Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

This paper aimed to study phenylpropanoids of Tripterygium hypoglaucum. Twenty-four compounds were isolated from the 70% EtOH extracts of T. hypoglaucum by silica gel column chromatography, reversed phase column chromatography, gel column chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography. Compounds 1-3 were three new phenylpropionds. Their structures were identified by ultraviolet spectrum, infrared spectroscopy, high resolution electrospray ionization mass spectrometry, and nuclear magnetic resonance data as: threo-2-(4-hydroxy-3-methoxyphenoxy)-3-(4-hydroxy-3-methoxyphenyl)-1,3-propanedol (1), erythro-2-(4-hydroxy-3-methoxyphenoxy)-3-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (2), erythro-3-(4-hydroxy-3,5-dimethoxyphenyl)-3-ethoxypropane-1,2-propanediol (3). Compounds 4-6, 9, 14, 15, 18, 19, and 21-24 were obtained from Tripterygium genus for the first time. The cytotoxicity assay of cancer cells suggested that compound 20 displayed cytotoxicity on the breast cancer 4T1 cells whose 50% inhibitory concentration was 125.60 μmol·L^-1.

Objective To summarize the prescription and medication rules for the treatment of diabetes mellitus by contemporary Lingnan famous Chinese medical practitioners through data mining analysis.Methods The literature on treating diabetes mellitus by contemporary Lingnan famous Chinese medical practitioners were retrieved from the databases of CNKI,Wanfang and VIP,and the collections of clinical experience and medical cases of contemporary Lingnan famous practitioners were also reviewed to screen the relevant medical records of diabetes mellitus treated by Lingnan famous practitioners.The information of Chinese medicine prescriptions for diabetes mellitus in the medical records was input to Excel to establish a database,and then the frequency analysis was performed in terms of the nature,flavors and meridian tropism,therapeutic-action classification of the Chinese herbal medicines and traditional Chinese medicine(TCM)syndrome types.Moreover,the association rule analysis and cluster analysis were carried out using IBM SPSS Modeler 18.0 and SPSS Statistics 26.0.Results A total of 62 medical records of diabetes mellitus treated by the 24 contemporary Lingnan famous Chinese medical practitioners such as DENG Tie-Tao,LIU Shi-Chang,XIONG Man-Qi,LI Sai-Mei,ZHU Zhang-Zhi,LIU Min,and FAN Guan-Ji were screened out for the analysis.And a total of 101 prescriptions involving 210 Chinese herbal medicines were included.There were 29 commonly-used Chinese medicines with a frequency being or more than 15 times,and they were Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Astragali Radix,Bupleuri Radix,Puerariae Lobatae Radix,Poria,Atractylodis Macrocephalae Rhizoma,Codonopsis Radix,Scutellariae Radix,etc.According to the therapeutic action,the Chinese medicines were mainly classified into the categories of drugs for supplementing the deficiency,drugs for clearing heat,and drugs for dispelling wind-damp.The primary syndrome types were syndrome of deficiency of both spleen and kidney and syndrome of liver stagnation and spleen deficiency,and the syndromes were usually complicated with the syndrome elements of qi deficiency,yin deficiency,yang deficiency,cold-damp,phlegm-damp,and damp-heat.The association rule analysis yielded 28 core drug combinations consisting of 2-4 herbs,and the cluster analysis yielded 5 new candidate prescriptions,which were mainly derived from the modification of classical formulas such as Xiao Chaihu Decoction,Fuzi Lizhong Decoction,Yuquan Pills plus Zengye Decoction,and Zuogui Pills.Conclusion For the treatment of diabetes mellitus,contemporary Lingnan famous Chinese medical practitioners primarily adopt the methods of invigorating spleen and warming kidney,and soothing liver,draining dampness and resolving turbidity,which has more distinctive regional characteristics of Lingnan and can provide a reference for syndrome differentiation and treatment of diabetes mellitus in the Lingnan area.

