Objective To develop a nomogram for predicting the risks of early anastomotic recurrence(EAR)after primary bowel resection in patients with Crohn's disease(CD).Methods The patients with CD under-going preoperative magnetic resonance enterography(MRE)and primary bowel resection were enrolled in this retrospective study and divided into an EAR group(18 patients)and EAR-free group(12 patients).The EAR group included the patients having an endoscopic Rutgeerts score of≥I2 month or the need for anastomotic resection within 12 months after surgery.All the 38 indexes including preoperative demographic characteristics,laboratory examina-tions,multi-parameter MRE features of the resected intestine and its adjacent mesentery,histological findings,and postoperative pharmacotherapy were analyzed.Least absolute shrinkage and selection operator(LASSO)regression and multivariate binary logistic regression analysis were performed to identify independent risk factors to be incorpo-rated into the nomogram for predicting the risks of early anastomotic recurrence and the prediction performance was evaluated.Results Mesenteric creeping fat index on MRE and comb sign were independent risks of EAR,with a concordance index of 0.882(95%CI:0.764～1).The calibration plot revealed a strong relationship between actual observation and predicted probability of EAR.Conclusions The preoperative MRE-based nomogram may be a potential tool for predicting EAR following surgery in patients with CD,which is beneficial to individual management in those patients.It provides reference for the formulation of early postoperative individualized drug adjuvant therapy in patients at high risk of EAR.

Objective:To study the risk factors of surgical therapy in neonates with necrotizing enterocolitis (NEC).Methods:From January 2016 to July 2020, neonates with a confirmed diagnosis of NEC (Bell's Stage Ⅱ and above) admitted to our hospital were retrospectively enrolled. They were assigned into surgical group and conservative group according to whether surgeries were performed. The conditions during perinatal period, clinical characteristics and laboratory examinations at the onset of NEC were compared between the two groups. Multivariate Logistic regression analysis was used to determine the risk factors of surgical therapy.Results:A total of 177 neonates with NEC were identified, including 62 cases (35.0%) in the surgical group and 115 cases (65.0%) in the conservative group. Multivariate Logistic regression analysis showed that male gender ( OR=3.178,95% CI 1.457~6.929, P=0.004), comorbidity with shock ( OR=3.434, 95% CI 1.112~10.607, P=0.032), mechanical ventilation>7 d before NEC onset ( OR=3.663, 95% CI 1.098~12.223, P=0.035) and lymphocytes <2.0×10 9/L ( OR=4.121, 95% CI 1.801~9.430, P=0.001) at the onset of NEC were independent risk factors for surgical therapy. Conclusions:Male gender, comorbidity with shock, mechanical ventilation >7 d before NEC and lymphocytopenia at the onset are independent risk factors for surgical therapy in neonates with NEC (Stage Ⅱ and above).

It is discovered that activated caspase-3 tends to induce apoptosis in gasdermin E (GSDME)-deficient cells, but pyroptosis in GSDME-sufficient cells. The high GSDME expression and apoptosis resistance of pancreatic ductal adenocarcinoma (PDAC) cells shed light on another attractive strategy for PDAC treatment by promoting pyroptosis. Here we report a hGLuc-hGSDME-PCA system for high-throughput screening of potential GSDME activators against PDAC. This screening system neatly quantifies the oligomerization of GSDME-N to characterize whether pyroptosis occurs under the stimulation of chemotherapy drugs. Based on this system, ponatinib and perifosine are screened out from the FDA-approved anti-cancer drug library containing 106 compounds. Concretely, they exhibit the most potent luminescent activity and cause drastic pyroptosis in PDAC cells. Further, we demonstrate that perifosine suppresses pancreatic cancer by promoting pyroptosis via caspase-3/GSDME pathway both in vitro and in vivo. Collectively, this study reveals the great significance of hGLuc-hGSDME-PCA in identifying compounds triggering GSDME-dependent pyroptosis and developing promising therapeutic agents for PDAC.

