OBJECTIVE To compare the efficacy and safety of dupilumab versus thalidomide in the treatment of refractory prurigo nodularis （PN） in adults. METHODS A retrospective analysis was conducted on the clinical data of 123 adult patients with refractory PN admitted to Wuhan First Hospital from May 2021 to June 2024. Among them， 63 patients who received dupilumab comprised the observation group and 60 patients who received thalidomide comprised the control group. Clinical efficacy indicators [Investigator Global Assessment （IGA） score， Pruritus Numerical Rating Scale （P-NRS） score， Patient-Oriented Eczema Measure （POEM） score， and Dermatology Life Quality Index （DLQI） score]， allergic biomarkers [eosinophil （EOS） count in peripheral blood and serum total immunoglobulin E （IgE） level]， psychological scores [Hospital Anxiety and Depression Scale （HADS）] before and after treatment， as well as the occurrence of adverse drug reaction during treatment， were compared between the two groups. RESULTS Before treatment， there were no statistically significant differences between the two groups in above clinical efficacy indicators， allergic biomarkers， or psychological scores （P＞0.05）. At 4， 8， 12 and 16 weeks after treatment， both groups showed significant decreases in IGA score （except for the control group 4 weeks after treatment）， IGA activity score （except for the control group 4 weeks after treatment）， P-NRS score， POEM score， DLQI score （except for the control group 4 weeks after treatment）， serum EOS count， and serum total IgE level compared with baseline （P＜0.05）； at 12 and 16 weeks after treatment， scores on both the HADS-anxiety subscale and HADS-depression subscale were also significantly lower than baseline in both groups （P＜0.05）； the observation group was significantly lower than the control group （P＜0.05）. The overall incidence of adverse events was 12.70% in the observation group， which was significantly lower than 28.33% in the control group （P＜0.05）. CONCLUSIONS Dupilumab treatment in adults with refractory PN demonstrates superior efficacy compared with thalidomide in improving skin lesions， relieving pruritus， reducing peripheral EOS counts and serum total IgE， and improving quality of life and psychological status， while showing a more favorable safety profile.

This study was performed to investigate the prognostic value of JCHAIN gene in the distant metastasis(DM)of breast cancer(BC)and its possible regulatory mechanism through bioinformatics analysis.TCGA database BC transcriptome sequencing data were grouped according to sample source,and LIMMA was used to identify differentially expressed genes(DEGs),and combined with clinical data,genes related to tumorigenesis and metastasis were further screened.Single-factor Cox analysis revealed that 10 key genes were significantly associated with OS,while multi-factor Cox analysis further filtered out 4 genes with significant correlation.The analysis algorithm of 8 immune infiltration cell subtypes were used to evaluate the correlation of JCHAIN expression level with the subtype of infiltrating cells and the proportion of each cellular component in the tumor microenvironment.the genome-wide drug sensitivity of anti-cancer drugs(GDSC)database was used to analyze the chemotherapy drug sensitivity of BC patients with different JCHAIN expression levels;dual-luciferase reporter system was used to explore the mechanism of low JCHAIN expression in BC with DM.Based on the screened key genes,a prognostic model was successfully constructed,and it was found that with the increase of model risk value,the gene expression of JCHAIN and TUBA3D showed a down-regulation trend,while the gene expression of SPDYC and CRISP3 was up-regulated.②The expression of gene JCHAIN in BC patients with DM was lower than those in patients without DM and normal controls.In clinical outcomes,the expression level of gene JCHAIN in the death group was lower than that in the survival group,and with the progression of the disease(stage)or the deepening of malignancy,the expression of gene JCHAIN basically showed a downward trend.The number of immune cells in the JCHAIN high expression group was generally higher than that in the low expression group.For example,among the six algorithms that predict the expression of B cells and T cells(CD4+/CD8+),the JCHAIN high expression group is higher than the low expression group.Based on the GDSC database,the JCHAIN expression level could predict the chemotherapeutic drug sensitivity,and the expression level is positively correlated with the drug sensitivity.The luciferase detection value of the experimental group with the participation of the recombinant plasmid of transcription factor TWIST1(TW)was lower than that of the control group without the participation of the TW recombinant plasmid.Taken together,JCHAIN and TUBA3D are protective factor against risk for BC,while SPDYC and CRISP3 are risk factor;lower JCHAIN level may promote the occurrence and DM of BC,while higher JCHAIN level may promote the infiltration of various immune cells.Furthermore,BC patients with high expression of JCHAIN may have higher sensitivity to therapeutic drugs than those with low expression.The transcription factor TW can bind to the JCHAIN promoter sequence and perform negative regulation.

