ObjectiveTo elucidate the efficacy connotation of Shudi Qiangjin pills （SQP） against liver and kidney deficiency in steroid-induced osteonecrosis of femoral head （SONFH） from the perspective of the "disease-syndrome-formula" association and to clarify the underlying mechanisms based on in vivo and in vitro experiment validation. MethodsThe chemical components and the corresponding putative targets of SQP were collected from the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0， the Encyclopedia of Traditional Chinese Medicine （ETCM） v2.0， and HERB databases. The SONFH-related genes were identified based on the differential expression profiles of peripheral blood of patients with SONFH compared to the healthy volunteers， and the disease phenotype-related targets were collected from the TCMIP v2.0 database. Then， the interaction network of "SONFH-related genes and candidate targets of SQP" was constructed based on "gene-gene interaction information"， and the major network targets were screened by calculating the topological characteristic values of the network followed by the functional mining according to the Kyoto Encyclopedia of Genes and Genomes （KEGG） database and the SoFDA database. After that， the SONFH rat model was prepared by lipopolysaccharide combined with methylprednisolone injection， and 2.5， 5， 7.5 g·kg^-1 SQP （once per day， equivalent to 1， 2， and 3 times the clinical equivalent dose， respectively） or 7.3×10^-3 g·kg^-1 of alendronate sodium （ALS， once per week， equivalent to the clinical equivalent dose） was given for 8 weeks. The effect characteristics of SQP and ALS in the treatment of SONFH were evaluated by micro-computed tomography scanning， hematoxylin and eosin staining， alkaline phosphatase （ALP） staining， immunohistochemical staining， enzyme-linked immunosorbent assay， and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling（TUNEL）staining， and a comparative efficacy analysis was conducted with ALS. In addition， SONFH cell models were prepared by dexamethasone stimulation of osteoblasts， and the intervention was carried out with the medicated serum of SQP at the aforementioned three doses. Cell counting kit-8， ALP staining， ALP activity assay， alizarin red staining， and flow cytometry were employed to investigate the regulatory effect of SQP on osteoblasts. The expression levels of osteogenesis-related proteins and key factors of the target signaling axis were detected by quantitative real-time polymerase chain reaction and Western blot. ResultsThe network analysis results demonstrated that the candidate targets of SQP primarily exerted their therapeutic effects through key signaling pathways， including phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt）， lipid metabolism and atherosclerosis， prolactin， chemokines， and neurotrophic factors pathways. These pathways were significantly involved in critical biological processes such as muscle and bone metabolism and the regulation of the "neuro-endocrine-immune" network， thereby addressing both modern medical symptoms （e.g.， delayed skeletal maturation and recurrent fractures） and traditional Chinese medicine （TCM） symptoms （e.g.， fatigue， aversion to cold， cold limbs， and pain in the limbs and joints in patients with SONFH characterized by liver and kidney deficiency syndrome. Among these pathways， the PI3K/Akt signaling pathway exhibited the highest degree of enrichment. The in vivo experimental results demonstrated that starting from the 4^th week after modeling， the modeling group exhibited a significant reduction in body weight compared to the control group （P<0.05）. After six weeks of treatment， all dosage groups of SQP showed significantly higher body weights compared to the model group （P<0.01）. Compared with the normal group， the model group exhibited significant decreases in bone mineral density （BMD）， bone volume fraction （BV/TV）， trabecular number （Tb.N）， osteocalcin （OCN）， alkaline phosphatase （ALP） levels in femoral head tissue， and serum bone-specific alkaline phosphatase （BALP） （P<0.01）， along with significant increases in trabecular separation （Tb.Sp）， empty lacunae rate in tissue， and apoptosis rate （P<0.01）. In comparison to the model group， the SQP intervention groups showed significant improvements in BMD， BV/TV and Tb.N （P<0.01）， significant reductions in Tb.Sp， empty lacunae rate and apoptosis rate （P<0.05）， and significant increases in protein levels of OCN and ALP as well as BALP content （P<0.05）. The in vitro experimental results revealed that all dosage groups of SQP medicated serum showed no toxic effects on osteoblast. Compared with the normal group， the model group displayed significant suppression of osteoblast proliferation activity， ALP activity， and calcified nodule formation rate （P<0.01）， significant decreases in mRNA transcription levels of OCN and Runt-related transcription factor 2 （RUNX2） （P<0.01）， significant reductions in protein content of osteopontin （OPN）， typeⅠ collagen （ColⅠ）A1， B-cell lymphoma-2 （Bcl-2）， PI3K， and phosphorylated （p）-Akt （P<0.01）， and a significant increase in apoptosis rate （P<0.01）. Compared with the model group， the SQP medicated serum intervention groups exhibited significant increases in proliferation activity， ALP activity， calcified nodule formation rate， mRNA transcription levels of OCN and RUNX2， and protein content of OPN， ColⅠA1， Bcl-2， PI3K， and p-Akt （P<0.05）， along with a significant decrease in apoptosis rate （P<0.01）. ConclusionSQP can effectively reduce the disease severity of SONFH with liver and kidney deficiency syndrome and improve bone microstructure， with the therapeutic effects exhibiting a dose-dependent manner. The mechanism may be related to its regulation of key processes such as muscle and bone metabolism and the correction of imbalances in the "neuro-endocrine-immune" network， thereby promoting osteoblast differentiation and inhibiting osteoblast apoptosis. The PI3K/Akt signaling axis is likely one of the key pathways through which this formula exerts its effects.

