Objective To investigate the necessity of further surgery for patients with locally advanced esophageal squamous cell carcinoma following treatment with the programmed cell death-1 (PD-1) inhibitor combined with chemotherapy, and to assess its impact on survival. Methods Patients with stage ⅡA to ⅢB esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at our hospital from January 2020 to June 2022 were selected for this study. Based on whether they underwent surgery after receiving PD-1 inhibitor combined with chemotherapy, patients were divided into a surgery group and a non-surgery group. We compared the general clinical data, side effects, clinical complete response rates, progression-free survival (PFS), and overall survival (OS) between the two groups. Results A total of 58 patients were included in the study, comprising 45 males and 13 females, with an average age of (65.5±6.9) years. There were no statistical differences in general clinical data or adverse reactions between the two groups. Univariate analysis revealed that the objective response rate and surgery were significantly associated with PFS (P<0.05). Binary logistic regression analysis showed that surgery was the only independent risk factor for PFS (P=0.003). Kaplan-Meier survival analysis showed that the PFS and OS in the surgery group were significantly higher than those in the non-surgery group (HR=0.13, 95%CI 0.036 to 0.520, P＜0.001; HR=0.17, 95%CI 0.045 to 0.680, P=0.004). Conclusion After treatment with the PD-1 inhibitor combined with chemotherapy, patients with locally advanced esophageal squamous cell carcinoma still require surgical intervention to achieve improved PFS and OS.

Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.

Surgery is the preferred treatment for resectable esophageal cancer, but in locally advanced esophageal cancer, the effect of surgery alone is not ideal, so surgery-based comprehensive treatment is the best option. Neoadjuvant therapy has become a standard treatment in the treatment of locally advanced resectable esophageal cancer. Neoadjuvant therapy includes neoadjuvant chemotherapy, radiochemotherapy, immunotherapy, targeted therapy, etc. With the significant efficacy and acceptable toxicity of immunotherapy in the first-line and second-line treatment of advanced esophageal cancer, neoadjuvant immunotherapy has become a research hotspot of locally advanced resectable esophageal cancer. This article reviews the latest research progress and some limitations of neoadjuvant immunotherapy in locally advanced resectable esophageal cancer.

Objective: The rate of drug craving not only in Pakistan is escalating rapidly, but also from a wide range of cultures and geographically have been impacted by the drug problem. Recently, drug cravings among young Pakistani school and college students have significantly increased, particularly illegal substances like hashish, heroin, and ecstasy. Methods: We recruited 338 students and gathered demographic and drug-craving data through a survey. To assess the study variables, we used the parental acceptance-rejection short version, peer pressure questionnaire, and adult personality assessment scale. Results: The prevalence rate of occasional drug craving was 44.1% (tobacco, 39.9%; heroin, 1.8%; ice, 0.6%; and others), and 55.9% have never tried them. Initially, drug craving at the first onset at the age of 14 in friend gatherings (15.7%) in stressful situations (11.2%), high-income families, particularly in joint family systems with paternal rejection, peer enforcement, and maladjustment had a higher risk than affectionate parents and conventional peers. Stepwise binary logistic regression analysis disclosed that age, socioeconomic status, father affection, hostility, rejection, negligence, peer influences, and psychosocial adjustment, mother hostility were independently associated with occasional drug cravings. Conclusion Findings suggested the high prevalence of occasional drug cravings in Pakistani students in the capital territory. Furthermore, the demographic and other social and clinical aspects could be linked. This study carried out theoretical significance in understanding the predictors of occasional drug craving and psychological adjustment, highlighting the peer and parent’s roles and the educational institutions.

