stenosis (IVBAS) is a major cause of posterior circulation stroke. Some patients suffer from stroke recurrence despite receiving medical treatment. This study aimed to determine the prognostic value of a new score for the posterior communicating artery and the P1 segment of the posterior cerebral artery (PCoA-P1) for predicting stroke recurrence in IVBAS. @*Methods@#We retrospectively enrolled patients with severe IVBAS (70%–99%). According to the number of stroke recurrences, patients were divided into no-recurrence, single-recurrence, and multiple-recurrences groups. We developed a new 5-point grading scale, with the PCoA-P1 score ranging from 0 to 4 based on magnetic resonance angiography, in which primary collaterals were dichotomized into good (2–4 points) and poor (0 or 1 point). Stroke recurrences after the index stroke were recorded. Patients who did not experience stroke recurrence were compared with those who experienced single or multiple stroke recurrences. @*Results@#From January 2012 to December 2019, 176 patients were enrolled, of which 116 (65.9%) had no stroke recurrence, 35 (19.9%) had a single stroke recurrence, and 25 (14.2%) had multiple stroke recurrences. Patients with single stroke recurrence (odds ratio [OR]= 4.134, 95% confidence interval [CI]=1.822–9.380, p=0.001) and multiple stroke recurrences (OR=6.894, 95% CI=2.489–19.092, p<0.001) were more likely to have poor primary collaterals than those with no stroke recurrence. @*Conclusions@#The new PCoA-P1 score appears to provide improve predictions of stroke recurrence in patients with IVBAS.

Post-marketing immunogenicity and safety of domestic 23-valent pneumococcal polysaccharide vaccine: a multicenter study / 中华微生物学和免疫学杂志

Objective:To evaluate the post-marketing safety and immunogenicity of a 23-valent pneumococcal polysaccharide vaccine (PPV23).Methods:From September 2020 to June 2021, a clinical trial of single-dose PPV23 was conducted in people ≥3 years old in Centers for Disease Control and Prevention of Guizhou, Hunan and Fujian provinces. Blood samples were collects from the subjects before and 30 d after vaccination. ELISA was used to quantitatively detect IgG antibodies against capsular polysaccharides of 23 Streptococcus pneumoniae serotypes in serum samples. The adverse events (AEs) were monitored within 7 d after vaccination. Results:A total of 409 subjects were enrolled and included in safety analysis. Except for one with antibody level inversion, the other 408 participants were included in immunogenicity analysis. The levels of antibodies against the 23 Streptococcus pneumoniae serotypes were all increased after vaccination by an average of 4.24 folds. The two-fold growth rates of the antibodies ranged from 51.72% to 96.81% with a total two-fold growth rate of 78.59%. The overall rate of AEs was 27.14% (111/409). Local AEs were mainly pain, induration, redness and swollen. No serious adverse events related to vaccination occurred. Conclusions:This study preliminarily demonstrated the good immunogenicity and safety of PPV23 vaccine.

Effects of daphresin on synovial fibroblasts in rheumatoid arthritis based on PERK/ATF4/CHOP signaling pathway / 中国药理学通报