N-acetyl-p-aminophenol （APAP） is an antipyretic analgesic commonly used in clinical practice， and APAP overdose can cause severe liver injury and even death. In recent years， the incidence rate of APAP-induced liver injury （AILI） tends to increase， and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI， involving the mechanisms such as APAP protein conjugates， oxidative stress， JNK activation， mitochondrial dysfunction， inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI， in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.

Autoimmune hepatitis(AIH)is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system,and with the prolongation of disease course,it may gradually progress to liver cirrhosis and even hepatocellular carcinoma.Although great achievements have been made in the understanding and treatment of AIH,its etiology and pathogenesis still remain unclear.T cells play a crucial role in the development and progression of AIH,and by focusing on follicular helper T cells,this article elaborates on the research advances in follicular helper T cells in AIH,in order to provide new ideas and strategies for the clinical treatment of AIH.

Autoimmune hepatitis(AIH)is chronic hepatitis caused by the attack of live cells by the immune system,and at present,the pathogenesis of AIH remains unclear.Inflammasomes are important components of innate immunity and are involved in a variety of pathophysiological processes.Studies have shown that inflammatory response associated with nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)plays an important role in the pathogenesis of AIH,which mainly mediates the release of proinflammatory factors and pyroptosis,thereby participating in the pathophysiological process of AIH.Therefore,the development and progression of AIH can be delayed by inhibiting the activation of NLRP3 inflammasomes,which provides new ideas for the prevention and treatment of AIH.

Objective To investigate the effect and mechanism of emodin on focal cerebral ischemia in rats based on myeloid differentiation factor 88(MyD88)/extracellular signal-regulated kinase(ERK)pathway and nuclear factor-κB(NF-κB)nuclear translocation.Methods SD rats were randomly divided into sham operation group,model group and emodin group,with six rats in each group.The rat model of transient middle cerebral artery occlusion(tMCAO)was established by middle cerebral artery embolization.Rats in the emodin group were given 40 mg·kg-1 emodin by gavage for three times at 72,48 and 24 hours before modeling.At 24 hours after modeling,the neurological function of rats was scored.TTC staining was used to detect the area of cerebral infarction.HE staining was used to observe the morphological changes of brain tissue.The mRNA expression levels of MyD88 and tumor necrosis factor-α(TNF-α)in brain tissue were detected by RT-qPCR.The expression levels of MyD88,ERK,p-ERK and TNF-α in brain tissue were detected by Western Blot.The protein expression of NF-κB in brain tissue was detected by immunofluorescence.Results Compared with the sham operation group,the neurological function score of the model group was significantly increased(P＜0.01),and the cerebral infarction area was significantly increased(P＜0.01).In the cortical area of the ischemic penumbra,cell necrosis,abnormal cell morphology,nuclear fragmentation and atrophy,and the number of cells decreased significantly;the mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly increased(P＜0.01,P＜0.001),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly increased(P＜0.05,P＜0.01,P＜0.001),and the proportion of NF-κB into nuclear cells was significantly increased(P＜0.001).Compared with the model group,the neurological function score of rats in the emodin group was significantly decreased(P＜0.05),and the area of cerebral infarction was significantly reduced(P＜0.05).The number and morphology of neurons in the ischemic penumbra cortex were restored to a certain extent.The mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly decreased(P＜0.05,P＜0.01),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly decreased(P＜0.05),and the proportion of NF-κB into nuclear cells was significantly decreased(P＜0.001).Conclusion Emodin has a preventive and protective effect on rats with focal cerebral ischemia,which may be related to its inhibition of MyD88 activation,ERK phosphorylation and NF-κB nuclear translocation,and then down-regulation of inflammatory cascades and secretion of pro-inflammatory factors such as TNF-α,thereby exerting anti-inflammatory effects.

