ObjectiveTo explore the potential mechanism of Xiezhuo Jiedu prescription in regulating autophagy in the treatment of ulcerative colitis （UC） by bioinformatics and animal experiments. MethodsThe differentially expressed genes （DEGs） in the colonic mucosal tissue of UC patients was obtained from the Gene Expression Omnibus （GEO）， and those overlapped with autophagy genes were obtained as the differentially expressed autophagy-related genes （DEARGs）. DEARGs were imported into Metascape and STRING， respectively， for gene ontology/Kyoto Encyclopedia of Genes and Genomics （GO/KEGG） enrichment analysis and protein-protein interaction （PPI） analysis. Finally， 15 key DEARGs were obtained. The core DEARGs were obtained by least absolute shrinkage and selection operator （LASSO） regression and receiver operating characteristic curve （ROC） analysis. The CIBERSORT deconvolution algorithm was used to analyze the immunoinfiltration of UC patients and the correlations between core DEARGs and immune cells. C57BL/6J mice were assigned into a normal group and a modeling group. The mouse model of UC was established by free drinking of 2.5% dextran sulfate sodium. The modeled mice were assigned into low-， medium-， and high-dose Xiezhuo Jiedu prescription and mesalazine groups according to the random number table method and administrated with corresponding agents by gavage for 7 days. The colonic mucosal morphology was observed by hematoxylin-eosin staining. The protein and mRNA levels of cysteinyl aspartate-specific proteinase 1 （Caspase-1）， cathepsin B （CTSB）， C-C motif chemokine-2 （CCL2）， CXC motif receptor 4 （CXCR4）， and hypoxia-inducing factor-1α （HIF-1α） in the colon tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultsThe dataset GSE87466 was screened from GEO and interlaced with autophagy genes. After PPI analysis， LASSO regression， and ROC analysis， the core DEARGs （Caspase-1， CCL2， CTSB， and CXCR4） were obtained. The results of immunoinfiltration analysis showed that the counts of NK cells， M0 macrophages， M1 macrophages， and dendritic cells in the colonic mucosal tissue of UC patients had significant differences， and core DEARGs had significant correlations with these immune cells. This result， combined with the prediction results of network pharmacology， suggested that the HIF-1α signaling pathway may play a key role in the regulation of UC by Xiezhuo Jiedu prescription. The animal experiments showed that Xiezhuo Jiedu prescription significantly alleviated colonic mucosal inflammation in UC mice. Compared with the normal group， the model group showed up-regulated protein and mRNA levels of caspase-1， CCL2， CTSB， CXCR4， and HIF-1α， which were down-regulated after treatment with Xiezhuo Jiedu prescription or mesalazine. ConclusionCaspase-1， CCL2， CTSB， and CXCR4 are autophagy genes that are closely related to the onset of UC. Xiezhuo Jiedu prescription can down-regulate the expression of core autophagy genes to alleviate the inflammation in the colonic mucosa of mice.

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

ObjectiveThe bioinformatics method was used to screen ferroptosis differential genes （FRGs） closely related to ulcerative colitis （UC）， and animal experiments were conducted to verify whether the mechanism of Xiezhuo Jiedu recipe in treating UC is related to the regulation of ferroptosis. MethodThe differentially expressed genes （DEGs） of colonic mucosa tissue of UC patients were obtained from the GEO database， and the intersection of the genes with ferroptosis genes was used to obtain FRGs. The core FRGs were obtained by cluster analysis， minimum absolute contraction and selection operator （LASSO） regression， and receiver operating characteristic curve （ROC） curve analysis. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhuo Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of E3 ubiquitin ligase （FBXW7）， zinc finger protein （ZFP36）， solute carrier family 7 member 11 （SLC7A11）， and Toll-like receptor 4 （TLR4） in colon tissue. The protein expression levels of FBXW7， ZFP36， SLC7A11， and TLR4 in colon tissue were detected by Western blot. ResultDataset GSE87466 was screened from the GEO database， and its intersections with the ferroptosis gene were analyzed to obtain 21 FRGs. After cluster analysis， LASSO regression， and ROC analysis， core FRGs （FBXW7， ZFP36， SLC7A11， and TLR4） were obtained. Immunoinfiltration analysis showed significant differences in the expression of initial B cells， M1 macrophages， plasma cells， and M2 macrophages in the colonic mucosa tissue of UC mice， and there was a significant correlation between core FRGs and these immune cells. Further animal experiments showed that the colonic mucosa tissue of mice in the model group was disorganized and infiltrated by a large number of inflammatory cells. The inflammation of the colonic mucosa tissue of mice in each group was relieved to varying degrees after treatment with Xiezhuo Jiedu recipe and mesalazine， while the colonic mucosa tissue of mice in the high-dose group of Xiezhuo Jiedu recipe showed almost no inflammatory changes. Compared with the normal group， the protein and mRNA expressions of FBXW7， ZFP36， SLC7A11， and TLR4 in the model group were significantly increased， and the expression of core FRGs in colonic mucosa tissue of mice in all groups was significantly down-regulated after treatment with Xiezhuo Jiedu recipe and mesalazine. ConclusionFBXW7， ZFP36， SLC7A11， and TLR4 are ferroptosis genes closely related to the pathogenesis of UC， and Xiezhuo Jiedu recipe can significantly alleviate colonic mucosa inflammation in mice by down-regulating core ferroptosis genes.

