Objective To study the applicability and optimization of computer simulation methods during the allocation of health care providers for medical evacuation on board medical trains.Methods Using Anylogic as a simulation modeling tool,the process of mass evacuation of the injured by means of medical trains was simulated.The simulated process of rescue involved the generation,categorization,treatment and surgery of the injured individuals.The allocation of health care resources was assessed based on the different rates at which the injured arrived.Results In the carriage for mild to moderate patients,24 doctors and 36 nurses could meet the need of treatment.In the carriage for critically ill ones,4 doctors and 6 nurses could meet the need when the rate at which the injured arrived was 100-200 people/an hour.When the injured arrived at the rate of 300-476 people/an hour,4 doctors and 8 nurses were needed.Conclusion Computer simulation can be feasibly used to study the allocation of human resources for health care,which can facilitate decision-making about mass evacuation of injured personnel by means of medical trains.

Objective:The aim of this study was to evaluate the impact of neoadjuvant radiotherapy on anorectal function of patients with mid-low rectal cancer by means of high-resolution anorectal manometry.Methods:A retrospective observational study was conducted. Information on patients with mid-low rectal cancer was collected from the prospective registry database of Rectal Cancer at Peking Union Medical College Hospital (PUMCH) from June 2020 to April 2023. Anorectal functions were detected using three-dimensional high-resolution manometry system. Logistic regression analysis was performed to identify the factors associated with the changed anorectal manometry.Results:A total of 45 patients with mid-low rectal cancer were included in the study. Thirty-two (71.1%) patients were male, 13 (28.9%) patients were female. The mean age was 60±11 years, and the mean BMI was 23.4±3.7 kg/m 2. The mean distance between the lower edge of the tumor and the anal verge was 5.4±1.5 cm. The median size of the tumor was 3.4 (2.9-4.5) cm, and the median circumferential extent of the tumor was 66.0 (45.5-75.0) %. 41 (81.1%) patients were MRI T3-4 and 40 (88.9%) patients were MRI N positive. The resting pressure has a decreasing trend after neoadjuvant radiotherapy (55.3±32.0 mmHg vs. 48.0±28.5 mmHg, t=1.930, P=0.060). There was no significant change in maximum squeezing and the length of the high-pressure zone after neoadjuvant radiotherapy. All volumes describing rectal sensitivity (first sensation, desire to defecate, and maximum tolerance) were lower after neoadjuvant radiotherapy. And maximum tolerance was significantly lower (66.0 [49.0,88.0] ml vs. 52.0 [39.0,73.5] ml, Z=-2.481, P=0.013). Univariate analysis demonstrated that the downstage of N-stage was associated with the decrease in maximum tolerance (OR=6.533, 95%CI:1.254-34.051, P=0.026). Conclusion:Neoadjuvant radiotherapy damages anorectal function by decreasing the resting pressure and rectal sensory threshold of patients. The N-stage downstaging was associated with a decrease in maximum tolerance.

Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.

Objective:The aim of this study was to evaluate the impact of neoadjuvant radiotherapy on anorectal function of patients with mid-low rectal cancer by means of high-resolution anorectal manometry.Methods:A retrospective observational study was conducted. Information on patients with mid-low rectal cancer was collected from the prospective registry database of Rectal Cancer at Peking Union Medical College Hospital (PUMCH) from June 2020 to April 2023. Anorectal functions were detected using three-dimensional high-resolution manometry system. Logistic regression analysis was performed to identify the factors associated with the changed anorectal manometry.Results:A total of 45 patients with mid-low rectal cancer were included in the study. Thirty-two (71.1%) patients were male, 13 (28.9%) patients were female. The mean age was 60±11 years, and the mean BMI was 23.4±3.7 kg/m 2. The mean distance between the lower edge of the tumor and the anal verge was 5.4±1.5 cm. The median size of the tumor was 3.4 (2.9-4.5) cm, and the median circumferential extent of the tumor was 66.0 (45.5-75.0) %. 41 (81.1%) patients were MRI T3-4 and 40 (88.9%) patients were MRI N positive. The resting pressure has a decreasing trend after neoadjuvant radiotherapy (55.3±32.0 mmHg vs. 48.0±28.5 mmHg, t=1.930, P=0.060). There was no significant change in maximum squeezing and the length of the high-pressure zone after neoadjuvant radiotherapy. All volumes describing rectal sensitivity (first sensation, desire to defecate, and maximum tolerance) were lower after neoadjuvant radiotherapy. And maximum tolerance was significantly lower (66.0 [49.0,88.0] ml vs. 52.0 [39.0,73.5] ml, Z=-2.481, P=0.013). Univariate analysis demonstrated that the downstage of N-stage was associated with the decrease in maximum tolerance (OR=6.533, 95%CI:1.254-34.051, P=0.026). Conclusion:Neoadjuvant radiotherapy damages anorectal function by decreasing the resting pressure and rectal sensory threshold of patients. The N-stage downstaging was associated with a decrease in maximum tolerance.

Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.

Objective:To investigate the incidence and influencing factors of anastomotic leakage after laparoscopic anterior resection for rectal cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 804 patients with rectal cancer who were admitted to Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from January 2017 to December 2019 were collected. There were 521 male and 283 female, aged 63(range, 27-94)years. All 804 patients underwent laparoscopic anterior resection for rectal cancer. Observation indicators: (1) surgical situations; (2) incidence of postoperative anastomotic leakage; (3) follow-up; (4) influencing factors of postoperative anastomotic leakage; (5) subgroup analysis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribu-tion were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Univariate analysis was conducted using the chi-square test or independent sample t test. Factors with P≤0.2 in univariate analysis were included in multivariate Logistic regression analysis. Results:(1) Surgical situations. All 804 patients underwent laparoscopic radical resection of upper and middle rectal cancer successfully, with the operation time and volume of intraoperative blood loss as 135(range, 118-256)minutes and 30(range, 5-350)mL. All 804 patients completed end-to-end colon rectal anastomosis, including 287 patients with reinforced sutures at the anastomotic site, and 517 patients with routine anastomosis. (2) Incidence of postoperative anastomotic leakage. Of the 804 patients, 40 patients had postoperative anastomotic leakage, with the incidence rate as 4.98%(40/804). (3) Follow-up. All 804 patients were followed up for 32(range, 6-49)months. None of patient died during the perioperative period. (4) Influencing factors of postoperative anastomotic leakage. Results of multivariate analysis showed that unreinforced suture at the anastomotic site was an independent risk factor for postoperative anastomotic leakage ( odds ratio=2.78, 95% confidence interval as 1.21-6.37, P<0.05). (5) Subgroup analysis. Of the 804 patients, 202 patients received neoadjuvant therapy and 602 patients did not receive neoadjuvant therapy. Of the 602 patients who did not receive neo-adjuvant therapy, cases with postoperative anastomotic leakage was 6 in the 253 patients with reinforced sutures, versus 21 in the 349 patients with routine sutures, showing a significant difference between them ( χ2=4.56, P<0.05). Conclusion:Unreinforced anastomosis at the anasto-motic site is an independent risk factor for anastomotic leakage after laparoscopic anterior rectal resection, especially for rectal cancer patients without neoadjuvant radiochemotherapy.

Objective To analyze the heat-clearing and anti-inflammatory mechanism of Xiaoyan Tuire Granules by network pharmacology,and to determine the 8 main active components of Xiaoyan Tuire Granules by ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS/MS).Methods SwissTargetPrediction database was used to screen the target of components absorbed in the blood of Xiaoyan Tuire Granules.The main target of disease was obtained by CTD database,and the protein-protein interaction(PPI)was analyzed by String platform.GO and KEGG enrichment analysis were conducted using the DAVID database,followed by the construction of the components-targets-pathways network using Cytoscape software.Finally,the molecular docking verification of the key compound-target was conducted.The main active components in Xiaoyan Tuire Granules,including indirubin,isoliquiritigenin,liquiritigenin,glycyrrhizinic acid,liquiritin,esculetin,caffeic acid and chlorogenic acid,were determined by UPLC-MS/MS method.Analysis was performed on a WATERS ACQUITY UPLC? BEH C18 column(2.1 mm×100 mm,1.7 μm)with gradient elution of 0.1%formate in acetonitrile(A)-0.1%formate-5 mmol·L-1 ammonium formate(B),and the determination was carried out in multiple reaction monitoring(MRM)mode.Results Sixteen potential active components,such as indirubin,esculetin,and caffeic acid were identified by network pharmacology and molecular docking,and 10 core targets including transcription factor AP-1(JUN),adhesive connexin β1(CTNNB1)and cysteine aspartic protease-3(CASP3)were predicted.The pathway enrichment analysis revealed that heat-clearing and anti-inflammatory effects of Xiaoyan Tuire Granules were mainly related to signaling pathways such as interleukin-17(IL-17)and hypoxia-induced cause-1(HIF-1).Molecular docking experiments showed that its main active components docked well with core targets.The results of content determination exhibited that all components had good linear relationship within certain concentration range(r＞0.999),good precision,repeatability,and stability.The contents of 8 components in 16 batches of samples were 0.94-3.41,0.99-5.61,0.80-5.84,85.48-141.11,4.30-10.09,152.35-271.80,11.31-26.94,1.99-5.58 μg·g-1,respectively.The contents of indirubin,isoliquiritigenin,liquiritigenin,liquiritin,and chlorogenic acid in Xiaoyan Tuire Granules from two manufacturers were significantly different.Conclusion This study preliminarily revealed the mechanism of Xiaoyan Tuire Granules,which exerted heat-clearing and anti-inflammatory effects through multiple components,targets and pathways.A method for the determination of multiple components in Xiaoyan Tuire Granules was established.This study may provide a reference for its pharmacological research and quality control.

