Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

OBJECTIVES: To explore the effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on 16S rDNA technique. METHODS: Ten rats were randomized from 58 SPF-grade male SD rats to be the blank group. The remained 48 rats were prepared to be IBS-D models by the modified method of acetic acid enema combined with binding tail-clip stress. Forty successfully-modeled rats were randomly divided into a model group, an acupuncture group, a moxibustion group and a western medication group, with 10 rats in each one. In the acupuncture group, the needle was inserted at bilateral "Zusanli" (ST 36) and remained for 15 min in each rat. In the moxibustion group, the suspending moxibustion was delivered at bilateral "Zusanli" (ST 36) for 15 min. The rats in the western medication group were given pinaverium bromide suspension (10 mL/kg) by intragastric administration. The above interventions were performed once daily for consecutive 14 days. The body mass and the score of fecal trait were compared before and after modeling, as well as after intervention in each group. Fecal water content, diarrhea index and colon transit time (CTT) were measured after modeling and intervention in the rats of each group separately. After intervention, the colonic morphology of rats in each group was observed, and using 16S rDNA technique, the intestinal flora was detected. RESULTS: After modeling, compared with the blank group, the body mass and CTT were reduced (P<0.01); fecal trait scores, fecal water contents and diarrhea index increased (P<0.01) in the other 4 groups. After intervention, the body mass and CTT of the rats decreased (P<0.01), and fecal trait score, fecal water content and diarrhea index increased (P<0.01) in the model group compared with those in the blank group. In the acupuncture group, the moxibustion group and the western medication group, when compared with the model group, the body mass and CTT were elevated (P<0.01), while fecal trait scores, fecal water contents and diarrhea index declined (P<0.01). Compared with the western medication group, fecal water content decreased in the acupuncture group and the moxibustion group (P<0.05), while CTT increased in the acupuncture group (P<0.01), the body mass increased and fecal trait score was dropped in the moxibustion group (P<0.05). The colonic mucosa structure was clear and complete, and there was no obvious inflammatory cell infiltration in the blank group. The mild interstitial edema of intestinal mucosa was presented with the infiltration of few inflammatory cells in the model group. There was the infiltration of few inflammatory cells in the mucosa of the acupuncture group, the moxibustion group and the western medication group. Compared with the blank group, the indexes of Richness, Chao1, ACE and Shannon decreased in the model group (P<0.05). Indexes of Richness, Chao1 and ACE increased in the acupuncture group and the moxibustion group (P<0.05), and the Richness index in the western medication group increased (P<0.05) when compared with those in the model group. The relative abundance of Bacteroidetes, Proteobacteria and Prevotella increased (P<0.05), and that of Firmicutes and Muribaculaceae decreased (P<0.05) in the model group compared with those in the blank group. When compared with the model group, the relative abundance of Bacteroidetes, Proteobacteria and Prevotella was reduced (P<0.05), while that of Firmicutes and Muribaculaceae increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group; and that of Actinobacteria and Bifidobacterium increased in the acupuncture group and the moxibustion group (P<0.05). Compared with the blank group, the relative abundance of lipopolysaccharide (LPS) biosynthesis was elevated (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis decreased (P<0.05) in the model group. The relative abundance of LPS biosynthesis was dropped (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group compared with those of the model group. CONCLUSIONS Either acupuncture or moxibustion can relieve the symptoms of IBS-D and protect intestinal mucosa, which may be associated with regulating the structure of intestinal flora and promoting nutrient metabolism and biosynthesis.
Rats ; Male ; Animals ; Irritable Bowel Syndrome/therapy* ; Moxibustion/methods* ; Rats, Sprague-Dawley ; Gastrointestinal Microbiome ; Lipopolysaccharides ; Thioctic Acid ; Ubiquinone ; Zeatin ; Acupuncture Therapy ; Diarrhea/therapy* ; Terpenes ; Water ; Folic Acid ; Acupuncture Points

Objective:To explore the effect of mini-clinical evaluation exercise (MiniCEX) and direct observation of procedural skills (DOPS) formative evaluation in standardized residency training of respiratory and critical care medicine.Methods:The residents who participated in standardized residency training of Zhongshan Hospital, Fudan Unviersity in 2019 were collected in study group, and the residents received the training in previous were collected in control group. The graduation examination scores, the effect of progressive rotations and the satisfaction of residents and examiners were compared between the two groups.Results:The scores of medical history writing, operation and clinical abilities were higher in the study group who were received MiniCEX-DOPS formative evaluation than those in the control group ( P<0.05). The scores of MiniCEX-DOPS evaluation in the third rotation were better than those in the first rotation ( P<0.05). The residents and examiners were generally satisfied with MiniCEX-DOPS evaluation. Conclusion:MiniCEX-DOPS evaluation is effective in residents training of respiratory and critical care medicine, and it is worth popularizing.