Objective To compare the clinical characteristics,peripheral blood inflammatory cells and levels of oxidative stress indicators between severe asthma and non-severe asthma patients,analyze the effects of neutrophils and oxidative stress molecules on the severity of asthma,and build a biological model for early prediction of severe asthma.Methods From Aug 2018 to Jul 2019,67 adult patients with stable asthma in our hospital were enrolled in this study.The clinical characteristics,peripheral blood inflammatory cells and levels of oxidative stress indicators of severe asthma group and non-severe asthma group were compared.Single factor Logistic regression analysis was conducted on severe asthma to screen out the most important five variables.Multifactor Logistic regression analysis was further conducted to establish a prediction model for severe asthma.Results There were 25 severe asthma patients in this cohort,who had a longer course of disease,more frequent acute attacks,poorer asthma control,higher peripheral neutrophils,more severe obstructive ventilation dysfunction,lower myeloperoxidase(MPO)level and higher superoxide dismutase(SOD)than non-severe asthma patients.The patients with higher peripheral blood neutrophil count or proportion were more likely to show severe asthma,more frequent acute attacks,and more obvious reduction of pulmonary ventilation function.A panel of biomarkers,centered on peripheral blood neutrophil count and oxidative stress indicators SOD,human 8-epi-prostaglandin F2α(8-iso-PGF2α),could build a model to predict severe asthma.Conclusion There are significant differences in clinical characteristics,peripheral blood inflammatory cells,and oxidative stress index levels between severe asthma patients and non-severe asthma patients.In stable asthma patients,levels of neutrophils and oxidative stress indicators such as SOD had an impact on the severity of asthma.The prediction model of severe asthma established on this basis provides a new idea for early recognition of severe asthma.

Purpose::The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.Methods::We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant. Results::Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F= 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F= 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F= 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F= 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F= 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F= 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression. Conclusions::CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Objective To investigate the role of necroptosis key genes in spinal cord injury using bioinformatics methods to provide new targets for the diagnosis and treatment of spinal cord injury.Methods The peripheral blood transcriptome data of spinal cord injury samples(n=38)and healthy control samples(n=10)were obtained from GSE151371 data set in Gene Expression Omnibus(GEO)database.R software was used to identify differentially expressed genes and perform functional enrichment analysis.Machine learning algorithms(random forest and LASSO)and protein-protein interaction(PPI)networks are used to screen for necroptosis key genes and construct a diagnostic nomogram for spinal cord injury.Establish a rat spinal cord injury model to further verify the expression of necroptosis key genes by Western blotting and immunofluorescence staining.Results A total of 2050 differentially expressed genes were identified in the two groups.KEGG pathway enrichment analysis showed that the differentially expressed genes were involved in the nucleotide-binding oligomerization domain(NOD)-like receptor signaling pathway,hematopoietic cell lineage,and necroptosis;GO enrichment analysis showed that the differentially expressed genes were involved in the activation of leukocytes,tertiary granulation,and regulation of the defense response,and so on.Intersection analysis screened 15 necroptosis differentially expressed genes.KEGG pathway enrichment analysis showed that necroptosis differentially expressed genes were involved in necroptosis,influenza,and NOD-like receptor signaling pathways;GO enrichment analysis showed that necroptosis differentially expressed genes were significantly enriched in the cellular response to cytokine stimulation,cytokine-mediated signaling pathways,and response to cytokines.Integration of two machine learning algorithms and PPI analysis further screened two necroptosis key genes(IL1B and PLA2G4A).The nomogram established using IL1B and PLA2G4A can be used for early prediction of the occurrence of spinal cord injury.The validation results of the rat spinal cord injury model showed that the protein expression of IL-1β and PLA2G4A in the spinal cord injury group were significantly higher than those in the sham group(P<0.05).Conclusions IL1B and PLA2G4A as key genes of necroptosis involved in the development of spinal cord injury,can be used to predict the development of spinal cord injury with the promise of being new targets for the prevention and treatment of spinal cord injury.

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]

Objective To study the clinical characteristics and bacterial antimicrobial susceptibility testing results of patients with clinically isolated Ralstonia pickettii(R.pickettii),and provide basis for the rational use of antimi-crobial agents.Methods Inpatients with R.pickettii infection who were treated at the Tianjin First Central Hospi-tal from January 2014 to December 2023 were analyzed retrospectively.Clinical characteristics and antimicrobial sus-ceptibility testing results were analyzed.Results A total of 80 strains of Ralstonia spp.were isolated over 10-year period,including 42(52.5％)non-repetitive strains of R.pickettii.Among 42 R.pickettii strains,64.3％were isolated from male patients.The strains isolated from sputum,catheter,blood,throat swabs,and drainage fluid specimens accounted for 38.1％,28.6％,19.0％,4.8％,and 2.4％,respectively.The clinical distribution of R.pickettii was highest in the intensive care unit(ICU),with a proportion of 52.4％.The number of infected patients first increased and then decreased with the years,followed by a slight fluctuation.There was no statistically signifi-cant difference in the number of infected patients in each department over the years(P＞0.05).R.pickettii had higher susceptibility rates to doxycycline,levofloxacin,ciprofloxacin,and minocycline,susceptibility rates were 78.3％-90.9％,but was completely resistant to compound sulfamethoxazole and cefazolin(100％),it also had higher resistance rates to aztreonam,colistin,cefotetan,tobramycin,amikacin,ceftazidime,and gentamicin(80.0％-97.4％).There was no statistically significant difference in the resistance rates to 21 antimicrobial agents among different years(all P＞0.05).Conclusion R.pickettii is mainly from ICU,and the majority of the infected population are adult males.Most strains are isolated from sputum and catheter.R.pickettii presents multidrug re-sistance.Attention should be paid to the changes in the resistance rates of antimicrobial agents,strengthen the dy-namic monitoring of bacterial resistance and guide the rational selection of antimicrobial agents in clinic,implement early and effective treatment to improve the prognosis of the patients.

