ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

PI3K/AKT/mTOR signaling pathway plays a crucial role in cell proliferation, survival, differentiation, motility and intracellular transport. PI3Kδ, an isoform of PI3K, is highly expressed in B lymphocytes and is involved in the malignant progression of B-cell lymphoma. Thus, PI3Kδ has emerged as an attractive target for the development of anti-B-cell lymphoma drugs. Currently, there are several PI3Kδ inhibitors approved by the FDA for the treatment of B-cell lymphoma, each with its own characteristics, but also with varying degrees of adverse effects in clinical practice. Due to the complexity and diversity of the pathogenesis of B-cell lymphoma, single-target PI3Kδ inhibitors often have limited efficacy and are prone to drug resistance, and need to be combined with chemotherapy or other targeted drugs to enhance their efficacy. The future trend is to design novel inhibitors with higher efficacy and lower toxicity or to develop novel combination regimens with other chemotherapy, radiotherapy, and target drugs to acquire better anti-tumor effects with reduced adverse effects. This review summarizes the PI3Kδ inhibitors that have been approved for the treatment of B-cell lymphoma or are still in clinical trials, mainly focusing on their characteristics, adverse effects and combination regimens.

Objective:To explore the early coagulation function changes of penetrating intestinal firearm injury of pig in high-altitude environments.Methods:Twenty healthy long white piglets were selected and divided into the plain group and the high-altitude group using the random number table method, with 10 pigs in each group. Pigs in the plain group were placed in a plain environment at an altitude of 800 meters, while pigs in the high-altitude group were placed in an experimental chamber simulating an altitude of 6 000 meters for 48 hours. Both groups received pistol gunshot to have firearm penetrating wounds to the abdominal intestinal tract and then returned to the plain observation room. At 0, 2, 4, 8, 12 and 24 hours after injury, coagulation in the peripheral blood and fibrinolytic indexes [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fbg), D-dimer (D-D), and fibrinogen degradation product (FDP)], thromboelastogram (TEG) [reaction time (R), clotting time (K), clot formation rate (α), maximum amplitude (MA) and coagulation composite index (CI) ], platelet parameters [platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio (P-LCR)] in the two groups were detected separately.Results:The PT values at 0 and 2 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours than those in the plain group ( P<0.01); there was no significant difference at 4 hours between the two groups ( P>0.05). The APTT values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The TT values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.01); there was no significant difference at 8 hours after injury between the two groups ( P>0.05). The Fbg, D-D and FDP values at 0, 2, 4, 8, 12 and 24 hours after injury were higher in the high-altitude group than those in the plain group ( P<0.01). The R values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The K values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The α angles at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The MA values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The CI values at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The PLT values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The MPV values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.01). The PDW values at 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.05 or 0.01), while there was no significant difference in PDW at 0 hour after injury between the two groups ( P>0.05). The P-LCR values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were all significantly higher than those in the plain group ( P<0.01). Conclusion:Compared with the plain environments, pig intestinal firearm penetrating injury in the high-altitude environments is more prone to early hypercoagulable state accompanied by mild hyperfibrinolysis, and faster to reach a hypocoagulable state accompanied by obvious hyperfibrinolysis.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients'orthodontic treatment.

Objective:To explore the challenges in the implementation of drug centralized volume-based procurement policies in hospitals and propose corresponding optimization suggestions.Methods:From August to December 2023, a purposive sampling was conducted to select 11 pharmaceutical experts from tertiary hospitals in China for Delphi method. The survey content included " policy recommendations for promoting the acceleration and expansion of national drug centralized procurement and retaining surplus medical insurance funds for centralized procurement" .Results:Survey participants gave feedback on a set of existing problems found in the implementation of drug centralized procurement policies and proposed corresponding optimization methods. Kendall′s W coefficient of the specialist consultation was 0.332( P<0.05), demonstrating good consistency and concentration of the expert opinions. Among the problems, the score of drug supply guarantee was the highest(mean value of importance was 4.45). At the same time, the recommendation of strengthening monitoring and early warning, coordination and dispatch, and effectively ensuring the supply of centralized drug procurement had the highest score and concentration(mean value of importance was 4.91, coefficient of variation was 0.06). Conclusions:Through Delphi method, this study revealed issues and optimization methods in the implementation of drug centralized procurement policies in hospitals. The findings could provide valuable insights for improvements in the pharmaceutical sector and future policy adjustments.

