ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:The relationship of peripheral blood B cell count with clinical features,laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed.Results:Patients were divided into low B-cell count group(B cell＜0.1 × 109/L,n=34)and high B-cell count group(B cell≥0.1 × 109/L,n=33)according to the median B cell count values.Compared with the high B cell count group,the low B cell count group had a higher proportion of patients with Lugano stage Ⅲ-Ⅳ,elevated LDH,elevated β2-MG and IPI score 3-5 and increased CRP(P=0.033,0.000,0.023,0.001,0.033).The peripheral CD3+and CD4+cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group(P=0.010,0.017).After initial treatment,overall response rate(ORR)and complete remission(CR)rate in high B cell count group were significantly higher than those in low B cell count group(P=0.032,0.013).The median follow-up time of patients was 23(2-77)months,progression-free survival(PFS)and overall survival(OS)of patients in the high B cell count group were significantly better than those in the low B cell count group(P=0.001,0.002).Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS(HR=4.108,P=0.002;HR=8.218,P=0.006).Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS(HR=3.116,P=0.037).Conclusion:Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy,which is associated with poor clinical prognosis.

Objective:To explore the treatment methods and clinical efficacy of penetrating high-voltage electric burns to thoracoabdominal wall.Methods:This study was a retrospective observational study. From March 2020 to March 2023, six male patients with penetrating high-voltage electric burns to thoracoabdominal wall who met the inclusion criteria were hospitalized at West China Hospital of Sichuan University, aged 42 to 57 years. Among them, one patient had thoracoabdominal wall defects with perforation and necrosis of the gastric wall and diaphragm, two patients had thoracoabdominal wall defects with perforation and necrosis of the gastric wall alone, and three patients had abdominal wall defects with perforation and necrosis of the small intestine. In the emergency department, aesthetic plastic and burn surgery, general surgery, and/or thoracic surgery doctors jointly formulated an emergency surgery plan for the patients. Three patients with perforation and necrosis of the gastric wall underwent subtotal gastrectomy and anastomosis. One of them, who also had diaphragmatic perforation and necrosis, underwent resection of the necrotic diaphragm and repair. The other three patients with perforation and necrosis of the small intestine underwent resection and anastomosis of the necrotic intestinal segment. After debriding the thoracoabdominal wall wounds conservatively in stage Ⅰ and repairing the abdominal wall defects with greater omentum coverage, the thoracoabdominal wall wounds were treated with vacuum sealing drainage (VSD). Seven days later, a stage Ⅱ thorough debridement of the thoracoabdominal wall wounds was performed, and bovine acellular dermal matrix was transplanted onto the surface of the greater omentum and the surrounding skin wounds without skin coverage, and the VSD treatment of the thoracoabdominal wall wounds was continued. After 7 days, the VSD treatment was stopped, and after the fresh granulation tissue well developed in the wounds, a stage Ⅲ transplantation of meshed split-thickness skin graft from the lateral femur was performed to close the thoracoabdominal wall wounds, followed by continuing VSD treatment for another 7 days. Data were recorded including the status of patients' enteral nutrition recovery and occurrence of complications such as abdominal infection after stage Ⅰ surgery, the time from starting moist dressing change to the wound being ready for skin grafting after stage Ⅱ surgery, the microbiological culture of wound exudate samples and conditions of wound surrounding areas from starting moist dressing change to wound healing after stage Ⅱ surgery, skin graft survival, and wound healing time. Follow-up was carried out to observe the occurrence of gastrointestinal symptoms, abdominal wall hernia, scars, and functional disorders, etc.Results:All six patients resumed enteral nutrition on day 2 to 4 after stage Ⅰ surgery, with no occurrence of intestinal obstruction, anastomotic leakage, or abdominal infection. The time from starting moist dressing change to the wound being ready for skin grafting after stage Ⅱ surgery was 8 (6, 12) days. During the period from starting moist dressing change to wound healing after stage Ⅱ surgery, microbiological culture of wound exudate sample showed Enterobacter cloacae in one patient and Pseudomonas aeruginosa in another patient, while the remaining four patients had negative cultures; no patient developed wound edge inflammation. All grafted skin survived, and the wound healing time was 38 (30, 46) days. During follow-up from 12 to 36 months after stage Ⅲ surgery, patients had no intractable constipation or intestinal obstruction symptoms, no obvious local tissue herniation requiring surgical treatment, no scar ulceration, and no functional disorders. Conclusions:For penetrating high-voltage electric burns to thoracoabdominal wall, a sequential three-stage surgical treatment plan under a multidisciplinary team collaboration model can effectively protect organ function and control wound infection. Long-term follow-up shows good gastrointestinal function and thoracoabdominal wall appearance. This method is highly reproducible and effective, which is suitable for clinical promotion and use.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