OBJECTIVE To explore and establis h a general pharmacist system suitable for China ’s national conditions ，and to improve the rational use of drugs in primary medical institutions . METHODS Under the leadership of Tianhe District Health Bureau of Guangzhou ，relying on the regional pharmaceutical specialty alliance ，general pharmacist system of medical consortium was established ，and the general pharmacist was responsible for the overall planning of pharmaceutical care in the medical consortium. The joint management office of pharmaceutical care was established ，and the training of the pharmacists in the medical consortium was organized. A regional audit center was established to realize the prescription review of 13 community health service centers in the medical consortium. “Internet plus ”home pharmaceutical care was carried out ，and science popularization education was provided for communities ，schools，enterprises and institutions. RESULTS After systematic training and assessment ，three pharmacist teams had been successfully established in the medical consortium to provide prescription review ，science popularization and education and family pharmacist services for community residents ；the regional audit center successfully intercepted 17.17％ of unreasonable prescriptions ，reducing the amount of unreasonable drug use by a total of 6.56 million yuan. After the intervention of prescription review system ，the qualified rate of outpatient prescriptions in community health service centers was ≥95％，and the qualified rate increased by an average of 6％. The department of pharmaceutical science popularization and education held 35 science popularization and free clinic activities ，of which 71.20％ of the residents believed that the activities had improved their understanding of drugs. In addition ，111 cases patients serviced by home pharmaceutical care were carried out successfully by pharmacist team ，and the patients ’acceptance of pharmacist intervention was 91.89％ . CONCLUSIONS Under the new medical reform ，it is feasible to implement a regional general pharmacist system within the medical consortium ， which improves the pharmaceutical administration and pharmaceuticalcare capabilities of m edical institutions in the medical consortium，as well as the level of rational drug use ，and reduces the me dical burden.

Objective     To investigate the vaccination rate of Coronavirus Disease 2019 (COVID-19) vaccine in patients undergoing cardiac mechanical valve replacement and to evaluate its effect on international normalized ratio (INR) value. Methods    We investigated 132 patients who had received cardiac mechanical valve replacement and followed up in the Department of Cardiovascular Surgery, West China Hospital of Sichuan University from May to October 2021. There were 51 males and 81 females aged 26-72 (53.01±9.51) years. Results    The vaccination coverage rate was 53.8%. Among the 61 unvaccinated patients, concerns about heart side-effects were the main reason. The average INR of the first review after vaccination was higher than that of the last review before vaccination, with a difference of 0.40±0.72 (P<0.001). Conclusion    The vaccination rate of patients after cardiac mechanical valve replacement is low. At the same time, COVID-19 vaccine may increase INR value, and it is suggested that patients should increase the frequency of review and adjust warfarin dosage after vaccination.

OBJECTIVE To exc avate the adverse drug event （ADE）signals of semaglutide and provide reference for its clinical rational use. METHODS The proportional unbalance method was used to mine the signals of all semaglutide ADE reports from FDA Adverse Event Reporting System （FAERS）up to September 2021. The basic situations of the reported cases were analyzed. The corresponding system organ classification （SOC）was mapped and compared with the adverse drug reactions recorded in the drug instructions. Preferred terms （PT）of patients with different indications were analyzed. RESULTS A total of 6 661 semaglutide ADE reports were extracted and 194 valid signals were mined. Among 6 661 cases of ADE ，the proportion of men （43.40％）was lower than women （52.65％）；the age was mainly distributed in ＞40-65 years old （29.00％）and ＞65 years old （22.61％）；the reporting country was mainly the United States （83.88％）；the report year was mainly concentrated in 2021 （40.88％），with an increasing trend year by year ；the main outcome was hospitalization or prolonged hospitalization in serious ADE reports （17.78％）. Semaglutide ADE signal was mapped to the main SOC ，mainly including gastrointestinal diseases ，various injuries，poisoning and operation complications ，metabolic and nutritional diseases ，various examinations. The screening criteria were based on the report odds ratio ＞10 or ADE reported cases ＞50，and 48 new potential adverse drug reactions were added to the drug description. Among the indications with the top two reported cases （type 2 diabetes and obesity ，overweight，weight control），the frequency of gastrointestinal system related ADE reports represented by nausea ，vomiting and diarrhea was higher ， which was similar to the drug instructions. CONCLUSIONS This study supplemented 48 new potential adverse drug reactions based on the drug instructions of semaglutide. At present ，it can be considered that semaglutide is safe.

