ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

ObjectiveTo explore the mechanism of Sangpi Zhike prescription in treating cough after respiratory syncytial virus （RSV） infection through the "lung-intestine co-treatment" approach using network pharmacology and animal experimental validation. MethodsActive ingredients and targets of Sangpi Zhike prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology （TCMSP） database. Disease targets were obtained from GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. Protein-protein interaction （PPI） networks and drug-component-target networks were constructed using overlapping targets between drugs and diseases to identify core targets. Gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analyses were performed on the overlapping targets. Sixty mouse models were established： 10 as the normal group， and the remaining mice were infected with RSV via slow nasal drip of RSV suspension， with cough induced using capsaicin solution. After modeling， mice were divided into a model group， a Montelukast Sodium group （1 mg·kg^-1·d^-1）， and low， medium， and high dose groups of Sangpi Zhike prescription （4.875，9.75，and 19.5 g·kg^-1·d^-1）， with 10 mice per group. From day 14 after RSV infection， the normal and model groups received saline via gavage， while other groups received corresponding drug treatments once daily for 5 d. Hematoxylin-eosin（HE） staining was used to observe pathological changes in lung and intestinal tissue. The protein content of extracellular signal-regulated kinase 1/2 （ERK1/2） and phosphorylated （p）-ERK1/2 in the lung and colon tissue of mice was detected by Western blot. Real-time polymerase chain reaction（Real-time PCR） detected ERK1/2 mRNA expression in lung and intestinal tissue. Immunohistochemistry assessed p-MEK1/2， p-ERK1/2， p-c-Fos protein levels， and inflammatory cytokines interleukin（IL）-4 and （TNF）-α in lung and colon tissue. ResultsNetwork pharmacology identified 184 active ingredients and 684 targets in Sangpi Zhike prescription， with 1 344 RSV-related disease targets and 209 overlapping targets. Core targets included TNF， Fos， and Jun. KEGG enrichment revealed 179 pathways， primarily mitogen-activated protein kinase（MAPK）， cancer， TNF， and IL-17 signaling pathways. Animal experiments showed that， compared to those of the normal group， the lung tissue sections of the model group showed typical inflammatory damage， infiltration of inflammatory cells， rupture of alveolar septa， extensive alveolar fusion， and disruption of tight junctions between single-layer columnar epithelial cells in the intestinal tissue. The values of p-ERK1/2 and ERK1/2 in lung and intestinal tissue were significantly increased （P<0.01）， and the expression level of ERK1/2 mRNA was significantly elevated （P<0.01）. The levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α along the ERK pathway were significantly increased （P<0.05， P<0.01）. Compared to the model group， Sangpi Zhike prescription groups showed reduced lung and intestinal inflammation， decreased p-ERK1/2/ERK1/2 ratios （P<0.05，P<0.01）， lower ERK1/2 mRNA levels， and downregulated ERK pathway proteins （P<0.05，P<0.01）. ConclusionSangpi Zhike prescription alleviates cough and intestinal symptoms after RSV infection via the "lung-intestine co-treatment" mechanism by suppressing expression levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α on ERK pathway components， thereby mitigating lung and intestinal pathological damage.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

ObjectiveTo explore the mechanism by which Qijia Rougan decoction ameliorates liver fibrosis through amino acid/fatty acid metabolic reprogramming and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway， based on the miRNA-mRNA regulatory network and the interaction between metabolism and signaling pathways. MethodsSprague-Dawley （SD） rats were randomized into four groups （n=8）： control， model， and low-dose and high-dose （7.0， 28.0 g·kg^-1·d^-1， respectively） Qijia Rougan decoction. Liver fibrosis was induced by subcutaneous injection of carbon tetrachloride （CCl₄）. From week 9， drug intervention was implemented for 7 weeks. After the final administration， the pathological changes in the liver were evaluated through hematoxylin-eosin （HE） and picrosirius red （PSR） staining. An automated biochemical analyzer was used to measure the serum levels of biochemical indicators， including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， total bile acid （TBA）， albumin （ALB）， and cholesterol （TC）. High-throughput miRNA sequencing was performed to identify differentially expressed miRNAs （DemiRs） during liver fibrosis. A miRNA-mRNA interaction network was constructed to identify key targets， which were then subjected to GO and KEGG enrichment analyses. The expression levels of selected DemiRs were validated by Real-time PCR. ResultsCompared with the control group， the model group showed marked hepatic lobular necrosis， increased collagen deposition， significant fibrosis， elevated serum levels of ALT， AST， ALP， and TBA （P<0.01）， and declined levels of ALB and TC （P<0.01）. Compared with the model group， Qijia Rougan decoction treatment reduced hepatic necrosis， collagen accumulation， and fibrosis， lowered the serum levels of ALT， AST， ALP， and TBA （P<0.01）， and raised the levels of ALB and TC （P<0.01）. Integrated miRNA-seq and RNA-seq analysis identified 31 DemiRs （6 upregulated and 25 downregulated） and 498 targets. The expression trends of four selected DemiRs， including rno-miRNA-376b-3p， were consistent with sequencing results （R²=0.93）. Functional annotation revealed that top 20 upregulated targets were enriched in amino acid and fatty acid metabolism， while top 20 downregulated targets were significantly associated with the PI3K/Akt signaling pathway and cancer progression. ConclusionQijia Rougan decoction alleviates liver fibrosis by reconstructing the miRNA-mRNA regulatory network， promoting metabolic reprogramming， and inhibiting the PI3K/Akt signaling pathway. These findings provide mechanism evidence supporting the multi-targeted antifibrotic effects of traditional Chinese medicine compound formulas.