Aim To investigate the effects of DAP on human rheumatoid arthritis synovial fibroblasts(RA-FLS)and its relationship with endoplasmic reticulum stress(ERS)PERK/ATF4/CHOP signaling pathway.Methods RA-FLS cells were cultured and identified by immunofluorescence assay for Vimentin and CD68.CCK-8 detected(0,5,10,20,30,40,50,60,70)mg·L-1 DAP on the proliferation activity of RA-FLS cells.According to the proliferation activity,the experiment was divided into blank group(Blank),low dose group(L-DAP),medium dose group(M-DAP),high dose group(H-DAP)and high dose+specific inhibitor 4-PBA group(H-DAP+4-PBA).The levels of TNF-α and IL-6 were detected by ELISA.Cell apoptosis was detected by flow cytometry.The invasion and migration of cells were detected by Transwell and scratches assays,and the expressions of endoplasmic reticulum stress-related proteins GRP78,PERK,P-PERK,ATF4,CHOP,Caspase-12,C-Caspase-12 and Bcl-2 were assessed by Western blot.Results CCK-8 results showed that compared with 0 mg·L-1 DAP group,the proliferation activity of each group in 20-70 mg·L-1 DAP group was significantly different(P<0.05),and the proliferation rate corresponding to 0,20,40 and 60 mg·L-1 DAP group was significantly different(P<0.05).This concentration was used as the basis for blank,low-dose,medium-dose,high-dose groups and high-dose+4-PBA experimental grouping.DAP could inhibit the release of inflammatory cytokines IL-6 and TNF-α from RA-FLS cells in concentration,reduce the invasion ability of cells,promote apoptosis,upregulate the expression of PERK,P-PERK,ATF4,GRP78,CHOP,Caspase-12, C-caspase-12 proteins and decrease the expression level of anti-apoptotic protein Bcl-2.Another set of experiments demonstrated that high dose DAP+4-PBA could up-regulate the expression of IL-6 and TNF-α,as well as the invasion of cells,and inhibit the expression of apoptosis and ERs-related proteins.Conclusions Daphresin regulates the secretion of inflammatory factors by activating the PERK/ATF4/CHOP signaling pathway,inhibits the proliferation and invasion of RA-FLS cells,and induces apoptosis,which is expected to be a potential therapeutic pathway for RA.

Comparative analysis of work-related musculoskeletal disorders catalogues / 中华劳动卫生职业病杂志

Work-related musculoskeletal disorders (WMSDs) refer to musculoskeletal disorders caused by work or work as the main cause, which are characterized by high prevalence and heavy burden of disease as a global problem. The classification and catalog of occupational diseases is of great significance for guiding the prevention and control of occupational diseases and safeguarding the rights and interests of workers. The types of WMSDs included in the list of occupational diseases vary greatly from country to country, and the regulations on specific pathogenic factors are also inconsistent. By sorting out and analyzing the lists and characteristics of WMSDs at home and abroad, and using the International Statistical Classification of Diseases and Related Health Problems (ICD-10) in occupational health to standardize of WMSDs in various countries, which would lay the foundation for future multi-country WMSDs occupational health registration and disease burden research, and provide a reference for China to revise the WMSDs list.

Relationship between pesticide exposure and lipid metabolism in population / 中华劳动卫生职业病杂志

Objective: To investigate the effect of pesticides and herbicides on lipid metabolism. Methods: In November 2020, Based on the data of the national health and Nutrition Survey (NHANES) (2011-2014) , select the population aged 20~65 who have demographic information, pesticide use and data of four lipid metabolism indicators [total cholesterol (TC) , triglyceride (TG) , high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) ] (n=3039) . The subjects were divided into insecticide group (320 people) and non insecticide group (2719) according to the use of insecticides, and herbicide group (156 people) and non herbicide group according to the use of herbicides. Results: Among the 3039 subjects, the males and female were 1509 (49.7%) and 1530 (50.3%) respectively. The males age was (39.7±12.0) years and the females age was (40.2±12.0) years The concentration of HDLC in the NHANES (55.4±15.0) mg/dl was lower than that of (58.2±14.2) mg/dL in the non herbicide group (P<0.05) (b=-0.044, P<0.05) . The results showed that the use of herbicides was related to the decrease of HDLC and the increase of LDLC and LDLC/HDLC in female population (b=-0.050, 0.062, 0.067, all P<0.05) . Conclusion: Herbicide exposure can cause the change of lipid metabolism, and the effect on female population is more obvious.

