Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00～0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01～0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08～2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.

Objective:To explore the value of quantitative parameters of cortical and cancellous bone in the first lumbar vertebrae (L1) based on CT spinal bone quantification system for evaluating the severity of chronic obstructive pulmonary disease (COPD) in males.Methods:A total of 88 male patients with COPD diagnosed at the Second Affiliated Hospital of Shandong First Medical University from August 2021 to December 2022 were retrospectively analyzed. According to the 2023 edition of global initiative for chronic obstructive lung disease (GOLD), the patients were classified as GOLD Ⅰ (29 cases), GOLD Ⅱ (36 cases), and GOLD Ⅲ-Ⅳ (23 cases). And then 29 males with normal lung function during the same period were recruited. People with normal lung function and COPD patients of GOLD Ⅰ-Ⅱ were classified as non-severe COPD group (94 cases), COPD patients of GOLD Ⅲ-Ⅳ were classified into the severe COPD group (23 cases). On the CT images of L1, the CT spine bone quantification system was used to automatically segment cortical and cancellous bone. The total volume, cortical volume, cancellous volume, average cortical thickness, cortical bone average CT value and cancellous bone average CT value of L1 vertebral body were measured using the system respectively. Single factor analysis of variance was used to compare the differences of various parameters among normal lung function and COPD patients with different lung function grades. The efficacy of various parameters in evaluating the severity of COPD were calculated using the receiver operating characteristic curve.Results:The overall differences in L1 vertebral total volume, cancellous volume and cortical bone average CT value among people with normal lung function and COPD patients of GOLD Ⅰ, Ⅱ, and Ⅲ-Ⅳ were statistically significant ( F=3.60, 4.26, 5.39, P=0.016, 0.007, 0.002), and showed a downward trend as the severity of COPD progressed. There were no statistically significant difference in cortical volume, average cortical thickness and cancellous bone average CT value of L1 ( P>0.05). The area under the curve (AUC) for distinguishing severe and non-severe COPD was 0.64 (95%CI 0.54-0.72), 0.65 (95%CI 0.56-0.74) and 0.75 (95%CI 0.66-0.83) for the total vertebral volume, cancellous volume and cortical bone average CT value of L1 respectively. The AUC of cortical bone average CT value was the highest, with a cutoff value of 217 HU/mm 3, a sensitivity of 69.6% and a specificity of 80.9%. Conclusion:Male COPD patients have reduced bone mass compared to the same age male population. The L1 quantitative parameters measured based on the CT spinal bone quantification system can effectively evaluate the severity of lung function in male COPD patients. Among them, the cortical bone average CT value has the highest diagnostic efficacy.

Objective To explore the therapeutic effect of lignans extracted from Eucommia Ulmoides Oliver on diabetes encephalopathy(DE)rats and the effects on nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods A rat model of DE was established,and 48 successfully established DE rats were randomly divided into model group,and low-and high-dose lignans groups(200 and 400 mg/kg),and metformin(200 mg/kg)group,with 12 rats in each group.Another 12 healthy rats served as control group.Each group of rats was giv-en corresponding drug intervention once a day for 6 consecutive weeks.Cognitive and memory abilities,serum levels of IL-6,TNF-α,MDA and SOD,and mRNA and protein levels of Nrf2 and HO-1 in the hippocampus were measured in all groups.Pathological changes of the hippocampus were observed after HE staining.Results Compared with the control group,significantly longer escape latency and increased serum levels of IL-6,TNF-α and MDA,while lower times of crossing original platform,shorter residence duration of original platform quadrant,decreased serum SOD level,and reduced mRNA and protein levels of Nrf2 and HO-1 in the hippocampus were observed in the model group(all P＜0.05).Low-and high-dose lignans treatment reversed all above indica-tors when compared with model group(P＜0.05).What's more,the effects of high-dose lignans treatment were more significant than low-dose treatment in escape latency,serum levels of IL-6,TNF-α and MDA,times through the original platform,residence duration of the original platform quadrant,serum SOD level,and mRNA Nrf2 and HO-1 in the hippocampus(6.07±0.70 vs 4.76± 0.52,30.96±2.96 s vs 23.49±2.60 s,77.02±6.51 U/ml vs 61.71±6.75 U/ml,0.69±0.06 vs 0.49± 0.05,0.74±0.07 vs 0.57±0.06,P＜0.05).Conclusion Eucommia lignans can improve the cogni-tive ability,enhance the antioxidant capacity,inhibit inflammatory response and protect the hippo-campus of DE rats,and the mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.

