[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 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.

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.

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.

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.

Edible bird's nest (EBN) is a kind of natural invigorant with a long history of consumption in Asia, especially in China. EBN is formed by mixing the saliva of swiftlets (Aerodramus) with feathers and other components during the breeding season. Proteins are the most important nutrient in EBN. By studying proteins in EBN, we can not only elucidate their components at the molecular level, but also study their bioactivities. Therefore, it is of great significance to study the proteins in EBN. Previous research on the proteins in EBN was preliminary and cursory, and no one has summarized and analyzed the proteins in EBN and correlated the bioactivities of these proteins with the biological functions of EBN. This article focused on the proteins in EBN, listed the proteins identified in different proteomic studies, and introduced the sources, structures and bioactivities of the most frequently identified proteins, including acidic mammalian chitinase, lysyl oxidase homolog 3, mucin-5AC, ovoinhibitor, nucleobindin-2, calcium-binding protein (MW: 4.5 × 10⁴) and glucose-regulated protein (MW: 7.8 × 10⁴). The properties of these proteins are closely related to the bioactivities of EBN. Therefore, this article can provide inspiration for further research on the efficacy of EBN.

[摘 要] 目的：探讨PD-1/PD-L1通路及相关免疫细胞在宫颈鳞癌（cervical squamous cell cancer，CSCC）发生、发展中的变化特点及其临床意义。方法：收集2018年12月至2020年9月在福州市第一医院接受手术的CSCC患者和健康体检人员的癌组织/宫颈组织和外周血样本，分为健康对照组、宫颈上皮内癌变（cervical intraepithelial neoplasia，CIN）Ⅱ级组、CIN Ⅲ级组和CSCC组，代表CSCC发生、发展进程各阶段，每组50例。ELISA法检测各组人员的外周血血浆中PD-1、PD-L1、叉头状转录因子P3（FOXP3）的表达水平，FCM法检测各组人员外周血PD-1+CD4+CD25+CD127-/low细胞的数量，应用多色荧光组织染色法检测肿瘤浸润性淋巴细胞（TIL）在CSCC组织中的分布特点。结果：随着模拟的CSCC发生和发展，外周血中PD-1、PD-L1和FOXP3 的表达呈上升趋势，术后则呈下降趋势。在CSCC患者抗凝全血中，CD4+、CD4+CD25+CD127-/low以及PD-1+CD4+CD25+CD127-/low细胞占淋巴细胞的比例增加。在CSCC组织中可见大量CD4+、CD8+和FOXP3+细胞浸润，其中CD4+和FOXP3+细胞主要围绕肿瘤细胞聚集区分布、CD8+和PD-L1+细胞则呈广泛弥漫性分布。结论：PD-1、PD-L1、FOXP3和适应性调节性T细胞是促进CSCC发生发展的重要因素，其可作为ESCC免疫治疗的靶点和临床预后的潜在标志物。

[Abstract] Objective: To systematically evaluate the efficacy and safety of nivolumab plus ipilimumab versus nivolumab monotherapy in the treatment of malignant tumors, so as to provide evidence-based medical proof for clinical administration. Methods: Databases, such as PubMed, CNKI, VIP, and Wanfang Data, were searched from January 2000 to January 2022 to collect the clinical trial data in terms of nivolumab plus ipilimumab versus nivolumab monotherapy for malignant tumors were published in both domestic and abroad. Two reviewers independently evaluated the quality of included RCTs, and extracted and cross-checked the data. RevMan 5. 4 was used for the Meta-analysis. Results: A total of 7 RCTs studies including 10 articles were included. Compared with the nivolumab monotherapy group, the OS of patients in the combined treatment group was significantly improved (HR=0.86, 95% CI:0. 75-0.99, P=0. 03), and the PFS was significantly prolonged (HR=0.69, 95% CI: 0.55-0.85, P=0.000 6). However, as for safety, treatment-related adverse events (OR=3.18, 95% CI: 1.55-6.55, P=0.002) and adverse events leading to drug discontinuation (OR=7.11, 95% CI: 4.85-10.42, P<0.000 01) in the combination therapy group were significantly higher than those in the monotherapy group. Conclusion: Compared with nivolumab monotherapy, nivolumab plus ipilimumab can significantly improve the OS and PFS of tumor patients, but is also associated with more treatment-related adverse events and adverse events leading to drug discontinuation. Therefore, it is necessary to pay attention to follow-up and regular monitoring to prevent the occurrence of serious adverse reactions.

Objective:To analyze the therapeutic effect of adding interleukin (IL)-4Rα monoclonal antibody (duplizumab) to patients with multiple types of inflammatory diseases.Methods:Six patients with multiple types of inflammatory diseases who started to use duplizumab from August 2020 were enrolled. The changes of airway inflammation, lung function, sinuses computed tomography (CT), Asthma Control Questionnaire-5 (ACQ-5), Sino-Nasal Outcome Test-22 (SNOT-22), Pennsylvania Smell Identification Test (UPSIT) and Numerical Rating Scale (NRS) score before and after duplizumab treatment were retrospectively analyzed. All patients were treated with doprilumab for more than 5 months.Results:4 of the 6 patients had both severe asthma and chronic sinusitis, and 2 patients had both severe asthma, chronic sinusitis and atopic dermatitis. After treatment, the pulmonary function of 6 patients was improved, the levels of sputum eosinophils, exhaled nitric oxide and total IgE were decreased (all P<0.05), and the scores of paranasal sinus CT, ACQ-5, SNOT-22 and UPSIT were significantly improved (all P<0.05). However, 3 patients had increased peripheral blood eosinophils during the treatment. Conclusions:Duplizumab is effective for a variety of type 2 inflammatory diseases without obvious adverse reactions, and the peripheral eosinophils may increase during the treatment.

Objective To evaluate the feasibility and safety of prostatic artery embolization (PAE)via transradial approach in treating prostatic hyperplasia.Methods The clinical data of 18 patients with prostatic hyperplasia,who received C-arm CT-guided PAE via left or right radial artery access,were retrospectively analyzed.The following indexes were recorded:arterial spasm and injury of upper limbs,incidence of puncture point bleeding,postoperative radial artery pulse and congestion,blood supply and nerve injury of fingers,the surgical success rate,incidence of perioperative cerebral vascular complications,operation time,radiation dose and clinical curative effect.Results Among the 18 patients,PAE via left radial artery access was employed in 14,and PAE via right radial artery access was performed in 4.Bilateral PAE was carried out in 16 patients,and only unilateral PAE was able to be successfully accomplished in 2 patients as the prostatic artery opening of the other side was tortuous with stenosis.After PAE,decreased radial pulse was observed in one patient and ultrasound examination revealed decreased blood flow.The operation time ranged from 96 min to 245 min.The radiation dose received by the patient varied from 2435 mGy to 4958 mGy with a mean of (3342±156) mGy,which was not significantly different from the radiation dose received by the patients who underwent PAE via femoral artery access during the same study period (P=0.1167).Conclusion In treating prostatic hyperplasia,PAE by using transradial approach is clinically safe and technically feasible.