Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

Objective To investigate the therapeutic effects and mechanisms of Maxing Shigan Decoction on cough variant asthma(CVA)rats.Methods Sixty rats were randomly divided into normal group,model group,low and high dose groups of Maxing Shigan Decoction,and high-dose of Maxing Shigan Decoction + signal transducer and activator of transcription 3(STAT3)activator Colivelin(Col)group,12 rats in each group.Except for the normal group,the CVA model was constructed by intraperitoneal injection of ovalbumin combined with moxa fumigation in all other groups of rats.After the corresponding treatment,the rats were observed for signs and cough counts,airway resistance(RE)was detected by pulmonary function meter,eosinophils(EOS)were counted by Diff-Quik staining,histopathological features of the lungs and bronchial tubes were observed by hematoxylin-eosin(HE)staining method,and the lung tissues were detected by enzyme-linked immunosorbent assay(ELISA)for monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α),and the protein expression levels of interleukin 6(IL-6),STAT3,and transient receptor potential vanilloid-1 channel(TRPV1)were detected by Western Blot.Results Compared with the normal group,rats in the model group showed obvious asthma symptoms,severe inflammatory cell infiltration was seen in the lung tissue,bronchial epithelial cell necrosis,ciliated adhesion,mucus,and RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,TRPV1 were elevated(P＜0.05);compared with the model group,rats in the low-and high-dose groups of Maxing Shigan Decoction showed significant improvement in asthma symptoms,reduction in lung and bronchial injury,and dose-dependent reduction in RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P＜0.05);compared with the high-dose group of Maxing Shigan Decoction,the rats in the high-dose Maxing Shigan Decoction+Col group showed increased asthma,increased lung and bronchial injury,and increased RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P＜0.05).Conclusion Maxing Shigan Decoction can effectively improve cough variant asthma in rats,and its mechanism is related to the inhibition of IL-6/STAT3 signaling pathway and the high expression of TRPV1.

Background The course of schizophrenia is prolonged,and patients have impaired social function and significantly reduced quality of life.Drug therapy combined with psychological therapy is particularly important for improving the quality of life of patients.Brief cognitive behavioral therapy(BCBT)has been widely applied in clinical practice,but current research on BCBT focuses more on improving patients' symptoms and lacks relevant reports on improving quality of life.Objective To evaluate the efficacy and influencing factors of BCBT combined with conventional treatment on improving the quality of life in patients with schizophrenia.Methods A total of 210 patients who met the diagnostic criteria for schizophrenia in the International Classification of Diseases(10th edition)(ICD-10)and were followed up at the outpatient department of Beijing Anding Hospital Capital Medical University from August 2011 to December 2016 were selected.Using a random number table method,patients were divided into study group and control group,with 105 cases in each group.Both groups received routine treatment,and the research group received a total of 8 BCBT sessions for 12 weeks on this basis.At the baseline period and 12 weeks of treatment,26 weeks of follow-up and 52 weeks of follow-up,Positive and Negative Syndrome Scale(PANSS),Personal and Social Performance Scale(PSP)and World Health Organization Quality of Life Brief(WHOQOL-BREF)were used for evaluation.Results The results of repeated measures analysis of variance showed that the time point effect and interaction effect of PANSS total score were statistically significant(F=118.783,8.083,P<0.01).The time point effect,inter group effect and interaction effect of PSP total score were statistically significant(F=94.358,4.048,5.490,P<0.05 or 0.01).The time point effect,inter group effect and interaction effect of the total score of WHOQOL-BREF were all statistically significant(F=12.330,4.168,4.142,P<0.05 or 0.01)Binary Logistic regression analysis showed that the study group(OR=1.861,95%CI:1.004～3.448)and young age(OR=1.044,95%CI:1.001～1.088)were protective factors for improving quality of life of patients,while high PANSS baseline score(OR=0.972,95%CI:0.945～0.999)was a risk factor for improving quality of life of patients.Conclusion The combination of BCBT and conventional treatment has an earlier onset of improvement in the quality of life of patients with schizophrenia,and long-term efficacy is superior to conventional treatment.