Penicillins are one type of the most important antibiotics used in the clinic.Control of drug impurity profiles is an important part of ensuring drug safety.This is particularly important in penicillins where polymerization can lead to polymers as elicitors of passive cutaneous anaphylaxis.The current under-standing of penicillin polymerization is based on reactions with amino groups,but no comprehensive mechanistic understanding has been reported.Here,we used theoretical calculations and column switching-LC/MS techniques to study penicillin dimerization.Ampicillin and benzylpenicillin were selected as representative penicillins with or without amino groups in the side chain,respectively.We identified four pathways by which this may occur and the energy barrier graphs of each reaction process were given.For benzylpenicillin without an amino group in the 6-side chain,dimerization mode A is the dominant mode,where the 2-carboxyl group of one molecule reacts with the β-lactam of another molecule.However,ampicillin with an amino group in the 6-side chain favors dimerization mode C,where the amino group of one molecule attacks the β-lactam of another molecule.These findings can lead to a polymer control approach to maintaining penicillin antibiotics in an active formulation.

Objective:To analyze the effect of continuing care in patients treated with endonasal endoscopic conjunctivorhinostomy, so as to guide its clinical application.Methods:A total of 192 patients were selected with endonasal endoscopic conjunctivorhinostomy who were admitted to the Aier Eye Hospital of Wuhan University from June 2013 to June 2019 as the research objects. Randomized digital table method was used to divide them into control group and observation group, 96 cases in each group. The control group was given routine instructions before discharge, while the patients in observation group were given continuing care intervention on the basis of control group, including establishment of a continuing care group, establishment of health files of discharged patients, regular follow-up through telephone, establishment of WeChat groups for patients or their families, opening WeChat official account, organization of doctor-patient discussion meeting, and setting up reexamination services. The reexamination adherence rate, medication adherence rate, care satisfaction and treatment efficacy were compared between the two groups 6 months after implementation.Results:The reexamination adherence rate of the observation group on 1, 3, and 6 months after discharge were 85.42%(82/96), 96.88%(93/96), 72.92%(70/96), and the control group were 62.50%(60/96), 73.96%(71/96), and 43.75%(42/96), respectively, the difference between the two groups was statistically significant ( χ2 value was 13.088,20.237, 16.800, P<0.05); the medication adherence rate of the observation group was 89.58%(86/96), and the control group was 62.50%(60/96), the difference between the two groups was statistically significant ( χ2 value was 19.326, P<0.05); the observation group's care satisfaction was 94.79%(91/96), the control group was 78.13%(75/96), the difference between the two groups was statistically significant ( χ2 value was 11.388, P<0.05); the total treatment efficacy in the observation group was 96.88%(93/96), and the control group was 87.50%(84/96), the difference between the two groups was statistically significant ( χ2 value was 5.858, P<0.05). Conclusion:The application of continuing care for patients treated with endonasal endoscopic conjunctivorhinostomy can improve patients′ reexamination and medication adherence, improve care satisfaction, promote patients′ good recovery and achieve better surgical effects, which is worthy to recommend its clinical application.