Objective To investigate the prevalence and influencing factors of intestinal protozoan infections among rural children in Henan Province. Methods A total of 104 survey sites were sampled from 35 counties (cities) in Henan Province using the stratified cluster sampling method to investigate the prevalence of intestinal protozoan infections among rural children from 2014 to 2015. The trophozoites and cysts of intestinal protozoa were identified using the iodine staining method and the physiological saline direct smear method (one detection for one stool sample). The prevalence of intestinal protozoan infections was compared among rural children with different characteristics, and the factors affecting intestinal protozoan infections among rural children were identified. Results The overall prevalence of intestinal protozoan infections was 0.60% (40/6 771) among rural children in Henan Province from 2014 to 2015. There were 7 species of intestinal protozoa identified, and there was no species-specific prevalence (χ² = 37.732, P = 0.000). No significant differences were found in prevalence of intestinal protozoan infections among rural children in terms of gender (χ² = 1.793, P = 0.181), age (χ² = 1.443, P = 0.486), occupation (χ² = 0.219, P = 0.896) or ecological region (χ² = 1.700, P = 0.637). In addition, terrain (χ² = 2.311, P = 0.510), economic level (χ² = 4.322, P = 0.229), source of drinking water (χ² = 0.731, P = 0.393), eating raw vegetables (χ² = 1.134, P = 0.287) and deworming (χ² = 1.089, P = 0.297) had no remarkable effects on the prevalence of intestinal protozoan infections among rural children in Henan Province; however, the prevalence of intestinal protozoan infections varied significantly among rural children living in regions with different coverage of non-harmless toilets (χ² = 10.050, P = 0.018). Conclusion The prevalence of intestinal protozoan infections is low among rural children in Henan Province.

ObjectiveQuorum-sensing (QS) and small regulatory RNA (sRNA) play key regulatory roles in many signaling cascades of Pseudomonas aeruginosa. To investigate whether sRNA is involved in P. aeruginosa QS system, screening QS system-related sRNA, and to construct sRNA overexpression and deletion strains of Pseudomonas aeruginosa for further study of sRNA function.MethodsSRNA associated with the QS system was screened by qPCR and RNA-sequencing (RNA-seq). The target gene were amplified by PCR and inserted into the overexpression vector pROp200 or the homologous recombination vector pGSM-MR, respectively. The connection reaction solution of pROp200-sRNA and pGSM-ΔsRNA was transformed into Escherichia coli DH5a and SM10lp, respectively. The recombinant vectors were identified by PCR. The pROp200-sRNA was transformed into PAO1 by heat shock method, and the pGSM-ΔsRNA was transferred from SM10lp to PAO1 by conjugation. SRNA overexpression and deletion strains were identified by PCR, DNA sequencing and qPCR, the determination of the growth curves and the pyocyanin levels of strains.ResultsFive QS -associated sRNA P26, P5316.1, P30, P34 and AmiL were successfully screened by RNA-seq and qPCR. PCR, DNA sequencing and qPCR showed that sRNA of AmiL, P30 and P34 overexpression and knockout were successful. Compared with wild-type strain, sRNA overexpression and knockout had no significant effect on bacterial growth curve. It were notably that overexpression of AmiL and P30 inhibited and increase the production of pyocyanin, respectively (P<0.01), while deficiency of AmiL and P30 in the genome resulted in significantly increase and decrease of pyocyanin, respectively (P<0.01). Overexpression and deletion of P34 had no significant effect on pyocyanin synthesis (P>0.05).ConclusionThe sRNA overexpression and deletion strains have been successfully constructed and can be used to study the regulatory relationship between sRNA and QS systems, and to further functional study.