Objective:To analyze the mortality of accidental falls among the elderly in China from 2004 to 2019 and predict the standardized mortality from 2020 to 2024, so as to provide scientific evidence for formulating strategies to prevent accidental falls among the elderly.Methods:The death data of accidental falls of the elderly in China from 2004 to 2019 were collected from the China Death Cause Monitoring Data Set, and the total number of deaths, mortality rate and standardized mortality rate in the elderly from 2004 to 2019 and those data among them of different genders, residences and age groups were calculated. Joinpoint 4.8.0.1 statistical software was used to calculate the annual percent change (APC) and average annual percent change (AAPC) of standardized mortality. The Autoregressive Integrated Moving Average Model (ARIMA) was used to predict the standardized mortality rate of accidental falls among the elderly in China from 2020 to 2024. Results:The number of deaths related to accidental falls among the elderly in China was increased from 2 908 in 2004 to 23 709 in 2019. The mortality rate was increased from 51.89/100 000 in 2004 to 67.74/100 000 in 2019. The standardized mortality rate of accidental falls showed an overall upward trend from 2004 to 2019 (AAPC=1.65, P>0.05), including an upward trend from 2004 to 2010 (APC=1.66, P>0.05), a downward trend from 2010 to 2013 (APC=-9.67, P>0.05), and another upward trend from 2013 to 2019 (APC=7.83, P<0.01). The number of death and mortality rate related to accidental falls in Chinese elderly males and females both showed upward trends from 2004 to 2019, and the standardized mortality rate also showed upward trends from 2004 to 2019 (AAPC males=2.19, AAPC females=0.29, all P>0.05). The standardized mortality rate in males was generally higher than that in females, with that of males showing an upward trend from 2013 to 2019 (APC=7.36, P<0.05) and that of female showing an upward trend from 2014 to2019 (APC=6.92, P>0.05). The number of deaths and mortality rate among the elderly living in rural and urban areas both showed upward trends from 2004 to 2019, and the standardized mortality rate also showed an upward trend from 2004 to 2019 (AAPC rural = 1.71, AAPC urban =1.00, all P>0.05). The standardized mortality rate among the elderly living in rural areas was generally higher than that in urban areas. The rural and urban elderly both showed upward trends from 2013 to 2019 (APC rural = 8.24, APC urban =6.11, all P<0.05). The number of death and mortality rate of different age groups all showed upward trends from 2004 to 2019. The standardized mortality rates of the elderly aged 65-74 years and ≥85 years also showed upward trends from 2004 to 2019 (AAPC 65-74 years=0.38, AAPC ≥ 85 years=4.09, all P>0.05). The standardized mortality rate of the elderly aged 75-84 years showed a downward trend from 2004 to 2019 (AAPC=-0.10, P>0.05), and that of the elderly aged 65-74 years showed an upward trend from 2010 to 2019 (APC=5.35, P<0.05). The standardized mortality rate of the elderly aged 75-84 years and ≥85 years showed upward trends from 2013 to 2019 (APC 75-84 years=6.49, APC ≥ 85 years=10.47, all P<0.05). The ARIMA prediction results showed that the overall standardized mortality rates of accidental falls in the elderly in China from 2020 to 2024 were 69.11/100 000, 72.33/100 000, 74.41/100 000, 76.34/100 000, and 76.48/100 000, respectively, showing a slow upward trend. Conclusions:The accidental fall-related mortality among the elderly in China showed an overall upward trend from 2004 to 2019, and the standardized mortality rate from 2020 to 2024 also shows an upward trend. The elderly who are male in gender, live in rural areas, or at age of ≥85 years are the key population for prevention and control of accidental fall. Active and effective measures should be taken to reduce accidental falls in the elderly so as to contribute to active and healthy aging.

Sepsis is a systemic inflammatory syndrome induced by infection and other factors， with the number of patients worldwide exceeding 10 million each year. The pathophysiological mechanism is of this disease complex. Sepsis is often accompanied by endotoxin translocation， gastrointestinal dysfunction， inflammatory cytokine activation， immune dysregulation， coagulation disorder， multiple organ function impairment and many other body imbalances， as well as systemic inflammation， apoptosis， oxidative stress injury and other cell damage mechanisms. This disease causes a heavy medical burden due to the difficult diagnosis and treatment and the poor prognosis. Great progress has been achieved in the diagnosis and treatment of sepsis with traditional Chinese medicine （TCM） and western medicine. The value of western medicine in the diagnosis and treatment of sepsis is limited due to antibiotic resistance， hormone abuse， and high medical costs. Sepsis is classified as a warm disease or typhoid fever in TCM. Da Chengqitang is a classical formula in the Treatise on Typhoid Fever to deal with the excess syndrome of Yang brightness Fu-organ. Modern medicine has proved that Da Chengqitang has the effect of inhibiting oxidative stress， reducing inflammation， and delaying apoptosis by improving gastrointestinal dynamics and regulating intestinal microecology. On the basis of the previous theoretical basis and the rich experience in the medication， medical practitioners have proposed a new therapeutic concept of using Da Chengqitang in combination with western drugs from a holistic view involving both bacteria and toxicity for treating both the symptoms and the root cause， which has a wide range of application. The article reviews the classical research and latest findings of Da Chengqitang in the treatment of sepsis， with a view to clarifying the mechanism and advantages of this formula in the adjuvant treatment of sepsis， exploring its potential efficacy， and providing timely， adequate， and scientific theoretical support for the promotion of this formula in the clinical practice.

