ObjectiveThis study aims to explore the effects of Huangqin Qingre Chubi capsules-containing serum on the expression of CircRNA_0001543/nuclear factor-kappa B （NF-κB） in co-cultured peripheral blood mononuclear cells （PBMCs） and human fibroblast-like synoviocytes （FLSs） from patients with ankylosing spondylitis （AS）. MethodsVenous blood was collected from patients with AS to isolate PBMCs. FLSs were co-cultured with AS patients' PBMCs， and FLSs were harvested after co-culture for subsequent experiments. The normal control group consisted of normal FLSs， while the model group comprised co-cultured AS PBMCs and FLSs to simulate AS pathology. The Huangqin Qingre Chubi capsules group involved adding Huangqin Qingre Chubi capsules-containing serum to the co-cultured cells（6.48 g·kg^-1）. To investigate the effect of HQC-containing serum on the viability of co-cultured cells， and the experiment was divided into the following groups based on the dilution concentration： blank group， 10% HQC group， 20% HQC group， and 30% HQC group.To study the influence of the optimal concentration of HQC-containing serum on cytokine and pathway indicators in each group， the experiment was divided into three groups： normal group， model group， and optimal concentration HQC-containing serum group.For the validation of the transfection efficiency of the CircRNA_0001543 interference plasmid， the experiment was divided into the following groups： blank group， si-NC group （with transfection reagent）， si-circ_0001543-1 group （with transfection reagent and interference plasmid No. 1 targeting circ_0001543）， si-circ_0001543-2 group （with transfection reagent and interference plasmid No. 2 targeting circ_0001543）， and si-circ_0001543-3 group （with transfection reagent and interference plasmid No. 3 targeting circ_0001543）.For the validation of the transfection efficiency of the CircRNA_0001543 overexpression plasmid， the experiment was divided into the following groups： blank group， OE-NC group （with transfection reagent）， and OE-circ_0001543 group （with transfection reagent and overexpression plasmid targeting circ_0001543）.To study the effects of CircRNA_0001543 interference/overexpression on cytokine and pathway indicators in each group， the experiment was divided into the following groups： si-NC group， si-CircRNA_0001543 group， OE-NC group， and OE-CircRNA_0001543 group. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of interleukin-1β （IL-1β）， IL-10， IL-37， and tumor necrosis factor-α （TNF-α）. Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to measure the expression of CircRNA_0001543， IκBα， and NF-κB p65. ResultsAfter 48 hours， 30% Huangqin Qingre Chubi Capsules-containing serum significantly inhibited the proliferation of co-cultured PBMCs and FLSs， which was determined to be the optimal experimental drug-containing serum concentration. Compared with those in the normal group， the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α in the model group were significantly increased （P<0.01）， while the expressions of CircRNA_0001543 mRNA， IL-10， and IL-37 were significantly decreased （P<0.01）. Compared with those in the model group， the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α in the Huangqin Qingre Chubi Capsules-containing serum group were significantly decreased （P<0.05）， and the expressions of CircRNA_0001543 mRNA， IL-10， and IL-37 were significantly increased （P<0.05）， with the most prominent changes in the 30% drug-containing serum group （P<0.01）. Compared with that in the si-NC group， the expression of CircRNA_0001543 was significantly reduced in the si-CircRNA_0001543 group （P<0.01）. Compared with that in the OE-NC group， the expression of CircRNA_0001543 was significantly increased in the OE-CircRNA_0001543 group （P<0.01）， indicating that the si-CircRNA_0001543 and OE-CircRNA_0001543 plasmids were successfully transfected. Based on the optimal drug-containing serum of Huangqin Qingre Chubi Capsules， si-CircRNA_0001543 transfection led to significantly increased expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α and decreased the expressions of IL-10 and IL-37 （P<0.01）. In contrast， OE-CircRNA_0001543 transfection significantly decreased the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α （P<0.01） and increased the expressions of IL-10 and IL-37 （P<0.01）. ConclusionHuangqin Qingre Chubi capsules-containing serum can improve immune inflammation in AS by increasing the expression of CircRNA_0001543， regulating the NF-κB pathway， suppressing pro-inflammatory cytokines， and enhancing anti-inflammatory cytokine expression.

AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.

