Objective:To evaluate the effect of smoking on the sedative potency of remimazolam combined with alfentanil in patients undergoing painless gastroscopy.Methods:This was a prospecctive single-center study. American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ male patients, aged 30-75 yr, with a body mass index of 18-28 kg/m 2, undergoing elective painless gastroscopy at Baoding First Central Hospital from October to December 2023, were divided into non-smoking group, mild smoking group (smoking index≤200), moderate smoking group (200 1 after 3 min of remimazolam injection or development of bucking, swallowing, body movement and other responses that affected operations during insertion of the endoscope. Results:A total of 85 patients were finally included, with 21 in non-smoking group, 21 in mild smoking group, 20 in moderate smoking group and 23 in heavy smoking group. The ED 50 of remimazolam was significantly higher in smoking groups than in non-smoking group ( P<0.05). The ED 50 of remimazolam gradually increased in mild, moderate and heavy smoking groups ( P<0.05). Conclusions:Smoking can decrease the sedative potency of remimazolam when combined with alfentanil in patients undergoing painless gastroscopy.

Objective:To evaluate the effect of smoking on the sedative potency of remimazolam combined with alfentanil in patients undergoing painless gastroscopy.Methods:This was a prospecctive single-center study. American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ male patients, aged 30-75 yr, with a body mass index of 18-28 kg/m 2, undergoing elective painless gastroscopy at Baoding First Central Hospital from October to December 2023, were divided into non-smoking group, mild smoking group (smoking index≤200), moderate smoking group (200 1 after 3 min of remimazolam injection or development of bucking, swallowing, body movement and other responses that affected operations during insertion of the endoscope. Results:A total of 85 patients were finally included, with 21 in non-smoking group, 21 in mild smoking group, 20 in moderate smoking group and 23 in heavy smoking group. The ED 50 of remimazolam was significantly higher in smoking groups than in non-smoking group ( P<0.05). The ED 50 of remimazolam gradually increased in mild, moderate and heavy smoking groups ( P<0.05). Conclusions:Smoking can decrease the sedative potency of remimazolam when combined with alfentanil in patients undergoing painless gastroscopy.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective:To examine the effect of the "four-steps" treatment on infectious pancreatic necrosis(IPN).Methods:The data of 207 patients who were diagnosed with IPN from January 2013 to December 2017 at Department of Pancreaticobiliary Surgery, the First Affiliated Hospital of Harbin Medical University were analyzed retrospectively. Among 207 patients, 132(63.8%) were males and 75(36.2%) were females. The median age was 45 years old (range: 19 to 80 years old). One hundred and fifty-eight patients(76.3%) suffered severe acute pancreatitis and 49 patients(23.7%) suffered moderately severe acute pancreatitis. Percutaneous catheter drainage(PCD) was performed on all the patients(Step 1). Patients received "four-steps" minimally invasive treatment strategy in step-up group(173 patients). The following steps after PCD were mini-incision access pancreatic necrosectomy(MIAPN) (Step 2), sinus tract endoscopic debridement and(or) PCD for residual infections(Step 3) and finally conventional open pancreatic necrosectomy(OPN) (Step 4). Patients(34 cases) received conventional open pancreatic necrosectomy after invalided PCD in OPN group. The perioperative parameters and prognosis were compared between Step-up group and OPN group. Normally distributed quantitative variables were analyzed by t-test, non-normally distributed quantitative variables were analyzed by Wilcoxon chi-square test and categorical variables were analyzed by χ 2 test or Fisher exact test, respectively. Results:The basic characteristics of the two groups of patients were similar, but the referral rate of patients and the rate of preoperative 3 days organ failure in the OPN group were significantly higher than those of step-up group patients(47.1% vs. 28.9%, χ 2=4.313, P=0.038; 26.5% vs. 9.2%, χ 2=2.819, P=0.011). The frequency of PCD and the number of PCD tube (root) were less than those in the step-up group(1(1) vs. 2(1), Z=-3.373, P=0.018; 2(1) vs. 3(2), Z=-2.208, P=0.027). Compared with the OPN group, the interval time from onset to surgery and the MIAPN operation time were significantly shorter in the step-up group(29(15) days vs. 36(17)days, Z=-0.567, P=0.008; 58(27)minutes vs. 90(56)minutes, Z=-3.908, P<0.01); postoperative mortality was lower(5.8% vs.17.6%, χ 2=4.070, P=0.044); the overall incidence of postoperative complications was reduced(23.1% vs. 55.9%, χ 2=14.960, P<0.01) and the incidence of new-onset organ failure was decreased after operation in the step-up group(37.5% vs.47.4%, χ 2=7.133, P=0.007). The incidence of local abdominal complications (pancreatic fistula, intra-abdominal hemorrhage, gastrointestinal fistula) showed no significant difference between the two groups ( P>0.05). Fewer patients required ICU treatment after operation in the step-up group compared with OPN group(22.0% vs. 44.1%, χ 2=6.204, P=0.013). Patients in the Step-up group has shorter hospital stay than patients in OPN group (46(13) days vs. 52(13)days, Z=-1.993, P=0.046). Conclusions:The clinical effects of "four-steps" exhibited the superiority of minimally invasive treatment of IPN.And MIAPN is a simple, safe and effective procedure to remove pancreatic necrotic tissue and decrease complications.