One case of bloodstream infection caused by Ureaplasma urealyticum / 中国热带医学

@#Abstract: Objective To analyze a case of bloodstream infection caused by Ureaplasma urealyticum after abortion in Anxi County Hospital, so as to provide basis for the clinical diagnosis and treatment. Methods　The diagnosis of Ureaplasma urealyticum in this patient with bloodstream infection was retrospectively analyzed. The basic clinical data and laboratory diagnosis data were collected, including the characteristics of blood culture curve, Wright staining of culture medium, drug sensitivity of Mycoplasma liquid identification, colony characteristics of solid medium, and the conclusion of targeted DNA sequencing. Through the comprehensive analysis of the above data, the rapid diagnosis of this case can be realized by optimizing the detection and diagnosis process. Results　The clinical manifestations of this patient were fever of 38.5 ℃, CRP:14.85 mg/L, WBC:14.33×109/L, NET: 85.40%, PCT: 0.12 ng/mL, IL-6: 665.6 pg/mL, positive after 3 days of blood culture, no bacteria were found in Gram stain, and sand-like purple bacteria were observed after adding Wright's stain. After inoculation in blood agar, Mycoplasma solid and liquid medium, no colonies were grown in blood agar, after 48 h and 5 d. On Mycoplasma A7 agar, the edge of brown fried egg colony was striature, and it could be identified as Ureaplasma urealyticum with the Mycoplasma ID & AST panel, which was resistant to quinolones and spectinomycin, but sensitive to macrolides, tetracyclines and lincomycin. Subsequent targeted DNA sequencing results were also confirmed for Ureaplasma urealyticum. Before receiving the report, clinical experience treatment with ceftriaxone metronidazole was used to fight infection with negative bacilli and anaerobic bacteria. Mycoplasma was not treated with targeted treatment. After 3 days, the patient's body temperature returned to normal, inflammation index decreased, and the patient asked to be discharged. Conclusions　At present, there are few reports of bloodstream infection caused by Ureaplasma urealyticum, and the lack of clinical understanding can easily lead to misdiagnosis and missed diagnosis. In order to improve the detection rate of Mycoplasma in blood culture, it is necessary to optimize the detection procedure of blood culture and provide accurate diagnosis and treatment basis for clinical practice. However, it is clear from this case that Mycoplasma bloodstream infection cases are self-limited infection and can recover by themselves without targeted treatment in patients with normal immunity. Therefore, it is very important to protect the immunity of patients.

Preliminary evaluation on the efficacy of emergency transcatheter aortic valve replacement: a multicenter study / 中华心血管病杂志

Objectives: To explore the efficacy and safety of emergency transcatheter aortic valve replacement (TAVR). Methods: Data of patients who underwent emergency TAVR in eight centers, namely Fuwai Hospital, Wuhan Asia Heart Hospital, Xijing Hospital, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Guangdong Provincial People's Hospital, Zhongshan Hospital Affiliated to Fudan University, the First Affiliated Hospital of Zhengzhou University, the Second Xiangya Hospital of Central South University, between May 2017 and December 2020 were retrospectively analyzed. The use of mechanical circulatory support system (MCS) and the results of laboratory tests (N-terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography (mean aortic valve cross valve pressure difference and left ventricular ejection fraction) before and after operation were collected. The primary endpoint was all-cause death, and the secondary endpoints were stroke, major bleeding, major vascular complications, myocardial infarction, permanent pacemaker implantation, and acute renal injury. Device success was caculated, which refered to absence of procedural mortality and correct positioning of a single prosthetic heart valve into the proper anatomical location and intended performance of the prosthetic heart valve (mean aortic valve gradient<20 mmHg(1 mmHg=0.133 kPa) or peak velocity<3 m/s, with no moderate or severe prosthetic valve regurgitation). Kaplan-Meier survival curve was used to estimate the survival rate of patients during follow-up. Results: This study included 48 patients. The age was (72.5±8.1) years, and 34 patients were males (70.8%). Device success rate was 91.7% (44/48). The mean aortic valve transvalvular pressure was significantly decreased after operation ((12.3±6.4)mmHg vs. (60.2±23.8)mmHg, P<0.000 1). Left ventricular ejection fraction was significantly increased ((41.5±11.7)% vs. (31.0±11.3)%, P<0.000 1). NT-proBNP significantly decreased (3 492.0 (1 638.8, 7 165.5) ng/L vs. 12 418.5 (6 693.8, 35 000.0) ng/L, P<0.000 1). In-hospital all-cause mortality was 8.3% (4/48). During hospitalization, the rate of stroke was 2.1% (1/48), major bleeding was 6.3% (3/48), major vascular complications was 10.4% (5/48), myocardial infarction was 4.2% (2/48), permanent pacemaker implantation was 6.3% (3/48), and the rate of acute renal injury was 12.5% (6/48). MCS was used in 20 patients (41.7%). The median follow-up time was 196 days. During the follow-up, one patient died (due to systemic metastasis of pancreatic cancer), two cases suffered new myocardial infarction and one case received permanent pacemaker implantation. The survival rate of 30 days, 1 year and 2 years after the operation were 91.7% (44/48), 89.6% (43/48), 89.6% (43/48), respectively. Conclusion: Emergency TAVR may be a safe and effective treatment for patients with severe decompensated aortic valve stenosis.