Objective To establish a high performance size esclusion chromatography (HPSEC) method for the determination of high molecular weight impurities of cefotiam hydrochloride for injection.Methods A TSK G2000 SWXL column(7.8 mm × 30 cm,5μm) was used,the mobile phase consisting of phosphate budder solution [0.1 mol·L-1 disodium hyrogen phosphate-0.1 mol·L-1 sodium dihydrogen phosphate (61:39)],the flow rate was 0.7 mL· min-1,the detection wavelength was 254 nm,the column temperature was 30 ℃,the injection volume was 20 μL,and the concentration of polymers was quantified by external standard method.Results For HPSEC method,the calibration curves were linear in the range of 5.0-25.0 μg·mL-1 for cefotiam,and the LOD and LOQ was 0.1 μg·mL-1 and 0.246 μg· mL-1,the RSD for replicate for injections of reference solution was 0.50％,the sample solution was not stable in room temperature.Conclusion The method has high separation efficiency and good specificity,which provides reference for the further study of the polymer of cefotiam hydrochloride for injection.

Objective To determine the safety and clinical value of secondary ERCP to a failed intubation procedure.Methods A total of 212 patients with difficult intubation during ERCP procedures were enrolled.Patients with failed conventional intubation accepted precut sphincterotomy.The operation stopped after one hour of effort.A secondary selective ERCP was performed at a appropriate time.The operation success rate and complication rate of first ERCP and secondary ERCP were compared.Results The success rate of first ERCP was 67.0％ (142/212),and the total success rate was 90.6％ (192/212).The total success rate is significantly higher than that of first ERCP operation(x2 =35.263,P ＜0.05).The complication rate of first ERCP,secondary ERCP and total complication rate was 8.96％ (19/212),4.29％ (3/70),10.38％ (22/212),respectively.Complication rates of total ERCP and secondary ERCP were not significantly different from the first ERCP (P ＞ 0.05).Conclusion It is safe and effective for patients with failed ERCP intubations after precut to receive a secondary ERCP at a appropriate time.

Objective To evaluate the clinical utility of SpyGlass single-operator ERCP-guided cholangiopancreatoscopy system for the diagnosis and treatment of bile duct disorders.Methods A total of 9 patients with biliary diseases were treated with SpyGlass single-operator ERCP-guided cholangiopancreatoscopy system.Four patients with large bile duct stones accepted laser lithotripsy,and stones were removed by ERCP.Five patients with indeterminate bile duct stricture accepted cholangioscopy-guided sampling.All patients underwent ENBD,routine blood test,blood amylase test,oral food and water restriction,acid suppression and prophylactic antibiotics.Results SpyGlass was successful in all patients with a manipulating time of 21.2min and total procedure time of 46.2min.Complete stone clearance was achieved in all 4 patients with large biliary stones.Sample quality was adequate in all patients with bile duct stricture with 2 patients diagnosed as having malignant biliary tumor and 3 as inflammatory bile duct stenosis.Post-ERCP complications including mild pancreatitis in 2 patients,and the patients recovered gradually after corresponding treatment.Conclusion ERCP-guided cholangiopancreatoscopy with the SpyGlass system is technically feasible and can be successfully and safely performed in patients with biliary disorders.

Reference materials containing mixed degradation products of amoxicillin and ampicillin were developed after optimization of preparation processes. The target impurities were obtained by controlled stress testing, and each major component was identified with HPLC-MS and compared with single traceable reference standard each. The developed reference materials were applied to system suitability test for verifying HPLC system performed in accordance with set forth in China Pharmacopeia and identification of major impurities in samples based on retention and spectra information, which have advantages over the methods put forth in foreign pharmacopoeias. The development and application of the reference materials offer an effective way for rapid identification of impurities in chromatograms, and provide references for analyzing source of impurities and evaluation of drug quality.

Reversed-phase liquid chromatography coupled with electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to characterize impurities in cefpodoxime proxetil, an ester-modified prodrug. Based on the mechanisms by which cephalosporins are degraded, stress tests were designed and performed. The bulk material and capsule were eluted through a C18 column with formic acid-methanol-water as the mobile phase. In total, 15 impurities were characterized in commercial samples, including 7 known impurities and 8 new impurities. The structures of these unknown compounds were deduced via comparison with the fragmentation patterns of cefpodoxime proxetil. Data from this systematic study will help improve the safety and quality of cefpodoxime proxetil.