Objective To study the genetic variation of two mitochondrial DNA molecules (CO1 and Cytb gene) of Oncomelania hupensis isolated from different areas. Methods Snails were collected from Jingxi of Guangxi,Yueyang of Hunan and Eryuan of Yunnan. Genomic DNA was extracted from the snails,Co1 and Cytb gene fragments were amplified by PCR,then purified and sequenced. Sequences of each isolates were edited by using Clustal W(1.82) software,and the nucleotide composition,transition and transversion were accounted by using MEGA(3.1) software. The genetic distances were computed with Kimura method and phylogenetic trees were constructed with UPGMA and MP method respectively. Results CO1 and Cytb gene fragments were about 700 bp and 600 bp(including 2 primers) respectively. A total of 106 mutation spots (15.9%) were tested in CO1 homological nucleotides,and 165 mutation spots (28.5%) were tested in Cytb homological nucleotides. The distance matrix between Guangxi isolate and Hunan isolate was 0.051 and 0.031 for CO1 gene and Cytb gene respectively;while that between Guangxi and Yunnan isolates was 0.158 and 0.405 respectively. Phylogenetic trees constructed by UPGMA and MP took on the similar topo-structure:isolates of Guangxi and Hunan clustered into one group,while the Yunnan isolate exhibited as another group. Conclusion Oncomelania hupensis in Guangxi,Hunan and Yunnan are of relatively rich polymorphism in CO1 and Cytb genes in general.

Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are a type of newly discovered antibioticresistant bacteria. The rapid pandemic spread of NDM-1 bacteria worldwide (spreading to India, Pakistan, Europe, America, and Chinese Taiwan) in less than 2 months characterizes these microbes as a potentially major global health problem. The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations. The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics, allowing the bacteria to escape the action of antibiotics. Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues, the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified. Here, we report the three-dimensional structure of NDM-1 with two catalytic zinc ions in its active site. Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity. The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases (MBLs) and implicate its role in wide spectrum drug resistance. We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria. Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases.
Amino Acid Sequence ; Anti-Bacterial Agents ; metabolism ; Binding Sites ; Captopril ; chemistry ; pharmacology ; Catalytic Domain ; Crystallography, X-Ray ; Drug Resistance, Bacterial ; Enterobacteriaceae ; enzymology ; Molecular Sequence Data ; Sequence Alignment ; Sequence Homology, Amino Acid ; beta-Lactamases ; chemistry ; metabolism

Objective To observe the clinical effect of automated peritoneal dialysis(APD)in urgent-start peritoneal dialysis patients with stage 5 chronic kidney disease(CKD).Methods A total of 60 patients with end-stage renal disease who underwent urgent-start peritoneal dialysis in Shenyang Red Cross Hospital from June 2021 to December 2023 were selected as study objects.According to peritoneal dialysis,patients were divided into APD group and intermittent peritoneal dialysis(IPD)group,with 30 patients in each group.Renal function,electrolyte,parathyroid hormone,inflammatory factors,nutritional indexes,brain natriuretic peptide,blood pressure,urine volume,ultrafiltration volume and adverse reactions were compared between two groups.Results After treatment,serum creatinine,urea nitrogen,uric acid,potassium,phosphorus,parathyroid hormone,C-reactive protein,interleukin-6,brain natriuretic peptide,systolic blood pressure and diastolic blood pressure in two groups were significantly lower than before treatment,and urine volume was significantly higher than before treatment(P＜0.05).Serum creatinine,urea nitrogen,uric acid,potassium,phosphorus,parathyroid hormone,C-reactive protein,interleukin-6,brain natriuretic peptide,systolic blood pressure and diastolic blood pressure in APD group were significantly lower than those in IPD group,and ultrafiltration volume in APD group was significantly higher than that in IPD group(P＜0.05).After treatment,there was no significant difference in urine volume between two groups(P＜0.05).No serious complications and death were observed during treatment.Conclusion APD is safe and effective,and is a good choice for urgent-start peritoneal dialysis in stage 5 CKD patients.

