OBJECTIVE To observe the effects of Modified shaoyao gancao decoction on intestinal transit function， intestinal flora and the contents of metabolites [γ aminobutyric acid （GABA） and 5-hydroxytryptamine （5-HT）] in slow transit constipation （STC） rats. METHODS SD rats were randomly divided into blank group （10 rats） and modeling group （30 rats）， with half male and half female. The STC model was established by intragastric administration of Compound diphenoxylate tablets in the modeling group. The successfully modeled rats were randomly divided into model group， Modified shaoyao gancao decoction group [56 g/（kg·d）， calculated by crude drug] and positive control group [lactulose 2.09 g/（kg·d）]， with 10 rats in each group. Each administration group was given relevant medicine intragastrically， the blank group and model group received an equivalent volume of normal saline， once a day， for 14 consecutive days. During the experiment， the general situation of rats was observed in each group. After the last medication， the body weight was measured， and the Bristol score was used to evaluate the fecal characteristics. The fecal moisture content， intestinal propulsion rate， and the contents of GABA and 5-HT in intestinal content were detected； the diversity of intestinal flora in intestinal contents was investigated， and the correlation between the contents of GABA， 5-HT and relative abundance of microbiota was analyzed. RESULTS Compared with the model group， general conditions such as small body shape， sparse and rough fur， and slow movement were all improved in Modified shaoyao gancao decoction body weight， Bristol score， fecal moisture content，intestinal propulsion rate， 5-HT content， Chao1 index and Shannon index were increased significantly， while GABA content and Simpson index were decreased significantly （P＜0.05）. The intestinal flora of rats in the Modified shaoyao gancao decoction group could be classified as the same as the blank group， but was far from the model group； the relative abundances of Desulfobacterota， Firmicutes and Bacteroidota in this group showed a tendency of pull back， but the differences were not statistically significant compared to model group （P＞0.05）. Desulfobacterota was an intergroup differential factor （P＜0.05）. The content of GABA was negatively correlated with the relative abundance of Bacteroidota， Cyanobacteria， Patescibacteria and Actinobacteriota （P＜0.05）. The content of 5-HT was positively correlated with the relative abundance of Campilobacterota （P＜0.05）. CONCLUSIONS Modified shaoyao gancao decoction can improve the fecal properties and intestinal motility of STC rats. Its mechanism may be related to improving intestinal flora and then affecting the contents of GABA and 5-HT in intestinal contents. In addition， the contents of GABA and 5-HT may be significantly correlated with the relative abundance of specific bacterial phyla such as Bacteroidota and Campilobacterota.

OBJECTIVE To observe the effects of Modified shaoyao gancao decoction on intestinal transit function， intestinal flora and the contents of metabolites [γ aminobutyric acid （GABA） and 5-hydroxytryptamine （5-HT）] in slow transit constipation （STC） rats. METHODS SD rats were randomly divided into blank group （10 rats） and modeling group （30 rats）， with half male and half female. The STC model was established by intragastric administration of Compound diphenoxylate tablets in the modeling group. The successfully modeled rats were randomly divided into model group， Modified shaoyao gancao decoction group [56 g/（kg·d）， calculated by crude drug] and positive control group [lactulose 2.09 g/（kg·d）]， with 10 rats in each group. Each administration group was given relevant medicine intragastrically， the blank group and model group received an equivalent volume of normal saline， once a day， for 14 consecutive days. During the experiment， the general situation of rats was observed in each group. After the last medication， the body weight was measured， and the Bristol score was used to evaluate the fecal characteristics. The fecal moisture content， intestinal propulsion rate， and the contents of GABA and 5-HT in intestinal content were detected； the diversity of intestinal flora in intestinal contents was investigated， and the correlation between the contents of GABA， 5-HT and relative abundance of microbiota was analyzed. RESULTS Compared with the model group， general conditions such as small body shape， sparse and rough fur， and slow movement were all improved in Modified shaoyao gancao decoction body weight， Bristol score， fecal moisture content，intestinal propulsion rate， 5-HT content， Chao1 index and Shannon index were increased significantly， while GABA content and Simpson index were decreased significantly （P＜0.05）. The intestinal flora of rats in the Modified shaoyao gancao decoction group could be classified as the same as the blank group， but was far from the model group； the relative abundances of Desulfobacterota， Firmicutes and Bacteroidota in this group showed a tendency of pull back， but the differences were not statistically significant compared to model group （P＞0.05）. Desulfobacterota was an intergroup differential factor （P＜0.05）. The content of GABA was negatively correlated with the relative abundance of Bacteroidota， Cyanobacteria， Patescibacteria and Actinobacteriota （P＜0.05）. The content of 5-HT was positively correlated with the relative abundance of Campilobacterota （P＜0.05）. CONCLUSIONS Modified shaoyao gancao decoction can improve the fecal properties and intestinal motility of STC rats. Its mechanism may be related to improving intestinal flora and then affecting the contents of GABA and 5-HT in intestinal contents. In addition， the contents of GABA and 5-HT may be significantly correlated with the relative abundance of specific bacterial phyla such as Bacteroidota and Campilobacterota.