【Objective】 To study the annual financial expenditure in blood stations with different scales, and to establish the regression equation between blood collection units and total expenditure. 【Methods】 The annual total expenditure, the per capita cost of serving population, as well as the collection units of whole blood and apheresis platelet of 24 blood stations were collected. The financial expenditure required for collecting 10 000U blood was calculated.The statistical analysis was carried out with SPSS statistical software. 【Results】 From 2017 to 2020, the total annual financial expenditure of 24 blood stations showed an upward trend. The total expenditure among blood stations was different. The per capita cost of servicing population in the areas where the 24 blood stations were located had been increasing year by year. The 24 blood stations were divided into two grades according to the blood collection volume as 50 000 U, and the relationship equation between the blood collection volume and the annual total expenditure had been established. After testing, each equation was effective(P<0.05); There was no difference in the financial expenditure required for collecting 10 000U blood among blood stations with different scales. 【Conclusion】 From 2017 to 2020, the blood stations with an annual collection volume more than 50 000 U demonstrated a higher financial expenditure and the per capita cost of serving population than those <50 000 U. The blood collection volume of blood stations is significantly correlated with the annual total expenditure and the per capita cost of serving population.

Objective:To study the risk factors of necrotizing enterocolitis (NEC) after surgery for intestinal atresia.Method:From August 2013 to June 2020, children with intestinal atresia receiving surgery in our hospital were retrospectively reviewed. The patients were assigned into NEC group and non-NEC group according to the occurrence of postoperative NEC. Demographic data and clinical characteristics were summarized and the risk factors for postoperative NEC were analyzed using Logistic regression analysis method.Result:A total of 96 infants were enrolled and NEC occurred in 13 patients (13.5%) after surgery for intestinal atresia. Compared with the non-NEC group, the NEC group were diagnosed of intestinal atresia [4.0(1.5,6.0)d vs. 1.4(0,2.0)d, P<0.001] and received surgery [4.8(2.0,7.0)d vs. 3.1(1.0,4.0)d, P=0.034] at later ages. The incidences of complex intestinal atresia [76.9%(10/13) vs. 44.6%(37/83), P=0.030] and blood transfusion [46.2%(6/13) vs. 13.3%(11/83), P=0.007] in the NEC group were higher than the non-NEC group. Logistic regression analysis showed that the age of initial diagnosis of intestinal atresia ( OR=3.346, 95% CI 1.493~7.500, P=0.003), complex intestinal atresia ( OR=9.052, 95% CI 1.119~73.209, P=0.039) and blood transfusion ( OR=6.835, 95% CI 1.399~33.380, P=0.018) were independent risk factors for postoperative NEC. Conclusion:Patients with delayed diagnosis of intestinal atresia, complex intestinal atresia and blood transfusion within 48 hours after surgery should be monitored for the occurrence of postoperative NEC.