Effect of Aqueous Extract of Trametes robiniophila on Proliferation of Human Prostate Cancer VCaP Cells / 中国实验方剂学杂志

ObjectiveTo investigate effect of aqueous extract of Trametes robiniophila （TRM，Huaier） on autophagy of human prostate cancer VCaP cells and Lamin B1 expression， so as to uncover its role in the proliferation of VCaP cells. MethodThe inhibitory effect of 0， 2， 4， 6， 8， 10 g·L-1 TRM aqueous extract on the proliferation of human prostate cancer VCaP cells at different time points were determined by cell counting kit-8 （CCK-8） assay. Acridine orange staining was conducted for analyzing the effect of TRM aqueous extract on the formation of autolysosomes in VCaP cells. After medication， the expression of microtubule-associated protein Ⅰ light chain 3 （LC3）， autophagy-related protein 3 （Atg3）， autophagy-related protein 5 （Atg5）， and autophagy-related protein 7 （Atg7） in VCaP cells were detected by Western blot. The effect of TRM aqueous extract alone and its combination with autophagy inhibitor bafilomycin A1 on the proliferation of VCaP cells were assayed by CCK-8 assay. RNA interference technology was used to explore the role of Lamin B1 in anti-proliferation of VCaP cells by TRM. ResultCompared with the blank group， TRM aqueous extract inhibited the proliferation of human prostate cancer VCaP cells in a time- and concentration-dependent manner （P<0.01）. Acridine orange staining showed that TRM aqueous extract promoted the formation of autolysosomes in VCaP cells. As revealed by Western blotting， TRM aqueous extract up-regulated the expression levels of LC3-Ⅱ， Atg3， Atg5， and Atg7 in contrast to those in the blank group （P<0.05）. All these indicated that TRM aqueous extract induced the autophagy of VCaP cells. In addition， autophagy inhibition impaired the sensitivity of VCaP cells to TRM aqueous extract （P<0.05）. The comparison with the blank group showed that TRM aqueous extract inhibited Lamin B1 protein expression in VCaP cells （P<0.01）， which in turns weakened the sensitivity of VCaP cells to TRM aqueous extract. ConclusionTRM aqueous extract inhibited the proliferation of human prostate cancer VCaP cells possibly by inducing autography and down-regulating Lamin B1 expression. This study has provided a theoretical basis for the clinical application of TRM.

A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Application value of Clavien-Dindo classification in evaluation of postoperative short-term complications of Da Vinci robotic-assisted or laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy / 中华消化外科杂志