Gastric cancer with hemorrhage and cerebral infarction is a serious complica-tion with poor prognosis in clinic. Although the incidence rate is extremely low, the fatality and disability rates are very high. In addition, the opposition in treatment between the two complica-tions increases the difficulty of clinical diagnosis and treatment. The authors report the diagnosis and treatment of a gastric cancer patient with hemorrhage and new cerebral infarction, in order to to provide reference for related treatments.

Objective:To discuss the treatment methods for old pelvic fractures and urethral injuries in young girls.Methods:We retrospectively analyzed the clinical data of 10 girls, mean age of(8.5±4.3)years with old pelvic fractures and urethral injuries treated with different surgical methods in our hospital from April 2015 to April 2023. 7 cases were complicated with urethrovaginal fistula, 1 case was complicated with vesicovaginal fistula; 5 patients had distal urethral atresia or stenosis; 5 cases complicated with vaginal stenosis or partial atresia. One case underwent repair of urethrovaginal fistula via transpertoineal approach, two cases underwent urethral anastomosis (end to end anastomosis) via transpubic approach, one case underwent repair of urethrovaginal fistula and bladder neck urethral anastomosis via transpubic approach, four cases underwent urethroplasty repair of urethrovaginal fistula and bladder neck reconstruction surgery, one underwent urethroplasty and bladder neck reconstruction surgery via transpubic approach, one underwent augmented enterocystoplasty and continent urinary diversion by using the appendix. Observe the urination condition after operation (Urinary incontinence is defined as the use of more than 1 piece of urine pad per day, good urination is defined as the use of ≤ 1 piece of urine pad per day, and dysuria is defined as the complaint of laborious urination, and the maximum urine flow rate is less than 10 ml/s).Results:All surgeries were successfully completed without complications such as wound infection or tissue necrosis.The postoperative follow-up time was (52.0±26.2) months. 2 cases achieved good continence and no dysuria.Postoperative complications occurred in 7 cases, of which 2 cases had dysuria due to urethral stricture and improved after urethral dilatation; 5 cases of urethrovaginal fistula recurred, of which 3 cases had undergone rerepair surgery, and 2 of them achieved good urinary control without dysuria. One case with enterocystoplasty and contiunent urinary diversion recovered well after surgery.Conclusions:The management of old pelvic fractures and urethral injuries in girls is complicated, with a high rate of postoperative complications. It is necessary to choose appropriate treatment methods based on age, severity of the lesion, and urethral and vaginal conditions.

Promoter is an important genetic tool for fine-tuning of gene expression and has been widely used for metabolic engineering. Corynebacterium glutamicum is an important chassis for industrial biotechnology. However, promoter libraries that are applicable to C. glutamicum have been rarely reported, except for a few developed based on synthetic sequences containing random mutations. In this study, we constructed a promoter library based on the native promoter of odhA gene by mutating the -10 region and the bystanders. Using a red fluorescent protein (RFP) as the reporter, 57 promoter mutants were screened by fluorescence imaging technology in a high-throughput manner. These mutants spanned a strength range between 2.4-fold and 19.6-fold improvements of the wild-type promoter. The strongest mutant exhibited a 2.3-fold higher strength than the widely used strong inducible promoter P_trc. Sequencing of all 57 mutants revealed that 55 mutants share a 1-4 bases shift (4 bases shift for 68% mutants) of the conserved -10 motif "TANNNT" to the 3' end of the promoter, compared to the wild-type promoter. Conserved T or G bases at different positions were observed for strong, moderate, and weak promoter mutants. Finally, five promoter mutants with different strength were employed to fine-tune the expression of γ-glutamyl kinase (ProB) for L-proline biosynthesis. Increased promoter strength led to enhanced L-proline production and the highest L-proline titer of 6.4 g/L was obtained when a promoter mutant with a 9.8-fold higher strength compared to the wild-type promoter was used for ProB expression. The use of stronger promoter variants did not further improve L-proline production. In conclusion, a promoter library was constructed based on a native C. glutamicum promoter P_odhA. The new promoter library should be useful for systems metabolic engineering of C. glutamicum. The strategy of mutating native promoter may also guide the construction of promoter libraries for other microorganisms.
Corynebacterium glutamicum/metabolism* ; Gene Library ; Metabolic Engineering ; Promoter Regions, Genetic/genetics*