Objective To explore the optimal ratio of Baitong decoction based on efficacy,clarify its spectrum-effect relationship,and identify its potential quality markers.Methods An ulcerative colitis(UC)model in mice was established using dextran sulfate sodium.The efficacy of Baitong decoction with varying drug ratios was assessed by evaluating the apparent score,pathological score and inflammatory factor changes of UC in each group of experimental animals.The fingerprints of Baitong decoction with different ratios were established by high performance liquid chromatography(HPLC),and the relationship between the content of each substance and its efficacy was analyzed by partial least squares regression to determine the potential quality markers of Baitong decoction.Results Baitong decoction was most effective in relieving ulcerative colitis when the mass ratio of Fuzi,Ganjiang and Congbai was 1∶2∶2.The fingerprinting identified 14 common peaks across 7 ratios,with 9 peaks were found to be associated with the remission of ulcerative colitis by partial least squares regression analysis.Conclusion The optimal ratio of Fuzi,Ganjiang and Congbai for treating UC is 1∶2∶2.The spectrum-effect relationship analysis suggested that the quality markers of Baitong decoction may be the substances represented by peak 2(benzoylaconine),3,5,6,8(mesaconine),9(aconitine),10(hypaconitine),13(10-gingerol)and 14.

Objective:To explore potential biomarkers that can predict the clinical efficacy of PD-1/PD-L1 inhibitors in malig-nancies.Methods:The PubMed,Web of Science,CNKI,Wanfang and VIP databases were searched from the establishment of the database to September 20,2022.After literature screening,data extraction and the risk of bias were evaluated independently by two evaluators,the Meta-analysis was performed using RevMan5.4 and STATA16.0 software.Results:This paper included 18 studies with a total of 4 018 patients.Tumor patients with a high tumor mutational burden(TMB)were found to have higher overall survival(OS)(P=0.003,P=0.01)and progression-free survival(PFS)(P=0.000 2,P=0.04)with PD-1/PD-L1 inhibitors within 1 year and 2 years of follow-up.At different follow-up times,with 1%as the critical value,there was no statistical significance in the level of PD-L1 ex-pression as a biomarker for predicting OS and PFS of PD-1/PD-L1 inhibitors(P>0.05).Conclusion:TMB can be used as a biological indicator to predict the clinical efficacy of PD-1/PD-L1 inhibitors in patients with malignant tumors within 2 years after treatment,but whether its efficacy can last longer remains to be further studied.PD-L1 single test is not currently a biomarker for predicting the bene-fit of PD-1/PD-L1 inhibitors.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To understand the epidemiology of rubella and the genetic characteristics of the virus circulating during the period 2021-2022, providing basic scientific data for rubella prevention and control in China.Methods:National rubella incidence data for the period 2021-2022 were obtained from the Infectious Disease Surveillance System module and the Surveillance Report Management module of the China′s Disease Prevention and Control Information System. Positive rubella virus(RuV)isolates were obtained from the National Measles/Rubella Laboratory Network. Two nucleotide (nt) fragments [F1-480 (8 633-9 112 nt) and F2-633 (8 945-9 577 nt)] located in the E1 gene were amplified and determined by reverse transcription polymerase chain reaction (RT-PCR), and the target gene (E1-739) was obtained after collating and splicing. The sequences obtained in this study were used to construct a phylogenetic tree with the reported reference strains for genotype and lineage identification. Additionally, the phylogenetic analysis was performed to assess their genetic relatedness of RuV strains prevalent in China during 2018-2020 from GenBank database.Results:In 2021-2022, the rubella incidence in China was 0.06/100, 000 (2021: 840 cases; 2022: 784 cases), with cases primarily concentrated in the western and southern provinces. Age distribution analysis showed that rubella cases in 2021-2022 was mainly in children under 5 years of age (2021: 34.17%, 287/840; 2022: 42.09%, 330/784), with the highest proportion in children aged 0-2 years. Further analysis of the immunization history of cases revealed that in the 8-23 months age group, a significant proportion of cases had received only one dose of rubella containing vaccine (RCV); cases in the 2-14 years age group were mainly among children who had received two or more doses of RCV; however, cases over 15 years of age were primarily found in individuals who had not received RCV or had unknown immunization history. National virological surveillance data showed that totally 22 RuV virus isolates were obtained, from 6 provinces in China during 2021-2022, which belonged to lineage 1E-L2 (11 strains) and 2B-L2c (11 strains). And these viruses displayed high genetic homology with RuV prevalent from 2018 to 2020.Conclusions:The incidence of rubella in China was maintained at a low level during 2021-2022, and the prevalent RuV strains were lineage 1E-L2 and 2B-L2c.