OBJECTIVE To explore the mechanism of Shaoyao gancao decoction in improving intestinal motility in rats with slow transit constipation （STC） by regulating acid-sensitive ion channel 3 （ASIC3）/extracellular signal-regulated kinase （ERK） signaling pathway. METHODS SD rats were used to construct an STC model by gavage with compound diphenoxylate. The successfully modeled rats were randomly divided into model group， Shaoyao gancao decoction group （1.5 g/mL）， lactulose group （208.4 mg/mL， positive control）， and combined inhibition group （Shaoyao gancao decoction 1.5 g/mL+amiloride hydrochloride 20 μg/kg）， with 12 rats in each group. Additionally， 12 healthy rats were selected as the blank group. They were given relevant medicine once a day and continuously intervened for 14 days. After intervention， the intestinal propulsion function and visceral sensitivity of the model rats were detected. The expression of ASIC3 in the colon tissue of rats was observed by immunohistochemical staining. mRNA expressions of ASIC3， ERK1 and ERK2 as well as protein expressions of ASIC3， ERK1/2 and phosphorylated ERK1/2 （p-ERK1/2） in colon tissue of rats were detected； the ultrastructural changes of the enteric nervous system （ENS） -interstitial cell of Cajal （ICC）-smooth muscle cell （SMC） network in the rat colon were observed under electron microscopy. RESULTS Compared with the model group， the intestinal propulsion rate of the Shaoyao gancao decoction group was significantly increased， while the visceral pain threshold was significantly decreased. The proportion of the positive area of ASIC3 in the colonic tissue was significantly increased. The relative mRNA expression levels of ERK1， ERK2， and ASIC3， as well as the relative protein expression levels of p-ERK1/2 and ASIC3， and the p-ERK1/2 to ERK1/2 in the colonic tissue， were all significantly increased （P＜0.05 or P＜0.01）. Additionally， there was marked repair of the morphological structure of ICC and SMC， with closer gap junctions observed. Compared with the Shaoyao gancao decoction group， the combined inhibition group exhibited a diminished improvement in intestinal motility of rats， with statistically significant differences in the levels of some indicators （P＜0.05 or P＜0.01）； the repairing of the morphological structure of ICC and SMC was notably attenuated. CONCLUSIONS Shaoyao gancao decoction can effectively improve the intestinal transmission function and promote intestinal repair in STC rats， and its mechanism may be related to regulating the balance of the ENS-ICC-SMC network mediated by the ASIC3/ERK signaling pathway， thus promoting intestinal motility and reducing visceral sensitivity.

As one of the typical bioorthogonal chemistry reactions, click chemistry joins molecules similar to “Lego”. Bioorthogonal click chemistry is used to modify cancer cells, design antitumor drugs, delivery drugs, manipulate immune cells, and help preclinical evaluation. Click chemistry provides a promising approach for discovering molecules and targeting cancer in cancer research.

Objective In this study,we analyzed the transcriptome sequences of Kupffer cells exposed to simulated microgravity for 3 d and conducted biological experiments to determine how microgravity initiates apoptosis in Kupffer cells. Methods Rotary cell culture system was used to construct a simulated microgravity model.GO and KEGG analyses were conducted using the DAVID database.GSEA was performed using the R language.The STRING database was used to conduct PPI analysis.qPCR was used to measure the IL1B,TNFA,CASP3,CASP9,and BCL2L11 mRNA expressions.Western Blotting was performed to detect the level of proteins CASP3 and CASP 9.Flow cytometry was used to detect apoptosis and mitochondrial membrane cells.Transmission electron microscopy was used to detect changes in the ultrastructure of Kupffer cells. Results Transcriptome Sequencing indicated that simulated microgravity affected apoptosis and the inflammatory state of Kupffer cells.Simulated microgravity improved the CASP3,CASP9,and BCL2L11 expressions in Kupffer cells.Annexin-V/PI and JC-1 assays showed that simulated microgravity promoted apoptosis in Kupffer cells.Simulated microgravity causes M1 polarization in Kupffer cells. Conclusion Our study found that simulated microgravity facilitated the apoptosis of Kupffer cells through the mitochondrial pathway and activated Kupffer cells into M1 polarization,which can secrete TNFA to promote apoptosis.