Objective To evaluate the factors affecting urinary stone detection rate using virtual unenhanced(VUE)images obtained from triphasic dual-energy CT urography(DECTU)based on Logistic regression analysis.Methods For this study,150 patients who had suspected urinary stone and underwent triphasic DECTU were included.The true unenhanced(TUE)images were reconstructed as 120 kVp-like images,and VUE images at the portal venous phase[VUE(VP)]and excretory phase[VUE(EP)]were obtained using iodine removal technique from portal venous and excretory phase DECTU images,respectively.Two readers independently evaluated the above three types of images,and recorded the number of urinary stones,their anatomical locations,and whether there was residual iodine on the VUE images.Stone size and CT number were recorded only on the TUE images.Stone size,CT number,anatomical location,and iodine contrast agent were included in univariate and multivariate Logistic regression analyses to evaluate the factors affecting urinary stone detection rate using VUE images.Thresholds for detecting urinary stones on VUE images were determined using receiver operating characteristics(ROC)analysis.Results We detected 304 stones on TUE images,while the detection rates were 92.4％and 71.4％when using VUE(VP)and VUE(EP)images,respectively.Stone size and CT number were important factors influencing urinary stone detection rate using VUE(VP)and VUE(EP)images(P＜0.01).The area under curve(AUC)of using stone size and CT number for detecting stones using the VUE(VP)images was up to 0.96,and as threshold values,stones with size larger than 3.52 mm and CT number greater than 469 HU were found to have high accuracy.However,the AUC decreased to 0.88 when we combined stone size,CT number and anatomical location using the VUE(EP)images.In addition,different contrast agents did not affect the detection rate of stones on the VUE(EP)images(P=0.57).The stone detection rate in the kidney was significantly lower than those on the VUE(EP)images(P＜0.001).Conclusion VUE(VP)images provide better stone detection.Stone size and CT number have significant impacts on the stone detection rate using VUE images.The lower stone detection rate in the kidney on the VUE(EP)images is related to the residual iodine.

Objective To evaluate the pharmacokinetics and safety of dapoxetine hydrochloride tablets in healthy Chinese subjects,and to assess the impact of food on dapoxetine pharmacokinetics.Methods A single-center,open-lable,two-period,randomized parallel study was conducted.A total of 22 healthy adult male subjects were enrolled and administered a single 30 mg oral dose of dapoxetine hydrochloride tablets,both under fasting and fed condition.Venous blood samples were collected at different time points,and dapoxetine concentrations in human plasma were measured using liquid chromatography tandem mass spectrometry(LC-MS/MS).Pharmacokinetic parameters were calculated using Phoenix WinNonlin 6.3 software,and statistical analysis was conducted with SPSS 19.0 software.Results The main pharmacokinetic parameters after oral administration of dapoxetine hydrochloride tablets in fasting and fed were as follows:Cmax were(230.71±88.91)and(216.27±58.32)ng·mL-1;AUC0-t were(1 054.99±442.11)and(1 292.56±534.49)ng·h·mL-1;AUC0-∞ were(1 175.03±510.58)and(1 447.42±656.25)ng·h·mL-1;tmax were(1.23±0.59)and(2.40±0.90)h;t1/2 were(15.95±6.13)and(16.21±6.34)h.Comparisons between the fasting and fed states,showed statistically significant differences in AUC0-t,AUC0-∞ and tmax(all P＜0.05),but not in Cmax and t1/2(all P＞0.05).The incidence of adverse events was 31.82％in the fasting state and 22.73％in the fed state,with no significant difference(P＞0.05).Conclusion Dapoxetine hydrochloride tablets were rapidly absorbed and eliminated in both fasting and fed states,with good safety;food slowed the absorption rate of dapoxetine and increaseed its overall exposure.