Objective To analyze the correlations of D-dimer and the Global Registry of Acute Coronary Events (GRACE) score with long-term heart failure (HF) in patients with acute myocardial infarction (AMI). Methods A total of 398 patients with AMI were selected as research objects and divided into normal D-dimer group (n=309) and elevated D-dimer group (n=89) based on the D-dimer level. Cox proportional hazard model was used to analyze the risk factors for long-term HF in both groups. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the values of D-dimer, GRACE score and their combination in predicting long-term HF. According to the GRACE score and D-dimer level, 398 patients were divided into low-value group (181 patients with normal D-dimerand low GRACE score), high-value group (70 patients with elevated D-dimer and high GRACE score), and middle-value group (147 patients did not meet the conditions of the low-value and high-value groups). Kaplan-Meier method was used to analyze the occurrence of long-term HF in the three groups. Point-biserial analysis was used to analyze the correlation between elevated D-dimer and the occurrence of long-term HF. Results The number of patients with long-term HF in the elevated D-dimer group was 2.3 times of the normal group. D-dimer and GRACE score were independent risk factors for long-term HF in patients with AMI (P < 0.05). Both D-dimer and GRACE score had certain predictive values for the occurrence of HF at 5 years after AMI, but the predictive efficiency of GRACE score was better. The incidence of long-term HF in the high-value group was significantly higher than that in the low-value group and the middle-value group (P < 0.01). D-dimer was significantly positively correlated with the occurrence of long-term HF after AMI (P < 0.001). Conclusion Both D-dimer and GRACE score are independent risk factors for long-term HF in patients with AMI, and the two indexes have certain predictive value for the occurrence of long-term HF. Patients with both elevated indicators are high-risk groups for long-term HF.

Objective This paper summarizes the research progress of biosynthesis and pharmacological effects of podophyllotoxin drugs,in order to provide reference for the wide application of these drugs.Methods The plant source,chemical structure,action mechanism and synthesis pathway of podophyllotoxin drugs were summarized.The pharmacological and toxicological characteristics and mechanisms of these drugs were discussed,and the research progress of new dosage forms of podophyllotoxin drugs was reviewed.Results Podophyllotoxin and its derivatives are important chemical constituents in the plants of the podophyllum,such as Dysosma versipellis,Diphylleia sinensis,Sinopodophyllum hexandrum.This kind of drug has few natural sources and can be artificially produced through chemical and biosynthetic pathways.Podophyllotoxin drugs have pharmacological effects such as anti-inflammatory,anti-tumor and anti-virus,but their toxic effects need to be paid attention to.Drugs can be transported by carriers to reduce toxicity and increase effect.Conclusion Podophyllotoxin drugs have broad clinical application prospects,and will be further studied and applied in the fields of anti-inflammatory,anti-tumor and anti-virus in the future.

Objective:To investigate the influencing factors of reflux esophagitis after sleeve gastrectomy and its plus procedures.Methods:The retrospective case-control study was conducted. The clinical data of 130 patients who underwent sleeve gastrectomy and its plus procedures (jejunal bypass, duodenal-jejunal bypass) for the treatment of metabolic diseases in the First Affiliated Hospital of Nanjing Medical University from May 2010 to August 2021 were collected. There were 34 males and 96 females, aged (32±8)years, with the body mass index (BMI) as (38±7)kg/m 2. Observation indicators: (1) incidence of reflux esophagitis before and after surgery; (2) clinical manifestations of reflux esophagitis and treatment; (3) influencing factors of reflux esopha-gitis after surgery; (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. In univariate analysis, the median value of clinical variable was used for grouping and the chi-square test was used for subsequent analysis. Multivariate analysis was conducted using Logistic stepwise regression model. Results:(1) Incidence of reflux esophagitis before and after surgery. Of 130 patients, there were 5 cases with Los Angeles classification grade A reflux esopha-gitis before the surgery, and there were 35 cases with reflux esophagitis after surgery, including 26 cases as Los Angeles classification grade A esophagitis, 8 cases as Los Angeles classification grade B esophagitis and 1 case as Los Angeles classification grade C esophagitis. There was a significant difference in the incidence of reflux esophagitis for patients before and after surgery ( P<0.05). (2) Clinical manifestations of reflux esophagitis and treatment. The 5 patients with preoperative reflux esophagitis described with no obvious heartburn and acid regurgitation and did not receive treat-ment. For the 35 patients with postoperative reflux esophagitis, 22 cases described with heartburn and acid regurgitation, and 13 cases described without any symptoms. Of the 35 patients, 10 were treated with continuous oral proton pump inhibitors, 2 were treated with intermittent oral proton pump inhibitors, 10 were relieved by dietary adjustment, and 13 were not treated. For the 95 patients without postoperative reflux esophagitis, 5 cases described with heartburn and acid regurgitation, requiring continuous oral proton pump inhibitor treatment. The remaining 90 cases described no heartburn and acid regurgitation and did not receive treatment. (3) Influencing factors of reflux esophagitis after surgery. Results of multivariate analysis showed that the preoperative reflux diagnostic questionnaire scoring >0 and the occurrence of postoperative heartburn and acid regurgi-tation were independent risk factors of postoperative reflux esophagitis ( odds ratio=7.84, 47.16, 95% confidence interval as 2.04?30.20, 11.58?192.11, P<0.05). (4) Follow-up. All 130 patients were followed up for 17(range, 12?60)month after surgery. The BMI, percentage of total weight loss, diabetes remission rate, fasting blood glucose and glycosylated hemoglobin of the 130 patients at postoperative 12 month were (25±4)kg/m 2, 31%±8%, 84.6%(22/26), (5.6±1.2)mmol/L and 5.9%±1.3%. Conclusions:The sleeve gastrectomy and its plus procedures increase the risk of postoperative reflux esophagitis. Preoperative reflux diagnostic questionnaire scoring>0 and the occurrence of postoperative heartburn and acid regurgitation are independent risk factors of postoperative reflux esophagitis. Dietary adjustment and proton pump inhibitor therapy can alleviate symptoms of reflux esophagitis, but cannot cure reflux esophagitis.

