Objective:To evaluate the long-term outcomes and prognostic factors of locally advanced gastric cancer with serosa-invasion.Methods:This study is a retrospective cohort study. The clinical and pathological data of 495 patients with locally advanced gastric cancer with serosa-invasion who underwent laparoscopic radical gastrectomy in Department of General Surgery, the First Hospital Affiliated to Army Medical University from October 2012 to October 2018 was analyzed retrospectively. There were 356 males and 139 females with an age ( M(IQR)) of 59 (16) years (range: 18 to 75 years). Observation indicators included postoperative results and long-term prognosis. The survival curve was drawn by the Kaplan-Meier method. Univariate and multivariate prognostic analysis was performed using the Cox proportional hazards model. Results:Among the 495 patients, a total of 57 patients (11.5%) were lost to follow-up, with a follow-up time of 89 (40) months (range: 23 to 134 months). The 5-year disease-free survival rate (DFS) and the 5-year overall survival rate (OS) were 56.0% and 58.2%, respectively. The 5-year DFS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 60.5%, 51.6%, 33.3%, respectively. The 5-year OS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 62.2%, 54.1%, 39.3%, respectively. Multivariate analysis showed that age >65 years (DFS: HR=1.402, 95% CI: 1.022 to 1.922, P=0.036; OS: HR=1.461, 95% CI: 1.057 to 2.019, P=0.022), lymph node dissection number less than 25 (DFS: HR=1.348, 95% CI: 1.019 to 1.779, P=0.036; OS: HR=1.376, 95% CI: 1.035 to 1.825, P=0.028), pathological stage Ⅲ (DFS: HR=2.131, 95% CI: 1.444 to 3.144, P<0.01; OS: HR=2.079, 95% CI: 1.406 to 3.074, P<0.01), and no postoperative chemotherapy (DFS: HR=3.127, 95% CI: 2.377 to 4.113, P<0.01; OS: HR=3.768, 95% CI: 2.828 to 5.020, P<0.01) were independent prognostic factors for the decrease in DFS and OS rates. Conclusions:Laparoscopic radical gastrectomy for locally advanced gastric cancer with serosa-invasion could achieve satisfactory long-term oncological outcomes. More lymph node dissection and standardized postoperative adjuvant chemotherapy are expected to further improve the prognosis of patients with locally advanced gastric cancer with serous invasion after laparoscopic radical surgery.

Objective:To evaluate the long-term outcomes and prognostic factors of locally advanced gastric cancer with serosa-invasion.Methods:This study is a retrospective cohort study. The clinical and pathological data of 495 patients with locally advanced gastric cancer with serosa-invasion who underwent laparoscopic radical gastrectomy in Department of General Surgery, the First Hospital Affiliated to Army Medical University from October 2012 to October 2018 was analyzed retrospectively. There were 356 males and 139 females with an age ( M(IQR)) of 59 (16) years (range: 18 to 75 years). Observation indicators included postoperative results and long-term prognosis. The survival curve was drawn by the Kaplan-Meier method. Univariate and multivariate prognostic analysis was performed using the Cox proportional hazards model. Results:Among the 495 patients, a total of 57 patients (11.5%) were lost to follow-up, with a follow-up time of 89 (40) months (range: 23 to 134 months). The 5-year disease-free survival rate (DFS) and the 5-year overall survival rate (OS) were 56.0% and 58.2%, respectively. The 5-year DFS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 60.5%, 51.6%, 33.3%, respectively. The 5-year OS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 62.2%, 54.1%, 39.3%, respectively. Multivariate analysis showed that age >65 years (DFS: HR=1.402, 95% CI: 1.022 to 1.922, P=0.036; OS: HR=1.461, 95% CI: 1.057 to 2.019, P=0.022), lymph node dissection number less than 25 (DFS: HR=1.348, 95% CI: 1.019 to 1.779, P=0.036; OS: HR=1.376, 95% CI: 1.035 to 1.825, P=0.028), pathological stage Ⅲ (DFS: HR=2.131, 95% CI: 1.444 to 3.144, P<0.01; OS: HR=2.079, 95% CI: 1.406 to 3.074, P<0.01), and no postoperative chemotherapy (DFS: HR=3.127, 95% CI: 2.377 to 4.113, P<0.01; OS: HR=3.768, 95% CI: 2.828 to 5.020, P<0.01) were independent prognostic factors for the decrease in DFS and OS rates. Conclusions:Laparoscopic radical gastrectomy for locally advanced gastric cancer with serosa-invasion could achieve satisfactory long-term oncological outcomes. More lymph node dissection and standardized postoperative adjuvant chemotherapy are expected to further improve the prognosis of patients with locally advanced gastric cancer with serous invasion after laparoscopic radical surgery.