Objective:To investigate possible mechanism on protien LMP1 expressed by EBV inducing plasmablast differentiation of DLBCL cell via the mTORC1 pathway.Methods:The expression levels of LMP1 protein,CD38 and the phosphorylation levels of p70S6K in EBV+and EBV-DLBCL cell lines were detected by Western blot.Cell lines overexpressing LMP1 gene stablely were constructed and LMP1 gene was silenced by RNAi.The expression of LMP1 gene was verified by RT-qPCR.The expression levels of LMP1 and CD38 and the phosphorylation levels of p70S6K in each group were detected by Western blot.Results:Compared with EBV-DLBCL cells,the expression of LMP1 was detected on EBV+DLBCL cells(P=0.0008),EBV+DLBCL cells had higher phosphorylation levels of p70S6K(P=0.0072)and expression levels of CD38(P=0.0091).Compared with vector group,the cells of LMP1OE group had higher expression levels of LMP1 and CD38(P=0.0353;P＜0.0001),meanwhile molecular p70S6K was phosphorylated much more(P=0.0065);expression of LMP1 mRNA was verified(P＜0.0001).Compared with si-NC group,expression level of LMP1 protein(P=0.0129)was not detected and phosphorylated p70S6K disappeared of LMP1KO group(P=0.0228);meanwhile,expression of CD38 decreased,although there was no significant difference(P=0.2377).Conclusion:LMP1 promotes DLBCL cells plasmablast differentiation via activating mTORC1 signal pathway.

Aim To observe the effects of Wenfei Jiangzhuo formula(WFJZF)on rats with vascular de-mentia and investigate its possible mechanism of ac-tion.Methods Thirty-six healthy male SD rats were randomly divided into the sham group,model group,donepezil group,and low-dose,medium-dose and high-dose groups of Wenfei Jiangzhuo formula,with six rats per group.Except for the sham group,the other groups were prepared as VaD models,and each group was gavaged with the corresponding drugs after suc-cessful modeling,and tests were performed after three weeks of treatment.Behavioral,hippocampal CA1 area morphology,neural dendrites and mitochondrial chan-ges were observed in all groups of rats,and phospho-glycerate mutase 5(PGAM5),dynamics-related pro-teins1(Drp1),opticatrophyprotein-1(OPA1),and other proteins were detected in each group.Results Compared with the sham group,rats in the model group and each intervention group had prolonged es-cape latency(P＜0.05),a shorter number of travers-als across the platforms(P＜0.05),a sparse morphol-ogy of hippocampal neurons,a reduction in the number of secondary dendritic spines,and a rupture of the out-er membrane of the mitochondria;the expression of the PGAM5 and Drp1 proteins in hippocampal tissues was elevated(P＜0.05),and the expression of the OPA1 and Mfn1/2 protein expression decreased(P＜0.05);compared with the model group,donepezil group and Wenfei Jiangzhuo formula high-dose group of rats had shorter evasion latency(P＜0.05),increased number of times to traverse the platform(P＜0.05),increased number of hippocampal neurons,tightly packed,more secondary dendritic structures,and reduced mitochon-drial damage;the expression of PGAM5 and Drp1 pro-teins was reduced(P＜0.05),and the expression of OPA1 and Mfn1/2 proteins was elevated(P＜0.05).Conclusions Wenfei Jiangzhuo formula can regulate the PGAM5-Drp1 signaling axis to improve the balance of mitochondrial homeostasis,thus improving the cog-nitive condition of the brain and exerting cerebroprotec-tive effects.