Objective:To investigate the application value of Clavien-Dindo classification in evaluation of postoperative short-term complications of Da Vinci robotic-assisted or laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy. Methods:The retrospective cohort study was conducted. The clinicopathological data of 262 patients with gastric cancer who were admitted to the 940th Hospital of Joint Logistic Support Force of Chinese People′s Liberation Army from January 2016 to January 2019 were collected. There were 214 males and 48 females, aged (58±11) years, with a range from 17 to 81 years. Of 262 patients, 120 cases undergoing Da Vinci robotic-assisted total gastrectomy + D 2 lymphadenectomy + Roux-en-Y anastomosis were divided into robotic group, and 142 cases undergoing laparoscopic-assisted total gastrectomy + D 2 lymphadenectomy + Roux-en-Y anastomosis were divided into laparoscopic group. Observation indicators: (1) intraoperative and postoperative situations; (2) postoperative pathological examination; (3)complications; (4) stratified analysis; (5) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect complications, tumor recurrence and survival of patients within postoperative 2 months. The follow-up was up to May 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ranked data between groups was analyzed using the rank sum test. Results:(1) Intraoperative and postoperative situations: cases undergoing conversion to open surgery, the operation time, volume of intraoperative blood loss, the number of lymph node dissected, time to first flatus, time to initial fluid diet intake, duration of postoperative hospital stay of the robotic group were 1, (243±42)minutes, 100 mL(range, 100-150 mL), 38±15, (2.8±1.0)days, 3 days(range, 3-4 days), 11 days(range, 9-13 days), respectively. The above indicators of the laparoscopic group were 2, (244±38)minutes, 100 mL(range, 100-150 mL), 34±14, (3.2±1.0)days, 4 days(range, 3-5 days), 10 days(range, 9-13 days), respectively. There were significant differences in the number of lymph node dissected, time to first flatus, time to initial fluid diet intake between the two groups ( t=2.068, -3.030, Z=-3.370, P<0.05), and there was no significant difference in cases undergoing conversion to open surgery, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay between the two groups ( χ2=0.000, t=-0.158, Z=-1.824, -0.088, P>0.05). (2) Postoperative pathological examination: cases with well differentiated tumor, moderately differentiated tumor, poorly differentiated tumor, signet ring cell carcinoma or other types of tumor, cases in stage T1b, T2, T3 or T4a (pT staging), cases in stage N0, N1, N2, N3a or N3b (pN staging), cases in stage ⅠB, ⅡA, ⅡB, ⅢA, ⅢB or ⅢC (pTNM staging) of the robotic group were 6, 50, 55, 9, 10, 22, 63, 25, 42, 19, 19, 24, 16, 17, 22, 23, 20, 23, 15, respectively. The above indicators of the laparoscopic group were 4, 42, 84, 12, 6, 18, 81, 37, 39, 27, 32, 19, 25, 13, 19, 28, 39, 16, 27, respectively. There was no significant difference in the above indicators between the two groups ( Z=-1.880, -1.827, -0.140, -1.460, P>0.05). (3) Complications: cases with complication classified as grade Ⅰ, grade Ⅱ, grade Ⅲa, grade Ⅲb, grade Ⅳa, grade Ⅳb of Clavien-Dindo classification, cases with death, cases with overall complications, cases with severe complications of the robotic group were 9, 6, 3, 2, 2, 0, 0, 22, 7, respectively. The above indicators of the laparoscopic group were 12, 15, 9, 6, 3, 1, 1, 47, 20, respectively. There were significant differences in cases with overall complications, cases with severe complications between the two groups ( χ2=7.309, 4.790, P<0.05), and there was no significant difference in cases with complication classified as grade Ⅰ, grade Ⅱ, grade Ⅲa, grade Ⅲb, grade Ⅳa, grade Ⅳb of Clavien-Dindo classification, cases with death between the two groups ( χ2=0.080, 2.730, 1.042, 0.704, 0.000, 0.000, 0.000, P>0.05). (4) Stratified analysis: of the patients with overall complications in robotic group, cases of male or female, cases aged ≥65 years or <65 years, cases with body mass index (BMI) ≥24 kg/m 2 or <24 kg/m 2, cases with tumor diameter ≥5 cm or <5 cm, cases with or without abdominal surgery, cases with tumor located at upper stomach or middle stomach, cases in Ⅰ-Ⅱ grade or Ⅲ grade of American Society of Anesthesiologists (ASA) classification, cases with well differentiated tumor or undifferentiated tumor, cases in stage Ⅰ-Ⅱ or stage Ⅲ (pTNM staging), cases with operation time ≥250 minutes or <250 minutes, cases with volume of intraoperative blood loss ≥150 mL or <150 mL, cases with the number of lymph node dissected ≥25 or <25 were 15, 7, 14, 8, 11, 11, 16, 6, 4, 18, 19, 3, 15, 7, 7, 15, 8, 14, 12, 10, 12, 10, 14, 8, respectively. The above indicators of patients with overall complications in the laparoscopic group were 33, 14, 17, 30, 16, 31, 36, 11, 11, 36, 27, 20, 31, 16, 13, 34, 14, 33, 24, 23, respectively. Of the patients with overall complication, there were significant differences in cases of male, cases aged ≥65 years or <65 years, cases with BMI<24 kg/m 2, cases with tumor diameter≥5 cm, cases without abdominal surgery, cases with tumor located at middle stomach, cases in Ⅰ-Ⅱ grade or Ⅲ grade of ASA classification, cases with well differentiated tumor, cases in stage Ⅲ (pTNM staging), cases with operation time ≥250 minutes, cases with volume of intraoperative blood loss <150 mL, cases with the number of lymph node dissected ≥25 between the two groups ( χ2=6.683, 4.207, 6.761, 7.438, 4.297, 6.325, 9.433, 3.970, 4.850, 4.911, 3.952, 3.915, 6.865, 4.128, P<0.05) and there was no significant difference in cases of female, cases with BMI≥24 kg/m 2, cases with tumor diameter <5 cm, cases with abdominal surgery, cases with tumor located at upper stomach, cases with undifferentiated tumor, cases in stage Ⅰ-Ⅱ (pTNM staging), cases with operation time < 250 minutes, cases with volume of intraoperative blood loss ≥150 mL, cases with the number of lymph node dissected <25 between the two groups ( χ2=0.277, 1.052, 1.996, 1.552, 2.172, 2.594, 2.244, 3.771, 1.627, 3.223, P>0.05). (5) Follow-up: 262 patients were followed up postoperatively for 2 months. During the follow-up, no patient was diagnosed with tumor recurrence, and one patient in the laparoscopic group died of severe infection. Conclusions:The Clavien-Dindo classification can be used in evaluating postoperative short-term complications of Da Vinci robotic-assisted or laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy. Compared with laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy, Da Vinci robotic-assisted total gastrectomy with D 2 lymphadenectomy has the advantages of minimally invasiveness, low incidence of overall and severe complication.

