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.

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.

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.

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 To investigate the effect of mechanical stretch on the proliferation and differen-tiation of skeletal satellite cells in mice,and explore its mechanism.Methods The research was divid-ed into two parts.In the first part,all mice were not given osteogenic or adipogenic induction,and randomly divided into a control group,a mechanical stretch(MS)group,a solvent control group[Di-methyl sulfoxide(DMSO)+mechanical stretch],a Notch inhibitor(KY-02111)+mechanical stretch group and a Wnt inhibitor(FLI-06)+mechanical stretch group,with the aim to evaluate cell prolifera-tion and migration,and the effect of mechanical stretch on the Wnt and Notch signaling pathway.In the second part,all mice were randomly divided into 6 groups:a control group,an induced differentia-tion(ID)group,an induced differentiation+mechanical stretch(IDMS)group,an induced differentia-tion+DMSO+mechanical stretch(IDDMS)group,an induced differentiation+Notch inhibitor(KY-02111)+mechanical stretch(IDNMS)group,and an induced differentiation+Wnt inhibitor(FLI-06)+mechanical stretch(IDWMS)group.All groups except the control group were induced differenti-ation using osteoblastic or adipogenic medium,and the IDMS group was applied tensile stress to the cell basement membrane,with the IDDMS and IDNMS groups given DMSO and KY-02111 or FLI-06 with a final concentration of 5 μM into the culture medium,respectively.On the 7th and 14th days af-ter culture,cell proliferation was detected using CCK-8,while on the 14th day after culture,cell mi-gration was observed using the streak method.Alkaline phosphatase and oil red staining were per-formed on all cells.Moreover,the mRNA expression of osteogenic[alkaline phosphatase(ALP)and Runt-related transcription factor(Runx)-2]and adipogenic[fatty acid-binding protein(FABP)4 and li-poprteinlipase(LPL)]differentiation marker genes were quantitatively detected by using the real-time PCR.Meanwhile,while the expression of c-Myc and Cyclin B(CCNB)1 proteins was measured using Western blotting.Results Cell proliferation increased significantly in MS group compared with the con-trol group(P<0.01),while that of IDMMS and IDNMS groups decreased significantly compared with MS group.As to cell migration,MS group was significantly better than the control group(P<0.01),while there was a significant decrease in both IDMMS and IDNMS groups compared with MS group(P<0.01).According to ALP and oil red staining,a significant increase in ALP activity and lipid droplet secretion was observed in skeletal muscle satellite cells of ID groups compared with the control group,with the increase in IDMMS and IDNMS groups significantly greater than MS group.More-over,the results of real-time PCR showed that the expression of ALP and Runx-2mRNA in the osteo-genic induction group and the FABP4 and LPL mRNA in the adipogenic induction group increased sig-nificantly compared with the control group(P<0.05),with a significant decrease in the above measure-ments of IDMS group compared with ID group,but a significant increase in IDMMS and IDNMS groups compared with IDMS group(P<0.01).Meanwhile,according to Western blotting,the expres-sion of c-Myc and CCNB1proteins increased significantly in the skeletal muscle satellite cells of MS group compared with the control group(P<0.01),while that of IDMMS and IDNMS groups decreased significantly compared with MS group(P<0.01).Conclusion Mechanical stretch can promote the prolif-eration and migration of skeletal satellite cells in mice,but inhibit osteogenic and adipogenic differenti-ation.Its mechanism is related to the activation of Wnt and Notch signal pathways.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To investigate the effect of ultra-early enteral nutrition (UEEN) support on the prognosis of young and middle-aged postoperative patients with cerebral hemorrhage.Methods:The clinical data of young and middle-aged patients (aged 18-59 years) admitted to Tianjin Fifth Central Hospital from January 2020 to June 2023 after surgery for intracerebral hemorrhage were retrospectively analyzed, and the general data, nutritional indexes, gastrointestinal complications, neurological function recovery and long-term prognosis of the patients were recorded. According to the time of initiation of enteral nutrition (EN) support, patients were divided into UEEN group (EN implementation within 12 hour after surgery) and early enteral nutrition (EEN) group (EN implementation within 24 to 48 hour after surgery). The differences of the above indexes between the two groups were analyzed and compared.Results:A total of 64 young and middle-aged postoperative patients with cerebral hemorrhage were enrolled, including 32 cases in the UEEN group and 32 cases in the EEN group. There were no significant differences in gender, age, proportion of hypertension and diabetes, Glasgow coma score (GCS) on admission and surgical methods between the two groups. In terms of nutritional indexes, serum total protein, albumin and hemoglobin levels of patients in both groups on day 7 after admission were lower than those on day 1, and higher than those on day 3, and the above indexes levels in UEEN group were significantly higher than those in EEN group on day 7 [total protein (g/L): 63.05±5.79 vs. 59.02±6.63, albumin (g/L): 40.40±5.26 vs. 37.66±4.63, hemoglobin (g/L): 133.33±12.58 vs. 123.80±22.12, all P < 0.05]. In terms of gastrointestinal complications, the incidence of stress ulcer in the UEEN group within 14 days after admission was significantly lower than that in the EEN group [12.5% (4/32) vs. 31.3% (10/32), P < 0.05], but there was no statistically significant difference in feeding intolerance symptoms between the two groups. In terms of neurological recovery and long-term prognosis, GCS scores and Barthel index scores of 14 days after admission were higher than those of 1 day after admission, but there was no statistical significance between the two groups. Six months after surgery, Glasgow outcome scale (GOS) and Barthel index score of the UEEN group were significantly higher than those of the EEN group (GOS score: 3.81±1.06 vs. 3.18±1.07, Barthel index score: 60.78±7.24 vs. 54.52±5.13, both P < 0.05). Conclusion:UEEN support can improve the nutritional level of young and middle-aged postoperative patients with cerebral hemorrhage, reduce the occurrence of postoperative gastrointestinal complications, promote the recovery of neurological function, and improve the long-term prognosis.