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.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative 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:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Optical tweezers are a means to manipulate objects with light. Optical tweezers can obtain a nanometer space, piconewton force, and a millisecond resolution; thus, they are excellently suited for studying biological processes from the single-cell to the single-molecule level. Optical tweezers can screen and manipulate tumor cells, study single molecule, and monitor cancer treatments. Thus, optical tweezers will promote the progress of cancer research and treatments.