Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

When prostate cancer （PCa） progresses to the metastatic castration-resistant stage， significant challenges arise in clinical treatment. Microtubulin inhibitors have become first-line drugs for the treatment of metastatic castration-resistant PCa due to their unique mechanism of action. Among them， taxanes （e.g. docetaxel and cabazitaxel） remain standard care with proven survival benefits， while other microtubule inhibitors （e.g. vincristine， colchicine） show limited clinical utility due to toxicity. Currently， the clinical approach primarily employs docetaxel-based triple therapy and combined with immune checkpoint inhibitors to improve the prognosis of PCa patients， reverse the immunosuppressive state of the tumor microenvironment， and enhance therapeutic efficacy. Despite the remarkable clinical efficacy of microtubule inhibitors in the treatment of PCa， the emergence of drug resistance has limited their long-term application. To address this issue， researchers have explored new solutions， including the development of novel microtubule inhibitors in combination with ATP-binding cassette subfamily B member 1 inhibitors， the concurrent use of fatty acid synthase inhibitors with microtubule inhibitors， and the development of degraders based on proteolysis-targeting chimeras technology. Future research should focus on target discovery， drug formulation optimization， and personalized approaches to overcome current therapeutic limitations.

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

With the advent of an aging society,Alzheimer's disease(AD)has gradually become a major ailment affecting the elderly.AD is a neurodegenerative disorder associated with cognitive impairments.In AD patients,brain network connections are disrupted,and their topological properties are also affected,leading to the disintegration of anatomical and functional connections.Anatomical connections can be tracked and evaluated using structural magnetic imaging(MRI)and diffusion tensor imaging(DTI),while functional connections are detected through functional MRI to assess their connectivity status.This review incorporates the findings of previous scholars and summarizes the current research of AD.It mainly discusses the imaging characteristics of large-scale brain network changes in AD patients,so as to provide researchers with scientific and objective imaging markers for AD prediction and early diagnosis,as well as future research.

Objective To compare the anesthetic effect and safety of remimazolam and propofol on patients underwent video-assisted thoracoscopic surgery for lung cancer.Methods Clinical data of patients with lung cancer underwent video-assisted thoracoscopic surgery were retrospectively collected.Remimazolam group was anesthetized by remimazolam,and propofol group was anesthetized by propofol.The changes in mean arterial pressure(MAP)and heart rate(HR)were compared between the two groups of patients before anesthesia induction(T0),after 5 min of tracheal intubation(T1),after 1 h of surgery(T2),during thorax closure(T3)and at 5 min after extubation(T4).The sedation onset time,recovery time and extubation time in the two groups were recorded.Stress response indicators[adrenocorticotropic hormone(ACTH),cortisol(Cor)]were compared at T0 and T4.Ramsay sedation score(RSS)was used to assess the sedation degree at T4.Visual analogue score(VAS)was applied to evaluate the pain degree at 2,12 and 24 h after surgery,and the perioperative anaesthesia-related adverse events were observed.Results There were 58 cases in remimazolam group and 64 cases in propofol group.The MAP values at T1 in remimazolam group and propofol group were(85.03±4.37)and(78.24±4.48)mmHg;at T2 were(80.39±3.95)and(75.49±4.11)mmHg;at T3 were(84.43±4.02)and(79.59±3.97)mmHg;the HR values at T2 were(76.44±5.75)and(72.39±6.03)beat·min-1,the difference were all significant(all P＜0.05).The sedation onset times in remimazolam group and propofol group were(62.45±6.27)and(72.33±7.19)s;the recovery times were(7.22±1.23)and(8.24±1.48)min;the extubation times were(8.34±1.50)and(10.09±1.83)min;the RSS scores at T4 were(2.03±0.39)and(1.88±0.35)points,the difference were all significant(all P＜0.05).The total incidence rates of anesthesia-related adverse events in remimazolam group and propofol group were 6.90％and 21.88％,respectively(P＜0.05).Conclusion Both remimazolam and propofol can play a good sedative effect during lung cancer video-assisted thoracoscopic surgery anesthesia.Remimazolam anesthesia has more stable intraoperative hemodynamics,faster onset and elimination,and higher safety.