Influence of oxidative/antioxidative biomarkers and inflammatory cytokines on rats after sub-acute orally administration of titanium dioxide nanoparticles / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the sub-acute oral effect of titanium dioxide (TiO2) nanoparticles on the oxidation/antioxidation biomarkers and inflammatory cytokines in blood, liver, intestine, and colon in rats.@*METHODS@#Twenty four 4-week-old clean-grade Sprague Dawley (SD) rats were randomly devided into 4 groups by body weight (n=6, control, low, middle, and high), in which the rats were orally exposed to TiO2 nanoparticles at doses of 0, 2, 10 and 50 mg/kg body weight/day for 28 consecutive days separately. Food intake, body weight and abnormal behaviors during the experiment were recorded. The rats were euthanized on the 29th day. The blood was collected via abdominal aortic method and centrifuged to collect the serum. Tissues from liver, intestine and colon were collected and homogenated. Then enzyme-linked immunosorbent assay (ELISA) and microwell plate methods were used to detect oxidation/antioxidation biomarkers including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total mercapto (T-SH), glutathione disulfide (GSSG), malomdialdehvde (MDA) and inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the serum, liver, intestine and colon in the rats.@*RESULTS@#Compared with the control group, no significant differences in body weight, food intake and organ coefficients were observed in all the three groups after TiO2 gavage. No significant changes in GSH, GSH-Px, T-SH, and IL-6 were observed. Compared with the control group, significant increase of SOD activity in serum in high dose group, signi-ficant increase of GSSG concentration in intestine in middle and high dose group and significant increase of MDA concentration in liver in low and high dose group were observed. Compared with the control group, a significant increase of TNF-α in liver in middle and high dose group was observed.@*CONCLUSION@#TiO2 nanoparticle can increase antioxidant enzymes activities in blood, increase oxidative biomarkers in liver and intestine, increase inflammatory cytokines in liver in rats after a 28-day sub-acute orally administration. Among blood, liver, intestine, and colon, liver is most sensitive to the toxicity induced by TiO2 nanoparticles, followed by intestine, blood, and colon in sequence.