ObjectiveTo investigate the effects of thyme herbal tea （BLX） on the proliferation of human coronavirus OC43 （HCoV-OC43） in vitro and in vivo. MethodThe chemical composition of BLX was analyzed by UPLC-MS. The cytotoxicity of BLX in HRT-18 cells and the effect of BLX treatment on the proliferation of HCoV-OC43 in cells were analyzed. Copies of viral gene were detected by real-time PCR. The effect of BLX treatment on the life cycle of HCoV-OC43 was detected by time-of-addition assay. The maximum tolerated dose of BLX and the influences of BLX on the body weight and survival time of suckling mice infected with HCoV-OC43 were determined. The expression of viral protein in the brain and lung tissue was analyzed by immunohistochemistry. ResultThere were 11 chemical components identified in BLX by UPLC-MS. BLX showed the 50% cytotoxic concentration （CC₅₀） of （13 859.56±319） mg·L^-1， the median inhibitory concentration （IC₅₀） of （1 439.09±200） mg·L^-1， and the selection index of 8.26-11.44 for HCoV-OC43 in HRT-18 cells. Compared with the cells infected with HCoV-OC43， BLX at the concentrations of 1 500， 1 000， 500 mg·L^-1 inhibited the proliferation of this virus （P<0.05， P<0.01）. BLX exhibited antiviral effect in the early stage of virus infection， and the inhibition role in the attachment stage was more significant than that in the entry stage （P<0.05）. In the suckling mice infected with HCoV-OC43， BLX at 1200 and 600 mg·kg^-1·d^-1 alleviated the symptoms， prolonged the survival period， reduced the death rate， and down-regulated the mRNA level of nucleocapsid protein in the mice. Moreover， BLX at 1 200 mg·kg^-1·d^-1 down-regulated the expression of nucleocapsid protein in the brain （P<0.01） and the lung （P<0.01）. ConclusionBLX contained multiple antiviral ingredients. It inhibited the proliferation of HCoV-OC43 both in vitro and in vivo by interference with viral attachment. This study provides theoretical reference for the treatment of acute respiratory tract infection with HCoV-OC43 and for further development and application of BLX.

The pathogenesis of depression is complex, and some existing monoamine antidepressants have problems such as drug resistance or off-target failure. Traditional Chinese medicine has the characteristics of "multi-component and multi-target", and has been used in the treatment of depression in clinical practice. Yueju pill is effective in the treatment of depression. Geniposide and ligustrazine, the active ingredients of Gardeniae fructus and Ligusticum sinense 'Chuanxiong', play a key role in the treatment of depression. In this study, based on the neuroprotective activity of genipin and the rapid antidepressant activity of tetramethylpyrazine, a series of novel genipin derivatives were designed and synthesized through pharmacophore assembly principle, and their neuroprotective activity and antidepressant effect were investigated. The results showed that the novel genipin derivatives had well neuroprotective activity on the glutamate-induced HT-22 cell model, with compounds W-1 and W-3 showing better protective activity. In behavioral despair depression (BDD) model mice, compound W-3 was found to have better antidepressant activity than W-1 in tail suspension test and forced swimming test. Further study on the behavior of chronic unpredictable mild stress (CUMS) model mice showed that W-3 could significantly improve the depression-like behavior of model mice. All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2022027). The effects of the preferred compound W-3 on protein kinase A (PKA), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine 1A (5-HT_1A) receptor, N-methyl-D-aspartate ionic glutamate receptor 2A (GluN2A) and N-methyl-D-aspartate ionic glutamate receptor 2B (GluN2B) were analyzed by Western blot. W-3 treatment significantly up-regulated the protein expression of PKA, CREB, BDNF and 5-HT_1A, and down-regulated the protein expression of GluN2A and GluN2B. The results of qRT-PCR were consistent with those of Western blot. According to the above results, compound W-3 has a potential antidepressant effect, and its mechanism may be related to the activation of PKA-CREB-BDNF signaling pathway by regulating the expression of GluN2A, GluN2B and 5-HT_1A receptor proteins.