The fcl gene encodes GDP-fucose synthase, which catalyzes two-step differential isomerase and reductase reactions in the synthesis of GDP-L-fucose from GDP-D-mannose. It also participates in the biosynthesis of amino sugar and ribose sugar, and is one of the key enzymes to regulate the metabolism of sugar and nucleotides in organisms. The presence of fcl gene in Saccharopolyspora pogona was found through sequencing result of genome. The mutant S. pogona-fcl and S. pogona-Δfcl were constructed by gene engineering technology. The results showed that the gene had an effects on growth and development, protein expression and transcriptional level, insecticidal activity, and biosynthesis of butenyl-spinosyn of Saccharopolyspora pogona. The results of HPLC analysis showed that the yield of butenyl-spinosyn in S. pogona-Δfcl was 130% compared with that in S. pogona, which reduced by 25% in S. pogona-fcl. The results of determination of insecticidal activity showed that S. pogona-Δfcl had a stronger insecticidal activity against Helicoverpa armigera than that of S. pogona, while the S. pogona-fcl had a lower insecticidal activity against Helicoverpa armigera compared with S. pogona. Scanning electron microscopy (SEM) was used to observe the morphology of the mycelia. It was found that the surface of the S. pogona-Δfcl was wrinkled, and the mycelium showed a short rod shape. There was no significant difference in mycelial morphology between S. pogona-fcl and S. pogona. Aboved all showed that deletion of fcl gene in S. pogona hindered the growth and development of mycelia, but was beneficial to increase the biosynthesis of butenyl-spinosyn and improve insecticidal activity. Whereas the fcl gene over-expression was not conducive to the biosynthesis of butenyl-spinosyn and reduced their insecticidal activity. SDS-PAGE results showed that the difference of protein expression among the three strains was most obvious at 96 hours, which was identified by real-time fluorescence quantitative polymerase chain reaction, the results showed that there were significant differences of related genes in transcriptional levels among the three strains. Based on the results of the study, a network metabolic control map was constructed to analyze the effect of fcl gene on growth and the regulation pathway of butenyl-spinosyn biosynthesis, which provided an experimental basis for revealing the regulation mechanism of butenyl-spinosyn biosynthesis and related follow-up studies.
Bacterial Proteins ; Genetic Engineering ; Insecticides ; Macrolides ; Saccharopolyspora

Objective To investigate the clinical effect on incomplete spinal injury by ganglioside intravenous injection combined with intrathecal injection.Methods From January 2011 to January 2015, seventy-nine cases with irreducible articular process interlocking of cervical spine fracture with dislocation of cervical spinal cord injury,underwent one stage anterior and posterior surgical treatment,postoperative routine use of antibiotics to prevent infection,and the hormone,dehydration to promote bone cell growth and neurotrophic drugs treatment.The patients were randomly divided into the intravenous injection group(42 cases),given intravenous injection of monalsialic acid four hexose ganglioside sodium(GM-1)40 mg/d,mecobalamin tablets 0.5 mg/time,3 times/d,30 d oral;the combined intrathecal injection group(37 cases)was given GM-1 40 mg/d,intravenous injection at 15 d after intrathecal injection,1 time a week 40 mg,with a total of 4 weeks.The degree of spinal cord injury was evaluated according to Frankel classification; cervical function was evaluated according to JOA score; bone graft fusion,stability of cervical spine and degree of spinal cord injury were evaluated by imaging.Results The operation time in the intravenous injection group and the combined intrathecal injection group were(4.15 ± 0.65)h and(4.10 ± 0.85)h,and the intraoperative blood loss was(850.50±35.10)ml and(858.60±25.20)ml,respectively,and there were no significant differences between the two groups(t=1.375,1.452,P>0.05).The total dose of GM-1 in the combined intrathecal injection group was(785.20 ± 3.28)mg,significantly higher than that in the intravenous injection group((610.55 ± 5.28) mg),the difference was statistically significant(t=12.542,P<0.05);79 patients were followed up for 12-24 months,with an average of(15.2 ± 1.3)months.The improvement rate of nerve function of the combined intrathecal injection group was(64.35±4.33)%,significantly higher than that in the intravenous injection group (55.50±5.44)%,the difference was statistically significant(t=8.813,P<0.05);the postoperative JOA scores of the intravenous injection group((13.55 ± 1.75)points)and combined intrathecal injection group((12.85 ±1.97)points)were significantly higher than those before the surgery((7.25± 0.83)points,(7.19± 0.93) points),the differences were statistically significant(P<0.05).There was no significant difference in the JOA scores between the two groups before and after the operation(P>0.05).At the last follow-up,X-ray showed bone fusion at the bone graft site,and the internal fixation was good and firm.MR showed that the degeneration signal area of the cervical spinal cord decreased in varying degrees,and edema and inflammatory reaction disappeared.Conclusion Postoperative treatment of ganglioside intravenous injection combined with intrathecal injection is safe and feasible in the treatment of incomplete cervical spinal cord injury caused by cervical fracture dislocation with irreducible articular process interlocking.