Objective:To investigate the effect and of piperine(PIP)on nerve injury in rats with cerebral infarction.Meth-ods:The rat model of cerebral infarction was prepared by modified thread embolism method.The rats were divided into Sham group,Model group,piperine group(PIP group,20 mg/kg piperine),piperine+PKA inhibitor group(PIP+H-89 group,20 mg/kg PIP+5 mg/kg H-89).The rats were scored for neurological impairment,the volume of cerebral infarction,neuronal damage and neuronal apoptosis were observed,and the levels of cAMP,IL-1β and IL-6 in hippocampus and the protein expressions of GFAP,NSE,AC6,PKA,p-CREB,CREB and BDNF were detected.Results:Compared with Sham group,Model group had large cerebral infarction,cerebral in-farction volume,the neurological deficit score,neuronal apoptosis rate,the levels of IL-6 and IL-1β in hippocampus,and number of GFAP positive cells,the positive expression rates of NSE protein increased,the number of Nissl bodies,and the expressions of cAMP,AC6,PKA,p-CREB and BDNF proteins in hippocampus decreased(P<0.05);compared with Model group,cerebral infarc-tion volume,the neurological deficit score,neuronal apoptosis rate,the levels of IL-6 and IL-1β in hippocampus,and number of GFAP positive cells,the positive expression rates of NSE protein in the PIP group decreased,the number of Nissl bodies,and the ex-pressions of cAMP,AC6,PKA,p-CREB and BDNF proteins in hippocampus increased(P<0.05);the effect of piperine in improving nerve injury in rats with cerebral infarction was able to be reversed by H-89.Conclusion:PIP can inhibit the apoptosis of hippocampal neurons,and improve the neural injury induced by cerebral infarction by activating AC/PKA/CREB signal pathway.

Heterogeneous nuclear ribonucleoprotein(hnRNP)and heterogeneous nuclear RNA(hnRNA)form complexes that regulate RNA splicing and transportation.hnRNPH1 is a member of the hnRNP family of proteins and plays an important role in physiological processes,including embryonic development of the nervous and reproductive systems.hnRNPH1 is highly expressed in various tumor tissues and tumor cells,and its overexpression correlates with poor prognosis in patients.hnRNPH1 enhances tumor cell proliferation and metastasis through the regulation of alternative splicing of genes,modulation of gene expression,formation of fusion genes with other genes,and involvement in epigenetic regulation.Recent studies have shown that hnRNPH1 could serve as a potential biomarker for certain tumors,and hnRNPH1-targeting drugs show preliminary efficacy in a mouse model of melanoma.This article reviews the role and research progress of hnRNPH1 in the initiation and progression of malignant tumors.