Objective:To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate.Methods:Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups.Results:A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. ① There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE Ⅱ: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [μmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. ② Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). ③ Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. ④ Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. Conclusions:CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

Objective:To investigate the safety and short-term efficacy of laparoscopic pro-ximal gastrectomy (LPG) for proximal gastric cancer and adenocarcinoma of esophagogastric junction.Methods:The retrospective cohort study was conducted. The clinicopathological data of 385 patients with proximal gastric cancer and adenocarcinoma of esophagogastric junction who underwent LPG in the 15 medical centers, including the First Affiliated Hospital of Xiamen University et al, from January 2014 to March 2022 were collected. There were 304 males and 81 females, aged (63±9)years. Of the 385 patients, 335 cases undergoing LPG were divided into the laparoscopic group and 50 cases undergoing open proximal gastrectomy were divided into the open group. Observation indicators: (1) intraoperative and postoperative situations; (2) follow-up; (3) stratified analysis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Intraoperative and postoperative situations. The operation time, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, cases with postoperative pathological staging as stage 0?Ⅰ and stage Ⅱ?Ⅲ, duration of postoperative hospital stay, cases with postoperative early complications were (212±96)minutes, 270, 65, 177, 107, 10(range, 8?14)days, 40 in patients of the laparoscopic group, with 51 cases missing the data of postoperative pathological staging. The above indicators were (174±90)minutes, 39, 11, 22, 28, 10(range, 8?18)days, 10 in patients of the open group. There were significant differences in the opera-tion time and postoperative pathological staging between the two groups ( t=2.62, χ2=5.93, P<0.05), and there was no significant difference in the reconstruction of digestive tract, duration of post-operative hospital stay, postoperative early complications between the two groups ( χ2=0.19, Z=0.40, χ2=2.50, P>0.05). (2) Follow-up. Of the 385 patients,202 cases were followed up during the post-operative 12 months, including 187 cases in the laparoscopic group and 15 cases in the open group. Cases with reflux esophagitis, cases with esophageal anastomotic stenosis were 48, 11 in patients of the laparoscopic group, versus 5, 2 in patients of the open group, showing no significant difference in the above indicators between the two groups ( P>0.05). The body mass index (BMI), hemoglobin (Hb), albumin (Alb) at postoperative 6 months and 12 months were (21±3)kg/m 2, (130±15)g/L, (40±4)g/L and (21±3)kg/m 2, (132±14)g/L, (41±4)g/L in patients of the laparoscopic group, versus (21±3)kg/m 2, (121±19)g/L, (37±5)g/L and (21±3)kg/m 2, (125±21)g/L, (43±6)g/L in patients of the open group. There were significant differences in postoperative Hb between the two groups ( Fgroup=5.88, Ftime=5.49, Finteraction=19.95, P<0.05) and there were significant differences in time effect of postopera-tive BMI and Alb between the two groups ( Ftime=9.53, 49.88, P<0.05). (3) Stratified analysis. ① Incidence of postoperative of reflux esophagitis and esophageal anastomotic stenosis in patients with different reconstruction of digestive tract. Of the 202 patients, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis were 168 and 34, respectively. The incidence rates of postoperative of reflux esophagitis were 26.79%(45/168)and 23.53%(8/34)in cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, showing no significant difference between them ( χ2=0.16, P>0.05). Cases undergoing esophageal anastomotic stenosis were 13 in patients with reconstruction of diges-tive tract as esophagogastric anastomosis. ② The BMI, Hb, Alb in patients with different reconstruc-tion of digestive tract. The BMI, Hb, Alb were (24±3)kg/m 2, (135±20)g/L, (41±5)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis before the operation, versus (23±3)kg/m 2, (130±19)g/L, (40±4)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis before the operation, showing no significant difference between them ( t=1.44, 1.77, 1.33, P>0.05). The BMI, Hb, Alb at postoperative 6 months and 12 months were (21±3)kg/m 2, (128±16)g/L, (39±4)g/L and (21±3)kg/m 2, (131±16)g/L, (41±4)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis, versus (20±4)kg/m 2, (133±13)g/L, (43±3)g/L and (21±3)kg/m 2, (135±12)g/L, (44±3)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis. There were significant differences in the group effect and time effect of postoperative Alb between patients with different reconstruction of diges-tive tract ( Fgroup=15.82, Ftime=5.43, P<0.05), and there was also a significant difference in the time effect of postoperative BMI between them ( Ftime=4.22 , P<0.05). Conclusion:LPG can be used to the treatment of proximal gastric cancer and adenocarcinoma of esophagogastric junction, with a good safety and short-term efficacy.

