ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

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.

Qingfeitang， specialized in resolving phlegm to stop cough and producing fluid to moisten dryness， is a classic prescription inherited and developed by physicians of successive generations and has been included in the Catalogue of Ancient Classic Prescriptions （First Batch） published by the National Administration of Traditional Chinese Medicine （TCM） in 2018. Relevant ancient books data and modern literature were collected by bibliometrics to analyze the historic origin， formula composition， herb origin， preparation methods， processing methods， clinical effect， and indications of Qingfeitang. The key information of Qingfeitang was summarized to provide reference for the clinical application of the decoction. In this study， a total of 43 pieces of effective data on relevant ancient literature， including 35 ancient TCM books， were collected based on a systematic collation of relevant historic and modern literature. Results showed that "Qingfeitang" was originated from the "Renshen Qingfeitang" recorded in the Taiping Holy Prescriptions for Universal Relief from the Qing dynasty. The name of "Qinfeitang" was first recorded in the Yeshi Luyanfang written by YE Dalian in the Song dynasty. We suggested the modern dosage and usage of Qingfeitang as follows： "Scutellariae Radix of 5.60 g， Platycodon grandiflora， Poria， Tangerine， Fritillaria， and Cortex Mori of 3.73 g respectively， Angelicae Sinensis Radix， Asparagi Radix， Gardeniae Fructus， Armeniacae Semen Amarum， and Ophiopogonis Radix of 2.61 g respectively， Schisandra of 1 g， and Glycyrrhizae Radix et Rhizoma of 1.12 g， and they were taken 3 times daily. The above formula is recommended to be decocted with 400 mL of water， with 3.37 g ginger and 6 g jujubae fructus， to 320 mL， and taken after a meal， three times per day". Qingfeitang has the effect of resolving phlegm to stop cough and producing fluid to moisten dryness， specialized in treating cough， asthma， rash， and other symptoms in ancient times. Modern applications are mainly focused on the respiratory system， used for treating diseases such as bronchopneumonia and cough. The above research results provide a reference basis for the later development and research of Qingfeitang.

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

Jinlingzi San is a formula frequently used in treating pain syndrome， first recorded in the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and the Safeguarding of Life as Discussed in the 'Basic Questions' written by LIU Wansu in the Jin Dynasty. Jinlingzi San is composed of 2 Chinese medicinals Toosendan Fructus and Corydalis Rhizoma with a concise composition and exact clinical efficacy， having been included in the Catalogue of Ancient Classical Formulas （Second Batch： Han Chinese Medicine）. The formula name， historic evolution， medicine origins， composition， dosage， decocting methods， and ancient and modern clinical application were sorted out and analyzed with the bibliometric method. A total of 209 pieces of information were collected from ancient books and literature. After screening， 49 pieces of effective data involving 45 ancient books were included. Results showed that the name of Jinlingzi San was first recorded in Secret Formulas of the Yang Family written by Yang Tan in the Southern Song Dynasty and developed into 3 other versions of the decoction. The Jinlingzi San included in the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and the Safeguarding of Life as Discussed in the 'Basic Questions' written by LIU Wansu invariably plays a dominant role. As for the 3 other versions， although they have the same name of Jinlingzi San， their composition and indications are different from those of the original formula， which were therefore viewed as prescriptions based on Jinlingzi San and also included in the research. The medicine origins and processing of Jinlingzi San are suggested： Toosendan Fructus is the dry mature fruit of Melia toosendan of Meliaceae， and the crude is used after cleansing without putamen. Corydalis Rhizoma is the dry tuber of Corydalis yanhusuo of Papaveraceae， which is used after impurity removal， cleaning， and drying. Depending on the conversion from the measurement system in the Jin Dynasty to modern measurement， it is suggested that Toosendan Fructus and Corydalis Rhizoma （41.3 g each） are ground into fine powder， and one dose includes 12.39 g of the powder， which should be taken with an appropriate amount of wine. If wine is not suitable for the patient， the decoction can also be taken with warm water. Jinlingzi San has the effects of soothing the liver， discharging heat， and activating blood to stop pain. As recorded in ancient books， Jinlingzi San is specialized in treating heart pain caused by reversal heat， chest and abdominal pain， hypochondriac pain， jaundice， hernia， and other diseases. Modern studies have shown that modified Jinlingzi San can be used in treating diseases involving the digestive system， the integumentary system， the gynecological system， the reproductive system， and other systems and has wide clinical application in treating epigastric pain， herpes zoster， dysmenorrhea， and other diseases. This study has made clear the key information of Jinlingzi San by textual research of ancient books and literature in the hope of providing a theoretical reference for the clinical application， set prescriptions， and new drug development.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Recent epidemiological studies have increasingly found that pregnant women who are exposed to air pollutants (for example airborne particulate matter, nitrogen oxides, ozone, and sulfur dioxide) increase the risk of various birth defects in their offspring, such as congenital heart disease, neural tube defects, cleft lip and palate, and hypospadias. Hypospadias not only impairs the sexual function of infants but also causes major social and psychological problems during their growth period, therefore, the prevention and treatment of hypospadias infant carry substantial public health importance. However, the association between prenatal exposure to air pollution and hypospadias remains controversial. The study reviews the epidemiological research progress and potential biological mechanisms of prenatal maternal exposure to air pollutants such as particulate matter, nitrogen oxides, ozone, sulfur dioxide, and the risk of hypospadias in offspring. The study also summarizes the limitations of previous research and looks forward to future research directions, to provide scientific evidence for creating a healthy living environment for pregnant women, and reducing the risk of hypospadias in offspring.