Objective:To investigate the correlation between immune function and age-related pulmonary fibrosis, as well as the potential impact of bacterial lysates on this condition.Methods:Twenty-four healthy male C57BL/6 mice, aged 24, were randomly divided into three groups: a control group(Group N), a pulmonary fibrosis group(Group M), and a pulmonary fibrosis+ bacterial lysis product intervention group(Group P). Mice in Groups M and P were intratracheally injected with bleomycin(5 mg/kg)to induce a mouse pulmonary fibrosis model, while mice in Group N were injected with saline.After modeling, mice in Group P were orally administered 0.4 ml of a bacterial lysis product once a day.After 28 days, lung tissue and blood samples were collected for analysis.Pathological changes in lung tissue were assessed using hematoxylin and tosin staining(HE)and Masson staining and the Ashcroft score.The expression of CD4+ and CD8+ in lung tissue was evaluated using immunohistochemistry.The levels of serum interferon-γ(INF-γ), interleukin-3(IL-13), and immunoglobulin A(IgA)protein were measured using Enzyme-linked Immuno Sorbent Assay(ELISA). The levels of INF-γ and IL-13 mRNA in lung tissue were determined using Real-Time Quantitative Transcription PCR(RT-qPCR). Additionally, the protein expression levels of matrix metalloprotein-9(MMP-9)and tissue inhibitor of metalloproteincise 1(TIMP-1)in lung tissue were assessed using blot analysis.Results:The degree of lung fibrosis was significantly reduced in mice in group P compared with group M when treated with bacterial lysis products.Group M showed a significant decrease in the expression of CD4+ T cells and an increase in the expression of CD8+ T cells( P<0.05)compared to group N. Additionally, the content of IgA was decreased( P<0.05)in group M. On the other hand, group P showed a significant increase in the expression of CD4+ T cells and a decrease in the expression of CD8+ T cells( P<0.05)compared to group M. Furthermore, the content of IgA was elevated( P<0.05)in group P. After bacterial lysis product intervention, mRNA and protein expression levels of IFN-γ were elevated( P<0.05), while mRNA and protein expression levels of IL-13 were reduced( P<0.05). Moreover, protein expression of MMP-9 and TIMP-1 was significantly up-regulated in group M compared with group N( P<0.05), and decreased after bacterial lysis product intervention( P<0.05). Conclusions:It is well-known that immune mechanisms play a crucial role in the development of pulmonary fibrosis.The use of bacterial lysates has been found to effectively regulate immune balance and mitigate the severity of pulmonary fibrosis in elderly mice.

Objective As primary Sj?gren's syndrome(pSS)primarily affects the salivary glands,saliva can serve as an indicator of the glands'pathophysiology and the disease's status.This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis. Methods The discovery set contained 49 samples(24 from pSS and 25 from age-and gender-matched healthy controls[HCs])and the validation set included 25 samples(12 from pSS and 13 from HCs).Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio.Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition(DIA)strategy on a 2D LC-HRMS/MS platform to reveal differential proteins.The crucial proteins were verified using DIA analysis and annotated using gene ontology(GO)and International Pharmaceutical Abstracts(IPA)analysis.A prediction model for SS was established using random forests. Results A total of 1,963 proteins were discovered,and 136 proteins exhibited differential representation in pSS patients.The bioinformatic research indicated that these proteins were primarily linked to immunological functions,metabolism,and inflammation.A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm,and was validated as the predictive biomarkers exhibiting good performance with area under the curve(AUC)of 0.817 for discovery set and 0.882 for validation set. Conclusions The candidate protein panel discovered may aid in pSS diagnosis.Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients.DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.

Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.

Objective To explore the differences in scapular motion and shoulder function between patients suffering from rotator cuff tears(RCT)with and without type Ⅲ scapular dyskinesis(SD).Meth-ods Between September 2021 and March 2023,sixteen patients suffering from rotator cuff tears with SD(SD group)and 17 counterparts without SD(non-SD group)were recruited from the Sports Hospital of the General Administration of Sport of China.Their scapular motion was assessed by measuring three parameters in the X-rays,including scapular spine line(LSS),scapular upward rotation angle(SU-RA),and coracoid upward shift distance(CUSD).Moreover,their shoulder range of motion in flexion,abduction and external rotation were recorded,and further evaluated using the Pain Visual Analog Scale(VAS)and American Shoulder and Elbow Surgeons Score(ASES).Results No significant differenc-es were found between the two groups in the average score of SURA,CUSD and LSS at 0°～30° shoul-der abduction,or in that of CUSD and LSS at 60°～90°shoulder abduction.However,the average SU-RA score of the SD group at 60°～90°shoulder abduction was significantly greater than the other group(P<0.05).The shoulder ranges of motion during active flexion,abduction and external rotation were significantly smaller in the SD group than in the non-SD group(P<0.05).Moreover,the average VAS score in the SD group was significantly higher than the non-SD group(P<0.05),while the average ASES score was significantly lower than the latter group(P<0.05).Conclusions RCT patients type III SD exhibits greater scapular upward rotation during shoulder abduction compared to those without SD.Moreover,the former patients suffer from more severe pain and have worse shoulder range of motion and functional performance than the latter.