Objective:To investigate the application of cardiac magnetic resonance (CMR) quantitative techniques in evaluating myocardial involvement differences between new onset and longstanding systemic lupus erythematosus (SLE) patients.Methods:From August 2020 to April 2023, 14 new onset and 15 longstanding SLE patients treated at the First Affiliated Hospital of Anhui Medical University were prospectively included as the study group. Additionally, 18 age-, gender-, body surface area-, and body mass index-matched healthy volunteers were included as the control group. Clinical baseline data, electrocardiograms, and CMR results including left ventricular ejection fraction (LVEF), left ventricular end-systolic volume index (LVESVI), left ventricular end-diastolic volume index (LVEDVI), cardiac index (CI), left ventricular stroke volume index (LVSVI), left ventricular mass index (LVMI), myocardial strain, native T 1 values, and T 2 values were collected. One-way analysis of variance (ANOVA) or Kruskal-Wallis H test was used to compare the quantitative parameters among the three groups. Bonferroni correction was applied for pairwise group comparisons. Results:The native T 1 values [1 114.50 (1 089.33, 1 150.39) ms, 1 085.32 (1 051.31, 1 129.75) ms] and T 2 values [(55.9±3.4) ms, (53.3±1.5) ms] of new onset and longstanding SLE patients were higher than those of the healthy control group [native T 1 values 1052.62 (1024.75, 1077.59) ms, H=17.72, P<0.001; T 2 values (51.2±1.3) ms, F=18.70, P<0.001]. The T 2 values of the new onset SLE group was higher than that of the longstanding SLE group ( P<0.05). The LVEDVI[86.87 (80.80, 93.55) ml/m 2], LVSVI [54.63 (50.42, 59.03) ml/m 2], and LVMI [48.39 (41.65, 53.26) g/m 2] of the new onset SLE group were higher than those of the control group [LVEDVI: 71.11 (65.80, 81.28) ml/m 2, Z=3.02, P=0.003; LVSVI: 42.17 (40.36, 51.33) ml/m 2, Z=2.76, P=0.006; LVMI: 38.48 (35.22, 43.83) g/m 2, Z=3.10, P=0.002]. The LVEDVI and LVSVI of the new onset SLE group were also higher than those of the longstanding SLE group [LVEDVI: 73.30 (69.87, 84.71) ml/m 2, Z=1.97, P=0.048; LVSVI: 45.53 (42.28, 50.98) ml/m 2, Z=2.34, P=0.020]. Conclusion:Myocardial involvement is more severe in new onset SLE patients, whereas acute myocardial injury is alleviated in longstanding SLE patients. Therefore, early detection of cardiac involvement in SLE patients is crucial for improving prognosis.

Heterogeneous nuclear ribonucleoprotein(hnRNP)and heterogeneous nuclear RNA(hnRNA)form complexes that regulate RNA splicing and transportation.hnRNPH1 is a member of the hnRNP family of proteins and plays an important role in physiological processes,including embryonic development of the nervous and reproductive systems.hnRNPH1 is highly expressed in various tumor tissues and tumor cells,and its overexpression correlates with poor prognosis in patients.hnRNPH1 enhances tumor cell proliferation and metastasis through the regulation of alternative splicing of genes,modulation of gene expression,formation of fusion genes with other genes,and involvement in epigenetic regulation.Recent studies have shown that hnRNPH1 could serve as a potential biomarker for certain tumors,and hnRNPH1-targeting drugs show preliminary efficacy in a mouse model of melanoma.This article reviews the role and research progress of hnRNPH1 in the initiation and progression of malignant tumors.

Primary biliary cholangitis is a chronic autoimmune cholestatic disease with a progressive course. This disease is not rare in China, but standardized diagnosis and treatment for primary biliary cholangitis are insufficient. Based on the evidence and guidelines from China and other countries, Rheumatology Branch of Chinese Medical Association developed the recommendations of diagnosis and treatment for primary biliary cholangitis in China. The aim is to help clinicians recognize clinical characters, therapeutic selection and prognosis judgement of primary biliary cholangitis, which will contribute to make diagnosis in time, to select treatment properly and to manage follow-up scientifically.

Objective:To evaluate the effect of long-chain non-coding RNA MEG3(LncRNA MEG3) on the radiosensitivity of cervical cancer cells, and to explore its underlying mechanism.Methods:The expression of LncRNA MEG3 in cervical cancer cells was detected by qRT-PCR. In the overexpression control group (transfected with pcDNA 3.1), LncRNA MEG3 overexpression group (transfected with pcDNA 3.1-LncRNA MEG3), miR-NC inhibition group (transfected with anti-miR-NC), miR-181a-5p inhibition group (transfected with anti-miR-181a-5p), LncRNA MEG3+ miR-NC overexpression group (co-transfected with pcDNA3.1-LncRNA MEG3 and anti-miR-NC), LncRNA MEG3+ miR-181a-5p overexpression group (co-transfected with pcDNA 3.1-LncRNA MEG3 and anti-miR-181a-5p), all plasmids were transfected into SiHa cells by liposome method. The cell survival fraction was assessed by colony formation assay. The cell apoptosis rate was evaluated by flow cytometry. The cell fluorescence activity was assessed by dual luciferase reporter assay. The expression levels of PTEN, p-Akt and Akt proteins were detected by Western blot.Results:Compared with the radiosensitive group, the expression of LncRNA MEG3 was significantly down-regulated in radiation-resistant cervical cancer tissues ( P<0.05), and its expression level was positively correlated with the sensitivity of cervical cancer cells. Overexpression of LncRNA MEG3 or inhibition of miR-181a-5p could significantly enhance the irradiation sensitivity and promote the apoptosis of cervical cancer cell line SiHa (both P<0.05). The fluorescence activity of wild-type LncRNA MEG3 cells was inhibited by miR-181a-5p. Overexpression of miR-181a-5p reversed the irradiation sensitization and pro-apoptosis effect of LncRNA MEG3 and the regulation of the PTEN/Akt signaling pathway on cervical cancer cell. Conclusion:LncRNA MEG3 can enhance the sensitivity of cervical cancer cells to radiation exposure, probably by targeting the miR-181a-5p and regulating the PTEN/Akt signaling pathway, which will provide a new direction for improving clinical prognosis of cervical cancer patients.