Expression of Tim-3 on natural killer cells in patients with acute myeloid leukemia and its clinical significance / 中华血液学杂志

Objective: To investigate the expression characteristics of Tim-3 on natural killer (NK) cells of peripheral blood in patients with acute myeloid leukemia (AML) and its clinical significance. Methods: Peripheral blood was obtained from 39 patients with newly diagnosed AML before intervention, with peripheral blood from 28 cases of healthy volunteers collected as normal control. Using CD3, CD56 and Tim-3 as markers, expression levels of Tim-3 on the peripheral blood NK cells were detected by immune fluorescence labeling and flow cytometry. Results: The ratio of the peripheral blood CD3(-)CD56(+) NK cells in newly diagnosed AML patients (5.74±5.31) %decreased significantly, compared with the normal control (12.55±6.33) % (t=4.596, P<0.001) . Tim-3 expression on the peripheral blood NK cells in newly diagnosed AML patients (42.67±19.08) % decreased significantly, compared with the normal control group (60.99±20.69) % (t=3.781, P<0.001) . CD3(-)CD56(+)NK cell ratio of peripheral blood in AML patients was significantly correlated with Chromosome karyotype (t=2.915, P<0.005) . Expression level of Tim-3 on NK cells in the peripheral blood of AML patients had significant correlation with ratio of CR and NCCN high risk group (P<0.05) . Conclusion: The rate of NK cells in peripheral blood and the expression level of Tim-3 on NK cells in AML patients decreased significantly.The lower expression level of Tim-3 on NK cells correlate with prognosis of AML.

Diagnostic value of magnetic resonance multimode functional imaging in small hepatocellular carcinoma / 新乡医学院学报

Objective To investigate the magnetic resonance multimodal function imaging characteristics of small hepa-tocellular carcinoma and evaluate its diagnostic value in small liver cancer. Methods Thirty-nine patients with small hepato-cellular carcinoma were selected in the First Affiliated Hospital of Xinxiang Medical University from January 2016 to January 2018. The magnetic resonance plain scan data,dynamic enhance data and diffusion imaging data of all patients were analyzed. Results Forty-five lesions were found by plain scan,and 48 lesions(37 lesions were rapid rise and rapid descent type,6 le-sions were flatbed type,3 lesions were slow ascent and rapid descent type,2 lesions were not obvious strengthening type)were found by dynamic enhancement. The lesions were hyperintense or slightly hyperintense on the diffusion weighted imaging (DWI)image. The lesions were hyperintense or slightly hyperintense on the DWI. The main shape of lesions was round,irregu-lar ring and nodositas. The apparent diffusion coefficient(ADC)value of cancer tissue and normal liver tissue gradually de-creased with the increase of b value. Under the same b value,the ADC values of small hepatocellular carcinoma was significant-ly lower than that in the normal liver tissue(P < 0. 05). Conclusion Magnetic resonance multimodality functional imaging (magnetic resonance imaging dynamic enhanced combine with multi-b value DWI)can effectively improve the diagnostic effi-cacy of small hepatocellular carcinoma.

Using multi-variable grey model optimized by differential evolution algorithm to forecast plasma concentration of propofol / 药学学报

Due to the characteristics of propofol of high time-varying, and complex compartment model, the traditional method of nonlinear mixed effects modeling (NONMEM) has miscellaneous of variables and plenty of artificial factors in the estimation of propofol. This study was aimed to build a propofol prediction model based on the differential evolution (DE) algorithm and grey model. DE was used to optimize the pa-rameter of multi-variable grey model (MGM) and to build a model of prediction of the plasma concentration of propofol based on the grey model. It was compared with the results of NONMEM algorithm. In conclusion, the median performance error (MDPE) of DE-MGM was -4.6%, while the result of NONMEM is -12.13%. The median absolute performance error (MDAPE) of GA-BP neural network is 13.19%, while that of NONMEM is 23.12%. The experimental results suggest that the new method is suitable to determine the short half-life of anesthesia drug propofol with higher accuracy.