Curzerene, a sesquiterpene compound isolated from Curcuma Radix, exhibits various therapeutic effects, such as anti-tumor and anti-hyperlipidemic properties. However, its neuroprotective effects have not yet been reported. This study focused on exploring the neuroprotective effect of curzerene and elucidating its potential mechanism by combining molecular biotechnology with multi-omics approaches. Curzerene was orally administered to LPS-induced depressive-like behaviors and cognitive impairment in mice for 14 days, and the related biochemical parameters were evaluated. The possible mechanisms were elucidated using qRT-PCR, Western Blot, immunofluorescence, untargeted metabolomics, GC-MS and 16S rDNA comprehensively. Curzerene ameliorated depression symptoms and cognitive impairment by increasing the preference for sucrose in SPT and the central area and total distance traveled in OFT, reducing the immobility time in TST and FST, as well as rising the spontaneous alternation ratio in Y maze. Multiple molecular biology techniques analyses indicated the ameliorative effect of curzerene via HMGB1/RAGE/ TLR4 pathway. Moreover, curzerene primarily regulates purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, pyrimidine metabolism, etc. Furthermore, intervention increased the relative abundance of Parabacteroides, Clostridia_UCG-014_unclassified, and Rhodospirillales_unclassified, and enhanced the production of SCFAs. This work demonstrated that curzerene effectively protects against LPS-induced neurological damage, potentially by inhibiting the HMGB1/ RAGE/TLR4 pathway through the restoration of gut microbiota homeostasis, modulation of metabolites, and enhancement of SCFAs. In conclusion, this study offers new perspectives on the therapeutic possibilities of curzerene in mitigating depressive-like behaviors and cognitive impairment.

ObjectiveTo explore the clinical efficacy of Juanbitang hot compress pack combined with intensive rehabilitation training in stroke patients with hemiplegia. MethodsA total of 80 stroke patients with hemiplegia were selected and assigned into a control group （40 cases） and an observation group （40 cases） according to the random number table method. The control group received conventional rehabilitation training and nursing intervention，while the observation group was additionally treated with Juanbitang hot compress pack. The two groups were compared in terms of the neurological function （national institute of health stroke scale score，NIHSS score），muscle strength，motor function （fugl-meyer assessment scale score，FMA score），daily living activity （modified barthel index，MBI），balance ability （berg balance scale score，BBS score），trunk control ability （Sheikh Trunk Control Test score，Sheikh TCT score），and homocysteine （Hcy） level before and after treatment. ResultsAfter treatment，the observation group had lower NIHSS score and Hcy level than the control group （P<0.05）. The total response rate of the observation group （97.50%） was higher than that of the control group （77.50%）. The scores of upper limb and lower limb FMA，MBI，BBS，and Sheikh TCT in the observation group were all higher than those in the control group （P<0.05）. ConclusionThe application of Juanbitang hot compress pack combined with rehabilitation training can effectively improve the neurological function，muscle strength，motor function，daily living ability，balance ability，and trunk control ability and reduce the Hcy level in stroke patients with hemiplegia，demonstrating enhanced clinical efficacy.