OBJECTIVE To investigate the effects and mechanism of Yiqi huoxue decoction （YQHX） on lumbar disc herniation in rats. METHODS Rats were randomly divided into sham operation group， model group， NF-κB inhibitor group （QNZ group， 1 mg/kg）， YQHX group （9.1 g/kg） and combination group （YQHX+QNZ group， the same dose as each single drug group）， with 10 rats in each group. Except for sham operation group， lumbar disc herniation model of rats was induced in other groups； administration groups were given QNZ intraperitoneally or/and YQHX intragastrically， once a day， for 8 consecutive weeks. The severity of intervertebral disc herniation was evaluated in each group； the pathological changes of intervertebral discs and the changes of autophagy of nucleus pulposus cells were all observed； the level of tumor necrosis factor-α （TNF-α） in serum， and the ratios of Bcl-2/adenovirus E1B interacting protein 3 （BNIP3） and Beclin-1 positive cells in intervertebral disctissues were detected； the phosphorylation of nuclear factor-κB （NF-κB） p65， the expressions of tumor necrosis factor receptor- associated factor-2 （TRAF-2）， TRAF-3， BNIP3 and LC3B protein， and mRNA expressions of NF-κB p65， LC3B， p62，BNIP3 and Beclin-1 were determined. RESULTS Compared with model group， Pfirrmann grading score decreased significantly，the pathological injury of intervertebral disc tissue was relieved in YQHX group； the number of autophagosomes in nucleus pulposus cells increased； serum level of TNF-α and mRNA expression of p62 in intervertebral disc tissue decreased significantly； the ratios of BNIP3 and Beclin-1 positive cells， the phosphorylation of NF-κB p65， the expressions of TRAF-2， TRAF-3， BNIP3 and LC3B protein as well as the mRNA expressions of NF- κB p65， LC3B， BNIP3 and Beclin-1 decreased significantly in intervertebral disc tissues （P＜0.05）. The changes of above indexes in YQHX group were reversed partly in YQHX+QNZ group. CONCLUSIONS YQHX promotes the elevation of autophagy level of intervertebral discs， slows down the inflammatory response and the progression of lumbar disc herniation by activating the NF-κB signaling pathway.

[摘 要] 目的：系统评估经动脉化疗栓塞（TACE）和酪氨酸激酶抑制剂（TKI）联合（TT）联合或不联合PD-1抗体（PD-1Ab）治疗晚期肝细胞癌（aHCC）的疗效与潜在不良反应（AE）。方法：检索PubMed、中国知网（CNKI）、Embase、Web of Science等数据库，时限为各数据库建库始至2024年1月31日。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后，采用Stata16.0软件进行Meta分析。结果：纳入17项研究，共2 334例aHCC患者。Meta分析结果显示，与TT疗法相比，PD-1Ab的加入能显著改善aHCC患者的总生存期（OS）[HR = 0.44，95% CI（0.36，0.51），P < 0.000 01]和无进展生存期（PFS）[HR = 0.47，95% CI（0.42，0.52），P < 0.000 01]，同时提高aHCC患者的客观缓解率（ORR）[HR = 1.65，95% CI（1.46，1.86），P < 0.000 01]和疾病控制率（DCR）[HR = 1.26，95% CI（1.15，1.38），P < 0.000 01]；不同基线资料如ECOG-PS、肝外转移与否、BCLC分期、肿瘤大小、Child-Pugh评分及肝门静脉侵犯与否等aHCC患者均可从TT PD-1Ab疗法中获益；两治疗方案间全级别与 ≥3级AE的总发生率无显著差异，但高血压、甲状腺功能减退及反应性皮肤血管增生等症状在接受TT PD-1Ab治疗的患者中更为常见。结论：相较于TT疗法，PD-1Ab的加入可显著延长aHCC患者OS和PFS，并提高其整体ORR与DCR；TT PD-1Ab治疗组患者发生全级别及≥ 3级AE的整体发生率没有显著增加，整体耐受性良好，但在高血压、皮肤与黏膜及甲状腺AE上有较高的发生率，应予以重视。