Dioscoreae Rhizoma formula granules are made from decoction pieces by decocting， extracting， separating， concentrating， drying and granulating， which have the advantages of simple dispensing， convenient use and easy to take without decoction. However， because Dioscoreae Rhizoma is rich in starch and mucus components， its extract powder and formula granules are poorly soluble and difficult to dissolve or disperse completely within 5 min， and the insoluble material is difficult to dissolve completely even after 24 h in water， which affects the quality evaluation of the formula granules and medication psychology of patients. Therefore， by studying the dissolution process and mechanism of Dioscoreae Rhizoma extract and its formula granules， it was found that the special chemical composition of Dioscoreae Rhizoma， the denaturation of starch and its compounding with protein and other substances during the high temperature extraction process， and the contraction of coating membrane during the spray drying process were combined to form the special microstructure of coating membrane covering starch granules， and it is the root cause of poor solubility of Dioscoreae Rhizoma formula granules. Based on the research on the structure， property and function of the powder， this paper proposed a technical strategy to improve the solubility of Dioscoreae Rhizoma formula granules by powder modification process， and experimentally demonstrated that the modified Dioscoreae Rhizoma formula granules could completely dissolve within 2 min， which solved the technical problem and could provide reference for the improvement of solubility of other similar varieties， and promote the high-quality development of traditional Chinese medicine formula granule industry.

Background: At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous. Objectives: This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens. Methods: Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10).DFS was administered orally at 10 mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology. Results: Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were “protein processing in endoplasmic reticulum,” “retinol metabolism,” and “glycine, serine, and threonine metabolism.” Conclusions The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.

Objective To explore the effect and safety of enhanced recovery after surgery (ERAS) in the surgical treatment of common bile duct stones.Methods According to random number table,48 patients with common bile duct stones were randomly divided into the ERAS group and the control group.The patients of the control group received the traditional perioperative management and laparotomy exploration of common bile duct.The patients of the ERAS group received the ERAS perioperative management and laparoscopic exploration of common bile duct.The preoperative and postoperative level of C reactive protein (CRP),time to out-of-bed activity,time to food taking,time to anal exsufflation,postoperative hospital stay,hospitalization cost and postoperative complications between the two groups were compared.Results Compared with the control group,the ERAS group had lower levels of CRP on the postoperative 1 day and 3 days[d1:(102.6±13.5) mg/L vs.(81.3±17.3)mg/L;d3:(71.8±15.3)mg/L vs.(41.2±11.2)mg/L,t=2.553,3.287,all P<0.05],had shorter time to out-of-bed activity[(3.2±1.8)d vs.(0.9±0.4)d],time to food taking[(4.3±1.9)d vs.(1.8±1.2)d] and time to anal exsufflation[(2.5±0.7)d vs.(1.2±0.3)d],and had shorter operative hospital stay[(7.3±3.2)d vs.(3.8±1.4)d]and less hospitalization cost[(7 200±800)RMB vs.(5 900±700)RMB] (t=5.561,4.319,3.765,2.351,1.671,all P<0.05).The incidence rate of postoperative complications of the ERAS group decreased markedly (61.91% vs.18.52%,x2=25.82,P<0.05).Conclusion ERAS management in the surgical treatment of common bile duct stones is safe and effective,which can enhance the recovery of the patients.

Objective To investigate the effect of the cerebral protection and possible mechanism of fasudil for hypoxic-ischemic cerebral damage (HIBD) in neonatal rats. Methods The HBID model was established, then the mice were randomly divided into different groups. The expressions ofα-SMA and ROCK-2 were detected in the newborn rats with ischemia. Results Compared with the model group, expressions of α-SMA, ROCK-2 decreased in each treatment group with significant differences (P < 0.05 or P < 0.01). Following with the increases of administration dose and the administration time, expressions of α-SMA, ROCK-2 decreased gradually with significant differences (P<0.05 or P<0.01). Conclusion Fasudil can reduce the expressions of α-SMA, ROCK-2 in the newborn mice with hypoxic-ischemic brain damage to attenuate the brain tissue hypoxic-ischemic injury. The protective effect on brain is significant by giving high-dose fasudil in the early neonatal rat HIBD (0 h).