Stroke flaccid paralysis is stroke patients with abnormal physical movement function and muscle tone decline as the main performance and is a kind of common pathological state after apoplectic stroke. The longer the flaccid paralysis is, the worse the prognosis. The theory of TCM holds that stroke is mainly due to "deficiency, wind, fire, phlegm, stasis, qi", and when the pathogenic factor accumulate and block the meridians, which would cause blood stagnation, muscle and tendon damage and flaccidity, resulting in stroke paralysis. Therefore, it is necessary to set up the "Tongjing Roujin" (stimulating the muscle and nourishing the tendon) as its main treatment. Fire-needling has the effect of stimulating muscle, warming yang, nourishing tendon, and relieving pain in the treatment of stroke flaccid paralysis. It can warm yang and dissipate cold, replenish and nourish meridian qi, release muscle nodules, promote the circulation of qi and blood, and nourish all limbs and bones. Fire-needling therapy can promote the recovery of neural pathway, strengthen local metabolism, improve local muscle tension, and thus restore limb function. The high-quality clinical research, acupoint selection rules, and standardized operating techniques of fire-needling treatment for stroke flaccid paralysis need to be further deepened.

BACKGROUND:The distribution of the necrotic area plays an important role in hip preservation treatment.At present,there are few studies on whether the difference in the three-dimensional spatial distribution of osteonecrosis of the femoral head affects the clinical outcome of fibular support. OBJECTIVE:To explore the relationship between the spatial distribution and clinical outcome at the sites of osteonecrosis of the femoral head and fibular support using CT three-dimensional reconstruction so as to provide a basis for optimizing the applicable conditions of fibular support and improving the hip preservation effect of fibular support. METHODS:Eighty patients with osteonecrosis of the femoral head who were treated with fibular support for hip preservation from January 2010 to January 2021 were selected as the study subjects according to the inclusion criteria.They were followed up for at least 2 years.According to the clinical outcome,the patients were divided into the successful hip preservation group(n=55)and the failure hip preservation group(n=25).3D reconstruction was performed according to the preoperative and postoperative CT images of the patients.According to the three-column theory,the femoral head was divided into outer nine areas,middle nine areas and inner nine areas(L1-9,C1-9,and M1-9)to explore the spatial distribution of necrotic area of the femoral head and fibular support area and its relationship with clinical outcome. RESULTS AND CONCLUSION:(1)Before operation,the necrotic area of the femoral head was mainly distributed in L1,L2,L4,L5,C1,C2,C4,and C5(the upper and middle part of the anterior part of the outer ninth area and the middle part of the middle ninth area).After operation,the fibular support area was mainly distributed in L5,L6,C5,and C6(the middle and lower part of the outer ninth area and the middle and lower part of the middle ninth area).(2)There were significant differences in the distribution of osteonecrosis of the femoral head between the successful hip preservation group and the failure hip preservation group in L8(the posterior middle part of the outer ninth area),C3(the anterior lower part of the middle ninth area),C6(the lower middle part of the middle part of the inner ninth area)and M2(the anterior middle part of the inner ninth area)(P<0.05).There was a significant difference in the distribution of fibular support in L5 and L6(middle and lower part of outer nine)(P<0.05).Among them,the L8 region could be used as an independent predictor of hip preservation failure in fibular support surgery.The area under the curve of the L8 single factor prediction model was 0.698[95%CI(0.575,0.822)];the sensitivity was 76%,and the specificity was 63.6%.(3)It turns out,when the necrotic area involves L8,C3,C6,and M2,especially L8,the failure of fibular support may increase,and when the fibular support involves L5 and L6,the effect of hip preservation is often not ideal.