Objective:To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis (DIHS-HLH).Methods:This was a retrospective case study. Clinical characteristics, laboratory results, treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children′s hospital between January 2020 and December 2022 were summarized. Kaplan-Meier survival analysis was used to calculate the overall survival rate.Results:Among all 9 cases, there were 6 males and 3 females, with the age ranged from 0.8 to 3.1 years. All patients had fever, rash, hepatomegaly and multiple lymph node enlargement. Other manifestations included splenomegaly (4 cases), pulmonary imaging abnormalities (6 cases), central nervous system symptoms (3 cases), and watery diarrhea (3 cases). Most patients showed high levels of soluble-CD25 (8 cases), hepatic dysfunction (7 cases) and hyperferritinemia (7 cases). Other laboratory abnormalities included hemophagocytosis in bone marrow (5 cases), hypofibrinogenemia (3 cases) and hypertriglyceridemia (2 cases). Ascending levels of interleukin (IL) 5, IL-8 and interferon-γ (IFN-γ) were detected in more than 6 patients. All patients received high dose intravenous immunoglobulin, corticosteroid and ruxolitinib, among which 4 patients were also treated with high dose methylprednisolone, 2 patients with etoposide and 2 patients with cyclosporin A. After following up for 0.2-38.6 months, 7 patients survived, and the 1-year overall survival rate was (78±14)%. Two patients who had no response to high dose immunoglobulin, methylprednisolone 2 mg/(kg·d) and ruxolitinib died. Watery diarrhea, increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive.Conclusions:For children with fever, rash and a suspicious medication history, when complicated with hepatomegaly, impaired liver function and high levels of IL-5 and IL-8, DIHS-HLH should be considered. Once diagnosed with DIHS-HLH, suspicious drugs should be stopped immediately, and high dose intravenous immunoglobulin, corticosteroid and ruxolitinib could be used to control disease.

[Objective]To evaluate the efficacy and safety of total oral regimens containing pomalidomide as a second-line treatment strategy in multiple myeloma.[Methods]A total of 22 patients with multiple myeloma placed on total oral regimens containing pomalidomide as a second-line therapy from March 2020 to December 2023 were retrospectively analyzed to evaluate the treatment response,survival and safety.[Results]The median age of the 22 patients was 71.5 years old. The total oral treatment regimens containing pomalidomide included IPD (7 cases),PCD (11 cases),XPD (2 cases),and PD (2 cases). The median number of treatment cycles was 14. Among the 13 patients with prior lenalidomide exposure,ORR was 53.85％,of which 23.08％ was ≥VGPR. In 9 patients without prior lenalidomide exposure,the ORR was 77.78％,and of which 55.56％ was ≥VGPR. There was no significant difference in ORR between these two groups (P=0.38). In 12 patients with high genetic risk,the ORR was 50％,and ≥VGPR was 16.67％. The median follow-up time was 10.6 months. Disease progressed in 10 patients and death occurred in 6 patients of them. The median progression free survival (PFS) was not reached (not reached and 10.6 months in non-lenalidomide-exposure patients or lenalidomide-exposure patients,respectively).The high grade treatment-related adverse events (AEs)(≥3 ) were reported in 18.18％ patients,including granulocytopenia,thrombocytopenia,and pulmonary infection. There was no treatment-related death.[Conclusion]Total oral regimens containing pomalidomide as a second-line therapy is generally effective and safe for multiple myeloma patients.

Cancer phenotypic plasticity includes dedifferentiation, blocked differentiation and trans- differentiation, and differentiation therapy targeting tumor cell plasticity is becoming a new therapeutic model for human cancers. The application of inducing differentiation, initiating differentiation and regulating differentiation in tumor differentiation therapy will promote the directed differentiation of tumor cells into mature cells and the remodeling of phenotypes, thus to achieve the purpose of cancer treatment.

Cytotoxic agents, molecular targeted agents and immune checkpoint inhibitors consist of the fundamental model of cancer systematic treatments. Anti-tumor drugs with new mechanisms of action, including kinase inhibitors, therapeutic antibodies, nucleic acid blocks, therapeutic vaccines, gene-edited immune cells, living microrobots and digital drugs, will change this existing model. Drugs targrting nerves, polysaccharides, lipids and microflora may gradually enter clinical applications.

Objective To analyze the risk factors of nosocomial infection in inpatients with mental disorders.Methods A total of 12 861 inpatients at the Second Affiliated Hospital of Xinxiang Medical University from January to December 2023 were selected as the research subjects.Clinical data of patients were collected,and related risk factors for nosocomial infection were analyzed through univariate and multivariate logistic regression analyses.Results Of 12 861 inpatients with mental disorders,315(2.45％)had nosocomial infection.The main infection site was the respiratory tract,accounting for 87.31％.Univariate analysis showed that gender,age,length of hospital stay,classification of mental illness,self-awareness,type of drugs,patient management style,and comorbid underlying diseases were related to nosocomial infection(P＜0.05);hospitalization quarter,modified electroconvulsive therapy,protective constraint,and invasive procedure were not related to nosocomial infection(P＞0.05).Multivariate logistic regression analysis showed that length of hospital stay＞30 days,severe mental illness,closed mana-gement,age ≥ 60 years,male,and type of drugs＞2 were independent risk factors for nosocomial infection in psychiatric inpa-tients(P＜0.05).Conclusion Nosocomial infection is common in hospitalized patients with mental disorders.The length of hospital stay＞30 days,severe mental illness,closed management,age ≥ 60 years,male,and type of drugs＞2 are independent risk factors for nosocomial infection in psychiatric inpatients,and special attention should be paid to such patients.Targeted monitoring should be carried out to identify high-risk infection cases timely,and targeted prevention and control measures should be formulated to reduce the incidence of nosocomial infection in hospitalized patients with mental disorders.