Objective:To evaluate the feasibility, safety and efficacy of robotic-assisted lateral lymph node dissection for mid-low advanced rectal cancer.Methods:A retrospective cohort study was performed. Inclusion criteria: (1) age between 18 and 80 years old; (2) rectal adenocarcinoma diagnosed by pathology; (3) without distant metastasis by preoperative CT or MRI; (4) patients underwent robotic-assisted total mesorectal resection (TME). Exclusion criteria: (1) conversion to open surgery; (2) multiple primary tumors; (3) patients underwent combined multiple organ resection. According to the above criteria, 137 patients undergoing robotic-assisted mid-low rectal cancer resection in the First Affiliated Hospital of Xi′an Jiaotong University from December 2016 to April 2019 were enrolled. Ninety-seven cases underwent robotic-assisted total mesorectal excision (TME group) and 40 underwent robotic-assisted total mesorectal resection with lateral lymph node dissection (LLND) (TME+LLND group, pelvic LLND was performed with neurovascular guidance to retain pelvic autonomic nerves in the order of the left side the first and then the right side). The propensity score matching of 1:1 was performed with R software, based on age, sex, BMI, ASA classification, distance from tumor to the anal verge, preoperative chemoradiotherapy history, preoperative abdominal surgery history, the size of tumors and TNM stage. The operative indicators, postoperative recovery, pathology and postoperative complications within 30 days were compared between the two groups.Results:A total of 72 cases were successfully matched (36 in each group), and there were no statistically significant differences in baseline data between the two groups (all P>0.05). The operation time of TME+LLND group was significantly longer than that of TME group [275.0 (180-405) minutes vs. 220.0 (140-320) minutes, Z=-3.680, P<0.001], while there were no statistically significant differences in blood loss during operation, time to postoperative first flatus, postoperative hospital stay, total hospital cost, tumor differentiation, and distal resection length of margin (all P>0.05). Circumferential resection margin was all negative in both groups. The number of harvested lymph modes in the TME+LLND groups was higher than that in the TME group [26 (18-37) vs. 14 (9-36), Z=-6.407, P<0.001]. In addition, there were no statistically significant differences in postoperative morbidity and Clavien-Dindo classification of complication within 30 days between the two groups (both P>0.05). Conclusions:Although robotic lateral lymph node dissection requires longer operation time, it is a feasible, safe and effective procedure.

Objective:To evaluate the feasibility, safety and efficacy of robotic-assisted lateral lymph node dissection for mid-low advanced rectal cancer.Methods:A retrospective cohort study was performed. Inclusion criteria: (1) age between 18 and 80 years old; (2) rectal adenocarcinoma diagnosed by pathology; (3) without distant metastasis by preoperative CT or MRI; (4) patients underwent robotic-assisted total mesorectal resection (TME). Exclusion criteria: (1) conversion to open surgery; (2) multiple primary tumors; (3) patients underwent combined multiple organ resection. According to the above criteria, 137 patients undergoing robotic-assisted mid-low rectal cancer resection in the First Affiliated Hospital of Xi′an Jiaotong University from December 2016 to April 2019 were enrolled. Ninety-seven cases underwent robotic-assisted total mesorectal excision (TME group) and 40 underwent robotic-assisted total mesorectal resection with lateral lymph node dissection (LLND) (TME+LLND group, pelvic LLND was performed with neurovascular guidance to retain pelvic autonomic nerves in the order of the left side the first and then the right side). The propensity score matching of 1:1 was performed with R software, based on age, sex, BMI, ASA classification, distance from tumor to the anal verge, preoperative chemoradiotherapy history, preoperative abdominal surgery history, the size of tumors and TNM stage. The operative indicators, postoperative recovery, pathology and postoperative complications within 30 days were compared between the two groups.Results:A total of 72 cases were successfully matched (36 in each group), and there were no statistically significant differences in baseline data between the two groups (all P>0.05). The operation time of TME+LLND group was significantly longer than that of TME group [275.0 (180-405) minutes vs. 220.0 (140-320) minutes, Z=-3.680, P<0.001], while there were no statistically significant differences in blood loss during operation, time to postoperative first flatus, postoperative hospital stay, total hospital cost, tumor differentiation, and distal resection length of margin (all P>0.05). Circumferential resection margin was all negative in both groups. The number of harvested lymph modes in the TME+LLND groups was higher than that in the TME group [26 (18-37) vs. 14 (9-36), Z=-6.407, P<0.001]. In addition, there were no statistically significant differences in postoperative morbidity and Clavien-Dindo classification of complication within 30 days between the two groups (both P>0.05). Conclusions:Although robotic lateral lymph node dissection requires longer operation time, it is a feasible, safe and effective procedure.