Objective:To compare the clinical efficacy of percutaneous transhepatic gallbladder drainage (PTGBD) combined with delayed laparoscopic cholecystectomy (LC) with direct LC in the treatment of acute cholecystitis.Methods:A single-center case-control retrospective study was used. Sixty-three patients with acute cholecystitis with onset time ≥ 72 hours during the period from August 1, 2021 to December 10, 2022 in the Department of Hepatobiliary Surgery of the 900TH Hospital of Joint Logistics Support Force were selected. There were 38 males and 25 females, aged (57.3±15.4) years, with an age range of 28-87 years. According to whether PTGBD treatment was performed before LC, they were divided into experimental group ( n=29) and control group ( n=34). Experimental group was treated with PTGBD combined with delayed LC and control group was treated with LC only.The differences in operative time, intra-operative bleeding, intra-operative transit open rate, post-operative hospital days, total hospital days, hospital costs, short-term post-operative complications of LC and post-operative time to exhaustion were compared and analysed between the two groups. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and independent sample t-test was used for comparison between groups.Measurement data with skewed distribution were expressed as M( Q1, Q3), and rank sum test was used for comparison between groups; Chi-square test was used to compare the counting data groups. Results:Intraoperative bleeding, total hospital days, hospital costs and postoperative time to exhaustion were 0(0, 50) mL, 13(11, 18) d, 29 015.0 (22 791.6, 39 000.8) yuan and 1(1, 2) d in the experimental group and 50(0, 88) mL, 7(6, 11) d, 16 015.0 (15 832.1, 22 185.1) yuan, 2(1, 3) d, the difference was statistically significant between the two groups( P<0.05). In the experimental group, the operative time, the intraoperative transit open rate, the number of postoperative hospital days, and the incidence of short-term postoperative complications of LC were 80 (55, 115) min, 13.8%, 5 (3, 7) days, 34.5%, respectively, compared with 98(70, 125) min, 20.6%, 5(3, 6) days, 38.2% in the control group, the difference between the two groups was not statistically significant ( P>0.05). Conclusion:The clinical efficacy of PTGBD combined with delayed LC is better than direct line LC, and it is feasible and effective for patients with cholecystitis whose inflammatory indexes have returned to normal and who have high gallbladder tone.

Klebsiella pneumoniae is one of the common pathogens causing hospital-acquired infection. With the wide use of carbapenem in recent years, carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged around the world. Carbapenemase production is the main cause of resistance to carbapenem antibiotics in Klebsiella pneumoniae. More than 70% of Klebsiella pneumoniae strains produce carbapenemase. Ceftazidime/avibactam (CAZ/AVI) can effectively treat CRKP infection, especially those caused by CRKP that can produce Klebsiella pneumoniae carbapenemase (KPC) or oxaclillinase (OXA)-48. However, it has been reported that CAZ/AVI-resistant CRKP strains have emerged. In this paper, the epidemiology, risk factors, resistance mechanism and treatment of CAZ/AVI-resistant CRKP were summarized to provide reference for clinical treatment.