ObjectiveTo investigate the relationship between TypeⅠHelicobacter pylori （H. pylori） infection and the risk of colorectal neoplasms （CRN） in patients attending gastroenterology clinics， and to evaluate its predictive value for CRN in this population. MethodsWe included 2 148 patients presenting to the Department of Gastroenterology， with 677 assigned to the CRN group and 1 471 to the non-CRN group.H.pylori antibody typing was performed using Western blot， with typeⅠdefined as positivity for CagA and/or VacA antibodies， and type II as positivity only for UreA/B antibodies. Statistical analyses included univariate screening， multivariate logistic regression， and receiver operating characteristic （ROC） curve evaluation. ResultsTypeⅠH.pylori seropositivity was significantly more prevalent in the CRN group than in the non-CRN group （54.51% vs 45.62%， P_adjust<0.05）. No significant differences were observed for type Ⅱ H.pylorior seronegative subjects. The CRN group had higher proportions of males， hypertension， diabetes， smoking， and alcohol use， as well as elevated body mass index， fasting plasma glucose， triglycerides， and uric acid， along with lower high-density lipoprotein levels （all P<0.05）. Multivariate analysis confirmed typeⅠH.pylori （OR=1.303）， alcohol consumption （OR=2.315）， male （OR=1.592）， and age （OR=1.048） as independent risk factors for CRN. Although type I H.pylori alone showed limited predictive value （AUC=0.544）， a combined model incorporating alcohol use， age， and sex demonstrated significantly improved discriminative ability （AUC=0.681， sensitivity 59.1%， specificity 68.2%）. ConclusionTypeⅠH. pylori infection predicts the risk of CRN in gastroenterology patients. Assessing it can help to optimize the identification of high-risk individuals and inform targeted screening strategies.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

The C 2-C 7 sagittal vertical axis (SVA) is an essential biomechanical parameter for evaluating cervical spine alignment, and it is integral to the pathogenesis, progression, and prognosis of cervical spine disorders. This parameter is widely used in evaluating cervical sagittal balance and functional status. Internationally, a C 2-C 7 SVA of less than 25 mm is considered within the cervical range for sagittal balance, while values exceeding 40 mm indicate cervical sagittal imbalance or deformity. An increased C 2-C 7 SVA disrupts cervical spine biomechanics, leading to heightened static and dynamic loads on the cervical musculature. This, in turn, results in muscle fatigue and discomfort. In the short term, patients may experience axial neck symptoms, while a sustained elevation in SVA over time significantly raises the risk of cervical disc degeneration, radiculopathy, and myelopathy. Additionally, a higher C 2-C 7 SVA postoperatively places excessive stress on adjacent spinal segments, which can accelerate degeneration of intervertebral discs and facet joints, contributing to adjacent segment degeneration. Both short-term and long-term postoperative evaluations have shown that an increase in C 2-C 7 SVA is typically associated with poorer surgical outcomes, whereas effective control of SVA values is closely linked to better functional recovery. Therefore, in clinical practice, maintaining C 2-C 7 SVA within the normal range (<25 mm) is critical not only for optimizing treatment results but also for significantly reducing postoperative complications and improving overall patient quality of life.

AIM:This study aims to design pH/near-infrared(NIR)dual-responsive metal-organic framework composite nanoparticles co-loaded with indocyanine green(ICG)and sphingosine kinase 1(SphK1)siRNA(siSphK1),and to evaluate their anticancer efficacy against non-small-cell lung cancer A549 cells.METHODS:The ZIF-8 nanopar-ticles were synthesized and loaded with ICG and siSphK1 to prepare ZIF-8@ICG@siSphK1 nanoparticles.Their morpholo-gy,particle size,surface charge,and crystalline structure were characterized through transmission electron microscopy,dynamic light scattering,and X-ray diffraction.Stability,siSphK1 encapsulation and protection,and pH/NIR response were assessed.The gene silencing efficacy and anticancer activity in A549 cells were evaluated using Western blot,RT-qPCR,MTT assay,flow cytometry,and reactive oxygen species(ROS)fluorescence staining.RESULTS:The ZIF-8@ICG@siSphK1 nanoparticles exhibited a typical polyhedral structure with an average particle size of(76.8±0.9)nm and a ζ potential of(9.2±0.1)mV.The nanoparticles effectively encapsulated siSphK1,protecting it from RNase degra-dation,and demonstrated excellent NIR responsiveness with a photothermal conversion efficiency of 39.7%.After 10 h of 808 nm laser irradiation,siRNA cumulative release was significantly higher at pH 5.5 compared with pH 7.4.In A549 cells,the nanoparticles efficiently delivered siSphK1 under NIR irradiation,significantly down-regulated SphK1 gene ex-pression,inhibited cell proliferation,induced apoptosis,and increased intracellular ROS levels.CONCLUSION:The ZIF-8@ICG@siSphK1 nanoparticles effectively induce cytotoxic effects against A549 cells through gene silencing and pho-tothermal therapy.