Objective:To examine the effect of the "four-steps" treatment on infectious pancreatic necrosis(IPN).Methods:The data of 207 patients who were diagnosed with IPN from January 2013 to December 2017 at Department of Pancreaticobiliary Surgery, the First Affiliated Hospital of Harbin Medical University were analyzed retrospectively. Among 207 patients, 132(63.8%) were males and 75(36.2%) were females. The median age was 45 years old (range: 19 to 80 years old). One hundred and fifty-eight patients(76.3%) suffered severe acute pancreatitis and 49 patients(23.7%) suffered moderately severe acute pancreatitis. Percutaneous catheter drainage(PCD) was performed on all the patients(Step 1). Patients received "four-steps" minimally invasive treatment strategy in step-up group(173 patients). The following steps after PCD were mini-incision access pancreatic necrosectomy(MIAPN) (Step 2), sinus tract endoscopic debridement and(or) PCD for residual infections(Step 3) and finally conventional open pancreatic necrosectomy(OPN) (Step 4). Patients(34 cases) received conventional open pancreatic necrosectomy after invalided PCD in OPN group. The perioperative parameters and prognosis were compared between Step-up group and OPN group. Normally distributed quantitative variables were analyzed by t-test, non-normally distributed quantitative variables were analyzed by Wilcoxon chi-square test and categorical variables were analyzed by χ 2 test or Fisher exact test, respectively. Results:The basic characteristics of the two groups of patients were similar, but the referral rate of patients and the rate of preoperative 3 days organ failure in the OPN group were significantly higher than those of step-up group patients(47.1% vs. 28.9%, χ 2=4.313, P=0.038; 26.5% vs. 9.2%, χ 2=2.819, P=0.011). The frequency of PCD and the number of PCD tube (root) were less than those in the step-up group(1(1) vs. 2(1), Z=-3.373, P=0.018; 2(1) vs. 3(2), Z=-2.208, P=0.027). Compared with the OPN group, the interval time from onset to surgery and the MIAPN operation time were significantly shorter in the step-up group(29(15) days vs. 36(17)days, Z=-0.567, P=0.008; 58(27)minutes vs. 90(56)minutes, Z=-3.908, P<0.01); postoperative mortality was lower(5.8% vs.17.6%, χ 2=4.070, P=0.044); the overall incidence of postoperative complications was reduced(23.1% vs. 55.9%, χ 2=14.960, P<0.01) and the incidence of new-onset organ failure was decreased after operation in the step-up group(37.5% vs.47.4%, χ 2=7.133, P=0.007). The incidence of local abdominal complications (pancreatic fistula, intra-abdominal hemorrhage, gastrointestinal fistula) showed no significant difference between the two groups ( P>0.05). Fewer patients required ICU treatment after operation in the step-up group compared with OPN group(22.0% vs. 44.1%, χ 2=6.204, P=0.013). Patients in the Step-up group has shorter hospital stay than patients in OPN group (46(13) days vs. 52(13)days, Z=-1.993, P=0.046). Conclusions:The clinical effects of "four-steps" exhibited the superiority of minimally invasive treatment of IPN.And MIAPN is a simple, safe and effective procedure to remove pancreatic necrotic tissue and decrease complications.

Pancreatic fistula is a common and serious complication after pancreatic surgery. Pancreatic fistula, intra-abdominal infection and hemorrhage are known as the " lethal triad" after pancreatic surgery, which seriously affect the curative efficacy of operation. Although the incidence of pancreatic fistula has not been significantly reduced, there have been a large number of studies on the risk factors of pancreatic fistula and the means of prevention and therapy, which try to minimize the harm of pancreatic fistula. In this article we review the recent development of the latest definition, high risk factors and treatment of postoperative pancreatic fistula according to relevant literatures at home and abroad, aiming at summarizing the research advances on the therapy of pancreatic fistula after pancreatic surgery.

