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.

Human exhaled breath has great application prospects,e.g.,monitoring pharmacokinetics,disease diagnosis,due to its advantages such as non-invasive and high-frequency sampling.Breath samples can be collected from the oral and nasal cavity.However,the oral and nasal environment affect the chemical composition of breath sample.Therefore,the investigation on the chemical composition of mouth-exhaled breath and nose-exhaled breath is crucial for selection of appropriate sampling strategy for individual studies.In this work,secondary electrospray ionization-high resolution mass spectrometry(SESI-HRMS)was applied to analysis of respiratory metabolomics in real time.A quantitative analysis approach was established for 9 kinds of volatile organic compounds(VOCs)e.g.2-butanone,2-pentanone,ethyl acetate,methyl methacrylate,toluene,styrene,mesitylene,isoprene and limonene.The limit of detection was 2.3?240.8 ng/m3.The intra-day(n=6)and inter-day(n=18)relative standard deviations were 0.6%?4.6%and 4.3%?12.2%,respectively.Nine healthy subjects were recruited to investigate the chemical composition of mouth-exhaled and nose-exhaled breath.The results showed the good performance in quantitative analysis of 9 VOCs in breath air.It was found that the number of unique component(m/z)detected in mouth-exhaled breath(167)was 2.2 times greater than that detected in nose-exhaled breath(76),which might result from the complex environment in oral cavity.The signal intensity of commun component(163)was significantly different between mouth-exhaled breath and nose-exhaled breath.Additionally,the elemental composition analysis showed that the proportion of polar compounds detected in nose-exhaled breath was higher than that in mouth-exhaled breath.This study demonstrated that there was significant differences in the chemical composition between mouth-exhaled and nose-exhaled breath,which provided a theoretical basis for selection of exhalation mode.

Sesquiterpenoids are widely found in nature, while nitrobenzoyl sesquiterpenoids are relatively rare. Twelve natural nitrobenzoyl sesquiterpenoids were all derived from marine Aspergillus fungi, which are typical natural products with marine characteristics. These natural products exhibit good antitumor, antiviral, and inhibition of osteoclast differentiation activity, especially in the treatment of osteoclast-related diseases, showing good medicinal development value. This article reviews the natural product sources, chemical structure, chemical synthesis, biosynthesis, bioactivity, and pharmacological mechanisms of nitrobenzoyl sesquiterpenoids and predicts and discusses their absorption, distribution, metabolism, excretion, toxicity (ADME/T), and drug-likeness, providing a comprehensive understanding of the natural products of nitrobenzoyl sesquiterpenoids from marine sources and their potential for pharmaceutical development.

Objective To explore the correlation between the immune related adverse(irAEs)reactions in patients treated with pembrolizumab and traditional Chinese Medicine(TCM)constitution.Methods A total of 110 patients diagnosed with non-small cell lung cancer for the first time were selected.When receiving pembrolizumab immunotherapy for the first time,a general information questionnaire,a TCM constitution classification and judgment scale,an immune related adverse reaction follow-up record book,and a patient's self-perception diary were used to investigate and analyze the TCM syndrome and adverse reactions of the patients.Results Among non-small cell lung cancer patients,there were more than four TCM constitutions,with 48 cases(43.64%)having a calm constitution,20 cases(18.18%)having a biased constitution,30 cases(27.27%)having a yang deficiency constitution,and 12 cases(10.91%)having a yin deficiency constitution.Qi deficiency and Yang deficiency were more prone to fatigue,while Yang deficiency was more prone to rash;Qi deficiency and Yin deficiency were more prone to itching;Yang deficiency was more prone to diarrhea;Non-small cell lung cancer patients with mild constitution were less prone to immune related adverse reactions.Conclusion TCM constitution is related to irAEs,which could predict the occurrence of immune related adverse reactions from the perspective of TCM constitution and intervene in adverse reactions early.

Human genetic resources are an indispensable part of national natural science and technology resources,as well as an important strategic resource for safeguarding national security,public health,and social public interests.To promote the effective protection and rational utilization of human genetic resources,as well as improve and optimize the local human genetic resources management system in China,this paper summarized the current situation of administrative approval and supervision of national human genetic resources from 2004 to 2021 by sorting out the national human genetic resources management policies and regulations.Furthermore,the current situation and progress of local human genetic resources management in China were understood from three aspects,including development planning and programs of human genetic resources,administrative licensing and penalties,and the construction of management expert committees.The main problems of local human genetic resources management in China were discussed and analyzed,such as unclear supervision,difficulty in supervision and inspection,and capacity for services.Based on the causes of the problems and the local management work,specific countermeasures and suggestions were put forward from the perspective of clarifying the regulatory policies and procedures for human genetic resources,improving the supervision and inspection mechanisms,and improving the management and service capabilities.