In recent years, the incidence of adenocarcinoma of esophagogastric junction (AEG) keeps increasing. Siewert type II and type III AEG invades at 2?4 cm in the lower esophagus, and it has a higher rate of lower mediastinal lymph node metastasis. Lower mediastinal lymph node clearing through the abdomino?transhiatal (TH) approach is preferred, which can be accomplished by entering the lower mediastinum through the hiatus and mobilize the esophagus upward and the surrounding lymph and connective tissue for approximately 6.5 cm. Using the infracardiac bursa (IBC) as an anatomical landmark improves the safety and operability of the thorough dissection of the lower mediastinum. Total resection of the mesenterium at the esophagogastric junction can entirely dissect the lower mediastinal lymph nodes, which conforms to the safety principles in oncology.

In recent years, the incidence of adenocarcinoma of esophagogastric junction (AEG) keeps increasing. Siewert type II and type III AEG invades at 2?4 cm in the lower esophagus, and it has a higher rate of lower mediastinal lymph node metastasis. Lower mediastinal lymph node clearing through the abdomino?transhiatal (TH) approach is preferred, which can be accomplished by entering the lower mediastinum through the hiatus and mobilize the esophagus upward and the surrounding lymph and connective tissue for approximately 6.5 cm. Using the infracardiac bursa (IBC) as an anatomical landmark improves the safety and operability of the thorough dissection of the lower mediastinum. Total resection of the mesenterium at the esophagogastric junction can entirely dissect the lower mediastinal lymph nodes, which conforms to the safety principles in oncology.

Raspberry ketones have important therapeutic properties such as anti-influenza and prevention of diabetes. In order to obtain raspberry ketone from Chlamydomonas reinhardtii, two enzymes catalyzing the last two steps of raspberry ketone synthesis, i.e. 4-coumaryl-CoA ligase (4CL) and polyketide synthase (PKS1), were fused using a glycine-serine-glycine (GSG) tripeptide linker to construct an expression vector pChla-4CL-PKS1. The fusion gene 4CL-PKS1 driven by a PSAD promoter was transformed into a wild-type (CC125) and a cell wall-deficient C. reinhardtii (CC425) by electroporation. The results showed the recombinant C. reinhardtii strain CC125 and CC425 with 4CL-PKS1 produced raspberry ketone at a level of 6.7 μg/g (fresh weight) and 5.9 μg/g (fresh weight), respectively, both were higher than that of the native raspberry ketone producing plants (2-4 μg/g).
Acyl Coenzyme A ; Butanones ; Chlamydomonas reinhardtii/genetics* ; Ligases ; Polyketide Synthases

In recent years, the incidence of adenocarcinoma of esophagogastric junction (AEG) keeps increasing. Siewert type II and type III AEG invades at 2-4 cm in the lower esophagus, and it has a higher rate of lower mediastinal lymph node metastasis. Lower mediastinal lymph node clearing through the abdomino-transhiatal (TH) approach is preferred, which can be accomplished by entering the lower mediastinum through the hiatus and mobilize the esophagus upward and the surrounding lymph and connective tissue for approximately 6.5 cm. Using the infracardiac bursa (IBC) as an anatomical landmark improves the safety and operability of the thorough dissection of the lower mediastinum. Total resection of the mesenterium at the esophagogastric junction can entirely dissect the lower mediastinal lymph nodes, which conforms to the safety principles in oncology.