Development of buckle tourniquet with timing function / 医疗卫生装备

Objective To develop a buckle tourniquet to facilitate further casualty treatment.Methods The requirements oftheater/field first aid of the PLA were analyzed.The existing spinning tourniquet was modified from the aspects of shorteningoperation time,controlling hemostatic pressure precisely,relieving tourniquet timely etc.The developed tourniquet was madeof engineering plastics and polyester webbing,and composed of a micro-regulation buckle,a main strap,a tightening band,atimer,a garrote,Velcro,a self-adhesive band,a garrote fixation clamp etc.Results The tourniquet had the operation timebeing 11.52 s,and avoided ischemic necrosis of tissues by automatic alarm in case of 1-h hemostasis for upper limbs or 1.5-hhemostasis for lower limbers.Conclusion The tourniquet gains advantages in low cost,high portability,easy operation,high efficiency and timing function,and thus meets the requirements for theater/field first aid.

Expression of USP10 in colorectal adenocarcinoma and analysis of bioinformatics / 临床与实验病理学杂志

Purpose To investigate the expression and significance of USP10 protein and mRNA in normal colorectal mucosa and colorectal adenocarcinoma,and to analyze the cause of the disorder.Methods 99 cases of colorectal adenocarcinoma and 83 cases of normal intestinal mucosa tissue were selected.Using tissue microarray and immunohistochemistry the expression of USP10 protein was detected,and the relationship was analyzed between USP10 protein and clinical pathological parameters or prognosis survival time.The expression of USP10 mRNA was analyzed by GEO datesets.Some miRNAs that down-regulate the expression of USP10 protein were screened by bioinformatics methods.The expression of USP10 protein and miR-149 in colorectal cancer cell lines were detected by Western blot and real-time quantitative PCR.Results The positive rate of USP10 protein in normal intestinal mucosa tissues was 71.08％(59/83),which was significantly higher than that in colorectal adenocarcinoma tissues (53.54％,53/99,P =0.015).No correlation were proved between USP10 protein expression and clinical pathological parameters or survival time (P ＞ 0.05).The expression level of USP10 mRNA in colorectal adenocarcinoma was 1.07 ～ 1.45 times that were higher than that of normal intestinal mucosa,which showed that the down-regulation of USP10 protein was at the post-transcriptional level.The program predicted a putative highly-conserved binding site in the USP10 mRNA 3'UTR for miR-149 which was up regulated in colorectal adenocarcinoma tissues.In addition,the expression of miR-149 was negatively correlated with the expression of USP10 protein in colorectal cancer cell lines.Conclusion The down-regulation of USP10 protein which occurs at the post-transcriptional level is closely related to the pathogenesis of colorectal adenocarcinoma.The high expression of miR-149 may be one of the factors that negatively regulate the expression of USP10 protein.

Clinical Study of Yang Xue Rou Gan Needling in Treating Post-stroke Depression / 上海针灸杂志

Objective To evaluate the clinical efficacy of Yang Xue Rou Gan (blood-nourishing and liver-soothing) needling method in treating post-stroke depression. Method A total of 150 patients with post-stroke depression were divided into an observation group and a control group by using the random number table, 75 cases each. In addition to the same basic treatment, the control group was intervened by Fluoxetine hydrochloride, while the observation group received Yang Xue Rou Gan needling method, twice every day, 6 d as a course at 1-day interval, for 4 weeks in total. Before and after the intervention, 24-item Hamilton Depression Scale (HAMD), Modified Edinburgh-Scandinavian Stroke Scale (MESSS), and activities of daily living [ADL, Barthel Index (BI)] were evaluated. Result After the intervention, HAMD, MESSS, and BI scores were significantly changed in both groups (P<0.05), indicating that the two groups both had improvements in depression symptoms and signs; there were significant differences between the two groups (P<0.01), suggesting that the observation group had a more significant efficacy in treating depression. Conclusion Yang Xue Rou Gan needling method can notably improve the depression and neural deficit level in post-stroke depression patients.