Objective To investigate the effect of dapagliflozin-mediated miR-98-5p on high glucose-induced damage in human renal tubular epithelial cells.Methods Blood samples from patients with diabetic nephropathy(DN)and healthy individuals were collected.The expression of serum miR-98-5p was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR),and kidney injury-related indicators were measured using a biochemical immunoassay analyzer.HK-2 cells were cultured in vitro and randomly divided into control group(5 mmol·L-1 glucose),HG group(30 mmol·L-1 glucose),experimental-L group(30 mmol·L-1 glucose+20 μmol·L-1 dapagliflozin),experimental-H group(30 mmol·L-1 glucose+40 μmol·L-1 dapagliflozin),anti-miR-NC group(transfected with anti-miR-NC+30 mmol·L-1 glucose+40 μmol·L-1 dapagliflozin),and anti-miR-98-5p group(transfected with anti-miR-98-5p+30 mmol·L-1 glucose+40 μmol·L-1 dapagliflozin).Cell viability was evaluated using the cell counting kit 8(CCK-8)assay 24 hours after drug treatment;miR-98-5p expression in cells was detected by RT-qPCR;cell apoptosis rate was measured by flow cytometry,apoptosis-related protein expression was detected by Western blot;and inflammatory cytokine expression was measured by enzyme-linked immunosorbent assay.Results The expression levels of miR-98-5p in the serum of DN patients and healthy individuals were 1.00±0.25 and 0.39±0.05,respectively,showing a significant difference between the two groups(P＜0.05).The expression levels of miR-98-5p in the control group,HG group,experimental-H group,anti-miR-NC group,and anti-miR-98-5p group were 1.00±0.09,0.31±0.04,0.72±0.06,0.75±0.07 and 0.22±0.03;the cell survival rates were(100.00±3.36)％,(51.63±5.89)％,(79.46±9.90)％,(82.88±5.71)％and(59.69±7.43)％;apoptosis rates were(3.52±0.20)％,(35.80±3.67)％,(16.43±1.57)％,(15.71±1.42)％and(29.37±2.18)％;tumor necrosis factor-α(TNF-α)levels were(22.46±1.67),(68.37±6.05),(34.45±2.47),(35.11±2.84)and(60.46±3.56)pg·mL-1,respectively.The differences among these indicators were all statistically significant when comparing the HG group to the control group,the experimental-H group to the HG group,and the anti-miR-98-5p group to the anti-miR-NC group(all P＜0.05).Conclusion Dapagliflozin can alleviate high glucose-induced HK-2 cell damage by upregulating the expression of miR-98-5p,inhibiting inflammation,and reducing cell apoptosis.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Objective:To analyze the acute poison epidemic and provide evidence for developing prevention and control strategies for acute poisoning.Methods:A retrospective analysis was conducted on acute poisoning cases collected from 2016 to 2022 in a health emergency information platform for acute poisoning accidents. The cases were grouped according to the distribution of poisoning occurrence time, geographic distribution, demographic distribution, types of toxicants, poisoning causes, and outcomes. Data were organized and analyzed using Excel 2016 and R 4.2.3.Results:A total of 95 754 acute poisoning cases were included in this study. The primary toxicants were pesticides, drugs, and industrial/household chemicals, accounting for 30.4%, 22.4%, and 20.4% of the total cases, respectively. Acute poisoning occurred throughout the year, with the highest frequency from June to August, accounting for 31.9%. The seasonal distribution varied among different types of toxicants. Except for plant poisoning, which showed a bimodal distribution, the other poisonings showed an unimodal distribution. There was a strong seasonality in fungal poisoning, which peaked in July. There was an obvious seasonality in animal poisoning, with a peak in August. The proportion of biological poisonings in the southwest region was higher than in other regions, including plants, animals, and fungi. There were more females than males, and their education level was mainly junior high school and below (35.2%). The main occupation was farmers (34.2%), and the main causes of poisoning were accidents and suicides. The case fatality rate of all poisoning cases was 1.24%. Pesticide poisoning was the most common type, and chlorfenapyr (11.68%), Diquat (7.23%), and paraquat (7.05%) ranked as the top three toxicants.Conclusions:The occurrence of acute poisoning has an obvious seasonal trend, and the toxicant spectrum of different regions and populations is different. A comprehensive poisoning surveillance system can provide a better understanding of the occurrence of poisonings, and facilitate the formulation of more scientifically precise poisoning prevention and control strategies.