BACKGROUND:Bone has bioelectric effects.However,bone defects can lead to loss of endogenous bioelectricity in bone.The implantation of bone tissue engineering scaffolds with bioelectric effect into bone defects will replenish the missing electrical signals and accelerate the repair of bone defects. OBJECTIVE:To introduce the bioelectric effect of bone tissue and expound the repair effect of electrical stimulation on bone defects,summarize the research progress of bioelectric effect applied to bone tissue engineering,in order to provide new ideas for the research of bone tissue engineering. METHODS:Relevant articles were searched on CNKI,WanFang,PubMed,Web of Science and ScienceDirect databases,using"bioelectrical effect,bioelectrical materials,electrical stimulation,bone tissue engineering,bone scaffold,bone defect,bone repair,osteogenesis"as the English and Chinese search terms.Finally,87 articles were included for analysis. RESULTS AND CONCLUSION:(1)Bioelectrical effect combined with ex vivo electrical stimulation to design bone tissue engineering scaffolds is an ideal and feasible approach,and the main materials involved include metallic materials,graphene materials,natural bio-derived materials,and synthetic biomaterial.At present,the most widely used conductive material is graphene material,which benefits from its super conductivity,large specific surface area,good biocompatibility with cells and bones,and excellent mechanical properties.(2)Graphene materials are mainly introduced into the scaffold as modified materials to enhance the conductivity of the overall scaffold,while its large surface area and rich functional groups can promote the loading and release of bioactive substances.(3)However,there are still some major challenges to overcome for bioelectrically effective bone tissue engineering scaffolds:not only electrical conductivity but also the overall performance of the bracket needs to be considered;lack of uniform,standardized preparation of bioelectrically effective bone tissue engineering scaffolds;extracorporeal electrical stimulation intervention systems are not yet mature enough;lack of individualized guidance on stent selection to enable the selection and design of the most appropriate stent for patients with different pathologies.(4)When designing conductive scaffolds,researchers have to deeply consider the comprehensive effects of the scaffolds,such as biocompatibility,mechanical properties,and biodegradability.This combination of properties can be achieved by combining multiple materials.(5)Beyond that,clinical translation should be the ultimate consideration for conductive stent design.On the basis of evaluating the safe current threshold for electrical stimulation to act on the human body and facilitate the repair of bone defects,animal experiments as well as basic experiments are designed and then applied to the clinic to achieve the ultimate goal of applying bioelectrical effect bone tissue engineering scaffolds in the clinic.

Objective:To investigate the association of exposure to PM 2.5 and its constituents during pregnancy and fetal growth and to further identify critical windows of exposure for fetal growth. Methods:We included 4 089 mother-child pairs from the Jiangsu Birth Cohort Study between January 2016 and October 2019. Data of general characteristics, clinical information, daily average PM 2.5 exposure, and its constituents during pregnancy were collected. Fetal growth parameters, including head circumference (HC), abdominal circumference (AC), and femur length (FL), were measured by ultrasound after 20 weeks of gestation, and then estimated fetal weight (EFW) was calculated. Generalized linear mixed models were adopted to examine the associations of prenatal exposure to PM 2.5 and its constituents with fetal growth. Distributed lag nonlinear models were used to identify critical exposure windows for each outcome. Results:A 10 μg/m 3 increase in PM 2.5 exposure during pregnancy was associated with a decrease of 0.025 ( β=-0.025, 95% CI: -0.048- -0.001) in HC Z-score, 0.026 ( β=-0.026, 95% CI: -0.049- -0.003) in AC Z-score, and 0.028 ( β=-0.028, 95% CI:-0.052--0.004) in EFW Z-score, along with an increased risk of 8.5% ( RR=1.085, 95% CI: 1.010-1.165) and 13.5% ( RR=1.135, 95% CI: 1.016-1.268) for undergrowth of HC and EFW, respectively. Regarding PM 2.5 constituents, prenatal exposure to black carbon, organic matter, nitrate, sulfate (SO 42-) and ammonium consistently correlated with decreased HC Z-score. SO 42- exposure was also associated with decreased FL Z-scores. In addition, we found that gestational weeks 2-5 were critical windows for HC, weeks 4-13 and 19-40 for AC, weeks 4-13 and 23-37 for FL, and weeks 4-12 and 20-40 for EFW. Conclusions:Our findings demonstrated that exposure to PM 2.5 and its constituents during pregnancy could adversely affect fetal growth and the critical windows for different fetal growth parameters are not completely consistent.