Objective:To investigate the effect of Chinese traditional medicine-Shuanghuangbu combined with Xipayi Mouth Rinse on the periodontal indexes of the peri-implantitis patients,and to detect the curative effect of Shuanghuangbu combined with Xipayi Mouth Rinse in the treatment of peri-implantitis.Methods: A total of 40 patients diagnosed as peri-implantitis were randomly divided into control group and Chinese traditional medicine group (n=20).All of the patients received supragingival scaling and subgingival scaling,and then the peri-implant pocket of the patients in Chinese traditional medicine group were washed with Xipayi Mouth Rinse,while the fine probe slided slowly along the inner wall of peri-implant pocket into the bottom and retained the Shuanghuangbu,and retreated gently and made the medicine overflow the gingival margin.The patients in control group were given 3% hydrogen peroxide and 0.9% sodium chloride injection washed by turns.The indexes of covering modified plaque index (mPLI),probing pocket depth (PPD),modified sulcular bleeding index (mSBI)of the patients in two groups at baseline and after treatment were detected;Whatman# 1 was applied to aspirate the peri-implant sulcus fluid (PISF)which were weighed at baseline and after treatment,and the level of interleukin-1β (IL-1β)in PISF was analyzed by ELISA method.Results:No differences were observed in age,sex,periodontal indexes, weights of PISF and IL-1βlevels of the patients in two groups before treatment (P >0.05).Compared with before treatment,the indexes including PPD,mSBI,mPLI,weight of PISF and IL-1βlevel in PISF of the patients in two groups were decreased after treatment (P < 0.05).After treatment,the differences in mSBI,mPLI,weight of PISF and IL-1β level in PISF of the patients between control group and Chinese traditional medicine group were significant (P <0.05).Compared with control group,the PPD level of the patients in Chinese traditional medicine group was decreased,but the difference was not significant (P >0.05).Conclusion:The curative effect of Chinese traditional medicine-Shuanghuangbu combined with Xipayi Mouth Rinse is obsious,and the treatment can improve the periodontal status and reduce the level of IL-1βin PISF.

Objective:To use polylactic-co-glycolic acid(PLGA) as vector material to prepare the compound total flavonoids of Rhizoma Drynariae(TFRD) and total flavonoids of Chrysanthemum(TFC) sustained release microcapsule TF-PLGA microcapsules,and to investigate the the best preparation technique of TF-PLGA microcapsules and their sustained release characteristics in vitro.Methods:The TF-PLGA microcapsules were prepared with TFRD,TFC,and PLGA by emulsifying-solvent evaporation technique under certain conditions.With the encapsulation efficiency(EE) as the evaluation indicator,the optimal formulation was verified by single factor experiment and orthogonal design;the general morphology,the particle size and distribution of the microcapsules were observed by light microscope(LM) and scanning electron microscope(SEM);the cumulative drug release rate of TF-PLGA microcapsules was detected by constant temperature commotion method in vitro and the release curves of the TF-PLGA were drawn.Results:The optimal prescription was as follows:the concentration of PLGA was 140 g·L-1,oil phase volume was 1.4 mL,emulsifying speed was 900 r·min-1,emulsifying time was 5 min,the average EE was(83.89±2.30)%,and the average drug loading rate(DL) was(5.90±0.07)%.The LM and SEM resluts showed that the TF-PLGA microcapsules presented as round ball,the average particle size was(44.34±14.68)μm,and the distribution was relatively narrow.The drug release in vitro results showed that the initial drug release rate(24 h)was about 40%,and the cumulative drug release rate was over 90% after 50 d.Conclusion:The TF-PLGA sustained release microcapslue has better drug-loaded and sustained-release effects with simple preparation technique and better repeatability.

The HPLC fingerprint differences ofRadix Platycodonis from different origins were studied to provide references for their quality control and production. The total platycodins were purified by DB101 macroporous resin. HPLC-ELSD fingerprints of the total platycodins for 39 batches ofRadix Platycodonis samples from 9 provinces were performed on an Agilent HC-C8 column (4.6 mm x 250 mm, 5μm) with gradient elution. The mobile phase was acetonitrile-0.5% acetic acid. The injection volume was 6μL. The flow rate was 0.5 mL·min-1. The temperature of drift tube was set at 90℃. And the gas flow (N2) was set at 1.2 mL·min-1. The results showed that there were large differences in the quality ofRadix Platycodonis from different origins with the common fingerprints of 6 batches of samples fromChifeng in Inner Mongolia as references. The quality ofRadix Platycodonis was closely related to the seeds, the ecological environment, the way of drying and storing and so on. It was concluded that it was important to strengthen the provenance base construction, standardization of the seeds, reasonable formulation of the regionalization, and standardization of the production processing for the cultivation and production ofRadix Platycodonis.