OBJECTIVE To study the structural characteristics of purified polysaccharide isolated from Polygonatum cyrtonema Hua and explore its anti-fatigue and intestinal bacteria improvement effects,so as to provide theoretical basis for the development of products using this polysaccharide as functional ingredients.METHODS PMP pre-column derivatization-high performance liquid chromatography,trimethylsilyl ether derivatization-gas chromatography and other methods were used to chemically characterize the pu-rified polysaccharide;the mouse weight-loading swimming test and biochemical indicators were used to evaluate its anti-fatigue effect;16S rRNA intestinal flora sequencing was adopted to study the effect of the purified product in improving intestinal bacteria.RESULTS The obtained polysaccharide was a fructan product and contained small amounts of glucose(Glc),galactose(Gal),arabinose(Ara),mannose(Man),rhamnose(Rha)and galacturonic acid(GalA),which had a relative molecular mass in the range of 0.4-285 kDa,and the molecular weight of the main component was around 3 kDa.Compared with the model group,the high-dose polysaccha-ride group could significantly prolong the exhaustive swimming time of mice(P＜0.01),reduce the levels of BUN and UA in serum and the LA(P＜0.01)and MDA levels(P＜0.05)in muscle tissue,and enhance SOD(P＜0.01),GSH-Px(P＜0.001)and CAT(P＜0.05)levels in liver tissue.Compared with the blank control group,the low-dose polysaccharide group could increase the relative a-bundance of probiotics Eggerthelaceae(g_unclassified_f_Eggerthelaceae)and Weissella(g_Weissella)in the fecal microorganisms of mice(P＜0.05).CONCLUSION The chemical composition of purified polysaccharide isolated from Polygonatum cyrtonema Hua is determined,and it is proven that the polysaccharide has a good anti-fatigue effect and can promote the growth of probiotics in the intes-tine,which provides a basis for product development using this polysaccharide as a functional ingredient.

This study was performed to investigate the prognostic value of JCHAIN gene in the distant metastasis(DM)of breast cancer(BC)and its possible regulatory mechanism through bioinformatics analysis.TCGA database BC transcriptome sequencing data were grouped according to sample source,and LIMMA was used to identify differentially expressed genes(DEGs),and combined with clinical data,genes related to tumorigenesis and metastasis were further screened.Single-factor Cox analysis revealed that 10 key genes were significantly associated with OS,while multi-factor Cox analysis further filtered out 4 genes with significant correlation.The analysis algorithm of 8 immune infiltration cell subtypes were used to evaluate the correlation of JCHAIN expression level with the subtype of infiltrating cells and the proportion of each cellular component in the tumor microenvironment.the genome-wide drug sensitivity of anti-cancer drugs(GDSC)database was used to analyze the chemotherapy drug sensitivity of BC patients with different JCHAIN expression levels;dual-luciferase reporter system was used to explore the mechanism of low JCHAIN expression in BC with DM.Based on the screened key genes,a prognostic model was successfully constructed,and it was found that with the increase of model risk value,the gene expression of JCHAIN and TUBA3D showed a down-regulation trend,while the gene expression of SPDYC and CRISP3 was up-regulated.②The expression of gene JCHAIN in BC patients with DM was lower than those in patients without DM and normal controls.In clinical outcomes,the expression level of gene JCHAIN in the death group was lower than that in the survival group,and with the progression of the disease(stage)or the deepening of malignancy,the expression of gene JCHAIN basically showed a downward trend.The number of immune cells in the JCHAIN high expression group was generally higher than that in the low expression group.For example,among the six algorithms that predict the expression of B cells and T cells(CD4+/CD8+),the JCHAIN high expression group is higher than the low expression group.Based on the GDSC database,the JCHAIN expression level could predict the chemotherapeutic drug sensitivity,and the expression level is positively correlated with the drug sensitivity.The luciferase detection value of the experimental group with the participation of the recombinant plasmid of transcription factor TWIST1(TW)was lower than that of the control group without the participation of the TW recombinant plasmid.Taken together,JCHAIN and TUBA3D are protective factor against risk for BC,while SPDYC and CRISP3 are risk factor;lower JCHAIN level may promote the occurrence and DM of BC,while higher JCHAIN level may promote the infiltration of various immune cells.Furthermore,BC patients with high expression of JCHAIN may have higher sensitivity to therapeutic drugs than those with low expression.The transcription factor TW can bind to the JCHAIN promoter sequence and perform negative regulation.