The chimeric antigen receptor T cell(CAR-T)therapy products approved for market and under development mainly targets the B-cell receptor-related protein CD19.This paper relies on the pharmacovigilance database during clinical trials of the Center for Drug Evaluation National Medical Products Administration.We retrospectively analyzed the 113 individual case safety expedited reports of suspected unexpected serious adverse reactions of CAR-T cell therapy products containing B-cell receptor-rolated protein CD19 from domestic clinical trials received from January 1,2021 to May 20,2024.Strengthen risk management according to product characteristics.It is expected that through this paper,the sponsors can improve the pharmacovigilance regime and system,timely report according to the requirements,strengthen the risk communication with the regulatory authorities,form a joint force with the regulatory authorities,and jointly do a good job in risk management during clinical trials.

In recent years,chimeric antigen receptor T cell(CAR-T)therapeutic products have shown good efficacy in the treatment of blood tumors,and breakthroughs have also been made in the treatment of solid tumors and autoimmune diseases.In order to further understand the clinical research and development progress of CAR-T products,this paper mainly uses the drug clinical trial registration and information publication platform of the Center for Drug Evaluation National Medical Products Administration as the information source,and focuses on the statistical analysis of the clinical trial progress of domestic CAR-T cell therapy products containing the targeted B-cell receptor-related protein CD19.It is hoped to further improve the quality and efficiency of clinical research and development of CAR-T cell therapy products,strengthen the sponsor's awareness of main responsibility,and timely update trial information to protect the rights and interests of subjects during clinical trials.

Pancreatic cancer (PC) is a highly fatal disease which originated from pancreatic epithelial and acinar cells, and the survival rate of pancreatic cancer patients is only about 12%. Approximately 95% of pancreatic cancer presents as ductal adenocarcinoma (PDAC). Pancreatic cancer is characterized by high aggressiveness, rapid progression and progression, and high resistance to treatment. Common somatic mutated genes in the early stage of pancreatic cancer include KRAS, CDKN2A, TP53, and SMAD4. Most pancreatic cancer patients are affected by environmental risk factors such as age, sex and diet. Malignant pancreatic cancer is associated with non-invasive, preneoplastic lesions that are thoughted to be precursors, such as pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN) and mucinous cystadenoma (MCN). In recent years, people have gradually improved the therapy and diagnosis of pancreatic cancer, and the contribution of imaging technology, which enhancing the usage of minimally invasive pancreatectomy that typically includes pancreaticoduodenectomy and distal pancreatectomy. However, combined administration of the chemotherapeutic gemcitabine and erlotinib is still considered a potential first-line treatment for advanced pancreatic cancer, but the development of chemoresistance often leads to poor therapeutic outcomes. Based on the current research progress for pancreatic cancer, its treatment currently remains one of the most important challenges in the medical field. Although some new treatment options have been provided, there were minor clinical success achieved and therefore new safe and effective therapies of pancreatic cancer are still an urgent need for patients. Among these new therapies for pancreatic cancer, short peptide-based treatment protocols have attracted great attention. Peptide is a compound formed by linking α-amino acids together in peptide chains. It is also an intermediate product of proteolysis. The short peptide-based therapy has many advantages such as precise targeting, easy preparation and low toxicity. Short peptides usually act as tumor suppressors by targeting and recognizing tumor-specific expressed proteins. Currently, there is an increased interest in peptides in pharmaceutical and development research, and approximate 140 peptide therapeutics are currently being evaluated in clinical trials. These peptides provide excellent prospects for targeted drug delivery because of their high selectivity, specificity and simplicity of modification. Peptides have high bioactivity and excellent biodegradability. Clinically, short peptides are increasingly used as combination drugs with chemotherapy for tumor treatment. Peptides can induce cancer cell death by numerous mechanisms and peptides have emerged as a promising drug for the treatment of pancreatic cancer. Here we mainly review the roles of peptides on Wnt/β-catenin, NF-κB, autophagy, and the use of peptides as tracer in pancreatic cancer. We also analyzed the benefits and disadvantages existing in the development process of short peptides, which provide the feasibility of targeted short peptides to become new therapeutic approaches for cancer therapy.