Objective: To evaluate combined robotic and endoscopic surgery in the third space for gastric submucosal tumors(SMTs). Methods: Combined surgery in 4 patients were compared with 19 patients who underwent laparoscopic wedge resection between Aug 2017 and Feb 2018. Results: R₀ resection was achieved in all combined surgery patients. The operation time was longer (112±29 )min vs. (93±11 ) min (t=2.338, P<0.05), but less blood loss, (11±6)ml vs.(59±6)ml (t=15.102, P<0.01). In combined surgery group, there was a larger tumor over resected tissue percentage, 65.4%±28.2% vs.22.8%±19.6% ( t=3.680, P<0.05). Combined surgery group patients were with earlier first breaking wind (3±1.4) d vs.(4.1±0.9) d (t=2.026, P>0.05), and shorter hospital stay (6.5±1.3) d vs.( 8.5±0.6) d (t=4.902, P<0.01), but a little higher hospitalization costs(57 651±10 097)rmb vs.(42 620±5 086)rmb (t=4.508, P<0.01). There were no major postoperative complications occurred in neither groups, nor tumor recurrences after 3-month follow-up. Conclusion Combined robotic and endoscopic surgery in the third space for submucosal gastric tumors is a novel operation with short operation time, less blood loss and good result.

Objective To evaluate the effect of Oncomelania hupensis snail control of cutting the beach group in the south of Shaobo Lake. Methods The general situation of the project of cutting the beach was surveyed, and the snail distribution was surveyed and the results were compared before and after cutting the beach in the beach group. Results The area of cutting beach was 928.33 hm², the cubic meter of earthwork was 1 717.00 m³, the area of dumping ground was 425.76 hm², the beach surface elevation was 3.2 m after cutting the beach, and the beach surface was fallen to 1.0 m under the ordinary water level. The area with snails was 44.69 hm² before cutting the beach in 2011 but the area with snails was 1.78 hm² after cutting the beach in 2018. The area with remaining snails was declined by 96.02% in 2018 as compared with that in 2011, and surviving snails were distributed on the uncut beach face. Conclusion In Shaobo Lake, the O. hupensis snail breeding environment is eliminated by raising or lowering the beach, so it is an effective measure of snail control in lake regions.

Objective To understand the epidemic status and influencing factors of intestinal parasitic diseases among rural children in Henan Province. Methods According to the Scheme for The National Survey on Current Status of Major Human Parasitic Diseases in China, the survey counties were selected based on the ecological zones and economic levels in Henan Province between 2014 and 2015. Then, the included counties were stratified according to the topography and economic levels. A township was randomly sampled from each stratum, and a village was randomly sampled from each township as the study site. Finally, a total of 104 study sites from 35 counties were enrolled for the survey of intestinal parasitic diseases in children. At least 250 fresh stool samples were collected from each study site for detection of intestinal helminth eggs with the Kato-Katz technique, for the identification of Necator americanus and Ancylostoma duodenale with the fecal culture method, and for the detection of intestinal protozoa trophozoite and cyst with the physiological saline smear and iodine staining techniques. In addition, the Enterobius vermicularis and tapeworm eggs were detected in children aged 3 to 6 years using the adhesive cellophane-tape perianal swab method. Results The overall prevalence of intestinal parasitic infections was 3.21% (214/6 671) among rural children in Henan Province, and the prevalence of intestinal helminthes (2.62%, 175/6 671) was higher than that of intestinal protozoa (0.60%, 40/6 671). A total of 12 species of intestinal parasites were found, including 4 nematodes species, one trematode species, and 7 protozoa species, and the highest infection was seen in E. vermicularis (2.47%, 161/6 671). Among the four ecological zones in Henan Province, the greatest prevalence of intestinal parasitic infections was detected among children in the Qinba Mountain Ecological Zone (5.85%, 90/1 538). There was no gender-specific difference in the prevalence of intestinal parasitic infections in children (P > 0.05); however, there were age- (χ² = 32.762, P < 0.05) and education level-specific differences in the prevalence of intestinal parasitic infections in children (χ² = 67.507, P < 0.05), with the greatest prevalence of E. vermicularis infection seen in all species of intestinal parasites in children at all age groups. Multivariate non-conditional logistic regression analysis showed that high education level, high coverage of harmless toilets, drinking tap water and deworming were protective factors for intestinal parasitic infections in children in Henan Province. The overall prevalence of intestinal parasitic infections appeared a tendency towards a gradual decline among children in Henan Province as compared to the previous two surveys. Conclusions The overall prevalence of intestinal parasitic infections shows a tendency towards a remarkable decline among children in Henan Province. E. vermicularis infection should be given a priority for future parasitic disease control activities among rural children in Henan Province.