Few tools of gene editing have been developed in Bacillus licheniformis at present. In order to enrich the tools, an FLP/FRT gene editing system that can repeatedly use a single selectable marker was constructed in Bacillus licheniformis, and the system was verified by knocking out an alpha amylase gene (amyL), an protease gene (aprE) and knocking in an exogenous Vitreoscilla hemoglobin gene (vgb). First, knock-out plasmids pNZTT-AFKF of amyL and pNZTT-EFKF of aprE were constructed using thermosensitive plasmid pNZT1 as a carrier. The two knock-out plasmids contained respective homology arms, resistance genes and FRT sites. Then the knock-out plasmids were transformed into Bacillus licheniformis and the target genes were replaced by respective deletion cassette via twice homologous exchange. Finally, an expression plasmid containing FLP recombinase reading frane was introduced and mediated the excision of resistance marker. In order to expand the practicability of the system, knock-in plasmid pNZTK-PFTF-vgb was constructed, with which knock-in of vgb at pflB site was carried out successfully. The results showed that amyL and aprE were successfully knocked out and the marker kanamycin cassette exactly excised. The activities of amylase and protease of deletion mutants were reduced by 95.3% and 80.4% respectively. vgb was successfully knocked in at pflB site and the marker tetracycline cassette excised. The expression of integrated vgb was verified via real-time PCR. It is the first time to construct an FLP/FRT system for gene editing in Bacillus licheniformis, which could provide an effective technical means for genetic modification.
Bacillus licheniformis ; Gene Editing ; Plasmids ; Sequence Deletion

Objective To investigate the predictive value of PCT for postoperative pancreatic fistula (POPF) in advance.Methods Clinical data of 62 consecutive patients who underwent pancreaticoduodenectomy(PD) and 19 consecutive patients who underwent distal pancreatectomy (DP) between Apr 2016 and Apr 2017 in the First Affiliated Hospital of Harbin Medical University and met the inclusion criteria were retrospectively collected and analyzed.Patients with PD and DP were divided into pancreatic fistula group (12 cases,3 cases),and non-pancreatic fistula group (50 cases,16 case).The PCT,CRP and WBC count levels of preoperative and postoperative day 1,3,5 (POD1,POD3,POD5) were compared between two groups.The data were subjected to independent sample t-test,Mann-Whitney rank sum test,x2 test or Fisher exact test.Receiver operating characteristic (ROC) curve was drawn and area under curve (AUC) was calculated to determine the cutoff value,sensitivity and specificity.Results For PD and DP patients,there were no significant difference on age,gender,BMI,diabetes,obstructive jaundice,preoperative laboratory test,operation time,intraoperative blood loss,tumor type between the two groups,which were comparable.For PD patients,postoperative hyperglycemia rate,postoperative ICU admission rate and total hospital stay of pancreatic fistula group were significantly higher than those of non-pancreatic fistula group (P =0.011,P =0.023,P ＜0.001).The PCT levels of POD1,POD3 and POD5 of pancreatic fistula group were significantly higher than those of non-pancreatic fistula group (P ＜ 0.001,P =0.010,P =0.002).PCT of POD1 had the highest sensitivity (100％) and specificity (80％) and PCT ＞0.76 μg/L was the risk factor for POPF.For DP patients,the PCT levels of POD1,POD3 and POD5 had the same predictive value for pancreatic fistula.Conclusion PCT has early predictive value for POPF of PD patients.