The mini-midline catheter is a new technology for catheter placement that opens up a new field of peripheral venous access devices(PVADs)and plays an important role in the intravenous treatment of patients with fragile vasculature and difficult intravenous access(DIVA).Mini-midline catheter is more economical and easier to puncture than midline catheter,longer retention time than short cannula,lower catheter-related complications,it is the preferred solution for venous vascular access device(VAD)in short-to medium-term infusion and has been widely used in intravenous infusion abroad.Domestic research and application of this technology are still in the exploratory stage,and the specifications,guidelines and expert consensus for mini midline catheters have not yet been released,and there is a lack of standardized operation procedures,indications,contraindications and other guidelines.More studies with higher quality and multi-center linkage cooperation need to be carried out to provide a theoretical and practical basis for the formulation of industry standards for mini midline catheters in line with clinical practice.The definition,attributes,innovation,indications,advantages and disadvantages of the mini midline catheter were reviewed,so as to provide reference for clinical application.

Objective To study the possibility of salivary microbiota model to diagnose laryngopharyngeal re-flux(LPR).Methods A case-control study was applied to enroll 34 patients as case group who showed significant efficacy after 8 weeks of proton pump inhibitor treatment from February 2022 to November 2022.And 47 healthy volunteers matched by age,gender and body mass index with the case group were enrolled as the control group.Their salivary samples were collected before medication,and the salivary microbiota was detected by 16S rDNA se-quencing.Bioinformatics analysis was conducted on the sequencing results to compare species differences at the ge-nus level.A total of 24 patients and 33 cases in the control group were selected as train set and the rest as test set.Random forest method was used to classify data and ten fold cross validation was applied to select the optimal bacte-rial genus combination to construct a diagnostic model.The probability of disease(POD)index was calculated and receiver operating characteristic curve(ROC)was used to evaluate the diagnostic model in diagnosis of LPR.SPSS 18.0 software was utilized for statistical analysis.Results Compared with the control group,there was a statistical difference in the relative abundance of 22 genera in saliva between the case group and the control group(P＜0.05).A diagnostic model consisting of 6 genera was constructed,namely Lactobacillus,Novosphingobium,Bacillus,Pseudoalteromonas,Ralstonia and Phocaeicola.The area under the ROC curve of the test set was 0.843,the sensi-tivity of the diagnostic model was 60.0％,the specificity was 87.71％,and the Kappa value was 0.470.Conclusion The bacterial combination diagnostic model constructed from saliva microbiota based on microbiome and machine learning can effectively distinguish LPR patients from healthy individuals,which has potential clinical application value.

The cochlear implanting provides a significant positive effects to the treatment of hearing impair-ment.However,the postoperative speech perception outcomes are variable among patients.Given the importance of assessing patients'speech recovery following surgery,the implementation of an objective and precise evaluation methodology becomes crucial.This review gives a brief introduction to the advantages and limitations of traditional methods of speech assessment following cochlear implantation,and further discusses the principles,advantages,and limitations of functional near-infrared optical brain imaging(fNIRS),as well as its application in patients after co-chlear implantation,in order to offer insights for the assessment and rehabilitation of individuals after cochlear im-planted surgery.

Dengue virus(DENV)diseases are a serious threat to human life and health,and there is no effective vaccine for DENV in China.In this study,a recombinant subunit candidate vaccine for DENV-2 was prepared.Using the ED Ⅲ gene of DENV-2 as the target gene,the recombinant eu-karyotic expression plasmid was constructed and transfected into suspension cells to express the target protein.The appropriate immune dose was screened to immunize mice and the immunogenic-ity was analyzed.The recombinant eukaryotic expression vector of DENV was successfully con-structed and transfected into HEK-293F to express the target protein,which was about 15 kDa in size.The mice were immunized with different doses of recombinant protein mixed with aluminum salt as adjuvant and the immunogenicity was analyzed.On the 35th day after the first immuniza-tion,the serum specific antibody levels of mice in the three protein immunization groups were sig-nificantly higher than those in the adjuvant group and PBS group,and the specific antibody levels of 10 μg D2EDⅢ protein group and 20 μg D2EDⅢ protein group were 1.43 and 1.56 times higher than those of 5 μg D2EDⅢ protein group,respectively.The antibody typing was biased to IgG1,in-dicating that the recombinant subunit candidate vaccine of DENV-2 prepared in this study mainly improved humoral immune response,but there was no significant difference in IgG1 antibody levels among the three protein immunization groups.Considering the immune effect and vaccine cost,the optimal target protein immunization dose per mouse was determined to be 10 μg.In this study,a recombinant subunit candidate vaccine of DENV-2 was prepared,which provides a refer-ence for the prevention of dengue virus.

The incidence rate of drug-induced liver injury （DILI） is increasing year by year with unknown mechanisms， and the treatment methods for DILI mainly include drugs， liver support systems， and liver transplantation， all of which have certain limitations. Therefore， the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation， promoting hepatocyte proliferation and regeneration， inhibiting the apoptosis of hepatocytes， improving oxidative stress， and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI， so as to provide a reference for further research.