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides (MOIG) on bone loss of rheumatoid arthritis (RA) rats, and the mechanism of osteoclast function and activity induced by lipopolysaccharide (LPS). RA rats were established by injecting bovin type II collagen. The Bio-ethic Committee of Zhejiang Chinese Medical University approved all experimental protocols associated with this study (IACUC-20180410-03). The collagen-induced arthritis (CIA) rats were administered drug by gavage for 8 weeks; the femoral trabecular micro-structure changes were observed in CIA rats by micro-CT; the LPS-induced osteoclasts model further observed the effect and mechanism of anti-inflammatory osteoporosis in vitro. The results indicated that MOIG could markedly increase bone mineral density (BMD) in CIA rats, improve trabecular micro-structure. In vitro studies demonstrated that MOIG could significantly inhibit osteoclastogensis and differentiation, suppress tartrate resistant acid phosphatase (TRAP) activity, F-actin ring formation, TNF receptor associated factor 6 (TRAF6) recruitment, and inhibitor of nuclear factor kappa-Bα (IκBα) degradation as well as p65 phosphorylation, thereby repressing nuclear factor kappa-B (NF-κB) signaling pathway activation. Subsequently, MOIG effectively inhibited osteoclast nuclear factor of activated T-cells c1 (NFATc1) and cellular oncogene Fos (c-Fos) expression, as well as bone resorption related protein activity including matrix metalloprotein 9 (MMP-9) and cathepsin K (CtsK). Meanwhile, MOIG also repressed the phosphorylation expression of Janus activating kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), thereby inhibiting JAK2/STAT3 signaling pathway activation. Moreover, further studies found that MOIG could suppress glycogen synthase kinase-3β (GSK-3β) activity, and GSK-3β gene silencing could markedly inhibit oetsoclast F-actin ring formation as well as the phosphorylation expression of p65 and STAT3. Of note, compared with GSK-3β gene silencing group, there was no significant difference in the group treated with both MOIG with GSK-3β gene silencing simultaneously. Thus, the results suggested that MOIG may inhibit NF-κB signaling pathway and JAK2/STAT3 signaling pathway activation via regulating GSK-3β, thereby alleviating bone destruction in RA.

Objective:To investigate the effects of early postoperative nutritional management under enhanced recovery after surgery (ERAS) guidelines on nutritional biochemical indicators and length of hospital stay in patients undergoing lumbar fusion surgery. Method:Ninety-four patients who underwent lumbar posterior internal fixation + intervertebral fusion surgery in Department of Orthopedics Ⅲ of Ningxia Medical University General Hospital from January 2020 to March 2021 were randomly divided into an intervention group (n=47) and a control group (n=47). The intervention group received nutritional intervention by a clinical nutritionist at 2 hours after anesthesia recovery, and the control group started to eat liquid diet at 6 hours after anesthesia recovery. The protein-calorie intake, blood glucose, total protein, albumin, hemoglobin, postoperative hospitalization time and total hospitalization time of the two groups were observed. Results:The protein-calorie intake of the intervention group was higher than that of the control group on the day of surgery and the first 3 days after surgery, with statistically significant differences (P<0.05). The blood glucose level of the intervention group was lower than that of the control group on the first day after surgery, with statistically significant differences (P<0.05). The total protein level of the intervention group was higher than that of the control group on the third day after surgery, with statistically significant differences (P<0.05). The albumin and hemoglobin levels of the intervention group were higher than those of the control group on the first and third days after surgery, with statistically significant differences (P<0.05). The incidence of abdominal distension and the length of hospital stay in the intervention group were lower than those in the control group, with statistically significant differences (P<0.05). Conclusion:Early postoperative nutritional management has a certain effect on improving nutritional and biochemical indicators and shortening the length of hospital stay in patients undergoing lumbar fusion surgery.

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]