Patients with severe tumors do not refer to the patients with end-stage tumors,but rather to the patients with a performance status(PS)score between 2 and 4 in certain stages due to various reasons,such as acute or chronic comorbidities,tumor itself,or treatment-related adverse events.To these patients,there is a high probability of achieving survival benefit and/or improvement in PS scores after synergistic management of available life-support technologies and anti-tumor therapies based on dynamic and precise testing.Elderly patients with tumors frequently present with one or more chronic illnesses and have poor toler-ance and compliance to treatment.Moreover,their treatment regimens often lack high-quality clinical evidence,making them more susceptible to developing severe tumors.The management of severe tumors in the elderly is based on three basic diagnosis and treatment technologies:dynamic and precise detection,powerful life support technologies,and skillful application of current anti-tumor treatments.In specific clinical practice,the following 7 flexible and individualized treatment strategies should be adopted for different tumor types:1.concurrent management of cancer and comorbidities,2.upgrading and downgrading of anti-tumor drugs based on PS score,3.dynamic accurate detection,4.skillful combinations for increasing efficacy and reducing toxicity,5.complete overview,paying equal attention to systemic therapy and local therapy,6.safety first in medication for the elderly,7.multi-discipli-nary participation,individualized and comprehensive treatment.This article introduced the concept of severe tumors in the elderly and the associated management strategies,to increase awareness and provide feasible guidance for clinical practice.

Objective:To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR.Methods:A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m 2 day 1, cisplatin 25 mg/m 2 days 1-3, and capecitabine 800 mg/m 2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results:A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm 3. The T stage ( OR=12.71, 95% CI: 1.4-112.5, P=0.022) and the volume ( OR=7.1, 95% CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion:The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Objective To explore the efficiency and safety of trans-sheath intraluminal forceps biopsy under digital subtraction angiography(DSA)guidance for assisting diagnosis of pulmonary artery obstructive diseases.Methods Data of 16 patients who underwent trans-sheath intraluminal forceps biopsy for pulmonary artery obstructive diseases were retrospectively analyzed,and the clinical manifestations were recorded.The technical success of biopsy was defined as tissue obtained met the needs of pathology diagnosis.For patients with malignant pathology results,the final diagnosis was malignant,for those with benign pathology results after biopsy and no obvious changes after 6-month or longer follow-up,or benign pathology results after surgical resection,the final diagnosis was benign,otherwise was no clear diagnosis.The operation time,technical success rate,diagnostic efficiency,complications and changes of pulmonary artery pressure before and after the biopsy were observed.Results Among 16 patients,9 complained of intermittent chest tightness,4 complained of chest pain with chest tightness,2 complained of chest pain but 1 denied any symptoms.The lesions located in the left lung in 10 cases and in the right lung in 6 cases,all with enhanced CT showed filling defects of the involved branch of pulmonary artery.Totally 16 trans-sheath intraluminal forceps biopsies were performed in 16 patients,with an average operation time of(31.02±6.02)min and technical success rate of 100%.Malignant tumors were finally diagnosed in 10 cases,including 1 case of lung cancer with false-negative biopsy result,while biopsy correctly diagnosed benign lesions in the other 6 cases.Transient worsening chest pain with chest tightness occurred in 2 cases and relieved after symptomatic treatments.No statistically significant difference of pulmonary artery pressure was found before([53.38±14.28]mmHg)and after([53.69±14.15]mmHg)biopsy(P＞0.05).Conclusion DSA-guided trans-sheath intraluminal forceps biopsy was relatively safe and valuable for assisting diagnosis of pulmonary artery obstructive diseases.

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

Background and objective Neoantigen reactive T cell(NRT)has the ability to inhibit the growth of tumors expressing specific neoantigens.However,due to the difficult immune infiltration and the inhibition of tumor micro en-vironment,the therapeutic effect of NRT in solid tumors is limited.In this study,we designed NRT cells(7×19 NRT)that can express both interleukin-7(IL-7)and chemokine C-C motif ligand 19(CCL19)in mouse lung cancer cells,and evaluated the difference in anti-tumor effect between 7×19 NRT cells and conventional NRT cells.Methods We performed next-generation sequencing and neoantigen prediction for mouse Lewis lung carcinoma(LLC),prepared RNA vaccine,cultured NRT cells,constructed retroviral vectors encoding IL-7 and CCL19,transduced NRT cells and IL-7 and CCL19 were successfully ex-pressed,and 7×19 NRT was successfully obtained.The anti-tumor effect was evaluated in vivo and in vitro in mice.Results The 7×19 NRT cells significantly enhanced the proliferation and invasion ability of T cells by secreting IL-7 and CCL19,achieved significant tumor inhibition in the mouse lung cancer and extended the survival period of mice.The T cell infiltration into tumor tissue and the necrosis of tumor tissue increased significantly after 7×19 NRT treatment.In addition,both 7×19 NRT treatment and conventional NRT treatment were safe.Conclusion The anti-solid tumor ability of NRT cells is significantly enhanced by the arming of IL-7 and CCL19,which is a safe and effective genetic modification of NRT.

Programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and PD-1 inhibitors plus chemotherapy combination regimens have been widely used in the first-line treatment of advanced non-small cell lung cancer(NSCLC), but patients with low PD-L1 expression have limited objective response and survival benefits. Existing treatment regimens are still difficult to fully meet the clinical needs of patients in the real world. Therefore, researchers are still exploring novel superactive treatment options to further improve the efficacy and survival prognosis of different sub-groups in NSCLC. Dual immunotherapy [such as the combination of PD-1 and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitors] has shown considerable long-term survival benefits in a variety of tumors and has also shown broad clinical prospects in NSCLC. In addition to exploring different emerging combination options, how to accurately identify the optimal-benefit groups through predictive biomarkers and how to effectively manage the safety of combination immunotherapy through multidisciplinary collaboration are also the focus of dual immunotherapy. This article reviews the mechanism of action, research progress, predictive biomarkers and future exploration directions of dual immunotherapy.
.
B7-H1 Antigen/metabolism* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Immunotherapy ; Lung Neoplasms/drug therapy* ; Prognosis

Objective : This experiment was carried out to study the effects of chronic inflammatory pain on the gut flora of mice by 16S rRNA high⁃throughput sequencing. Methods : Twelve specific pathogen free (SPF) C57BL/ 6J mice were randomly divided into CFA group and mock group , with 6 mice in each group. Chronic inflammatory pain model was established by intraplantar injection of CFA in the right posterior pelma of C57BL/6J mice. In the control group , normal saline was injected by intraplantar injection in the same position. Two weeks later, the mice were euthanized , and the feces in the colon were collected. The feces of two mice in the same group were mixed , detected and analyzed by 16S rRNA high⁃throughput sequencing technology. Results : Compared with mock group , the abundance and diversity of gut flora in CFA group decreased. The abundance of Firmicutes and TM7 increased at the phylum level , the abundance of Aerococcus , Lactobacillus and Desulfovibrio increased significantly at the fami ⁃ ly and genus level , while the abundance of Psychrobacter, Prevotella , Oscillospira and Bifidobacterium decreased significantly compared to mock group. In addition , many biomarkers were found from the level of the phylum to the genus. Conclusion The gut microflora structure , especially the dominant flora , has changed significantly in mice with chronic inflammatory pain , which can provide basis for the treatment of microecological imbalance caused by chronic inflammatory pain and the improvement of patients ′ negative emotions through“ gut brain axis”.

Objective:By comparing the clinical effect of minimally invasive hollow screw internal fixation Assisted by orthopedic robot (TiRobot) and O-arm navigation in the treatment of pelvic fractures, and practicability and security of both treatments were evaluated.Methods:Retrospective analysis of data of 42 cases of Tile C type pelvic fractures was employed during June 2017 to June 2020. Among them, 32 cases, twenty-four men, eight women, aged 34±6.2 years (range 24-68 years), were treated with percutaneous screw fixation guided by O-arm X wire instrument. According to Tile classification, there were 3 cases of C1.1 type, 8 cases of C1.2 type and 21case of C1.3 type. According to the Denis classification of sacral fractures, 17 cases were in zone I, and 8 cases in zone II. Ten patients, eight males and two females, aged 36±5.2 years (range 19-62 years) were treated by percutaneous screw fixation assisted by orthopedic robot. According to Tile classification, there were 1 case of C1.1 type, 2 cases of C1.2 type and 7 cases of C1.3 type. According to the Denis classification of sacral fractures, there were 5cases in zone I, 2 cases in zone II. For those who got obviously displaced pelvic fractures, Starr frames were used and then internal fixation was used to fix pelvic anterior ring and posterior ring injury respectively. Based on the times of needle adjustments, intraoperative fluoroscopy time, good screw position and incidence of complications two groups were statistically analysed. Matta score was employed to evaluate the quality of fracture reduction, while the Majeed score was employed to evaluate the clinical efficacy. Through the two groups of cases guide needle adjustment times, intraoperative fluoroscopy time, screw position excellent and good rate and the incidence of complications, which were statistically analyzed.Results:All screw positions were confirmed by CT scan after operation. The average time required for each screw placement of the O-arm group was 7.36±2.63 s, of the robot group was 6.80±3.20 s, so difference was not statistically significant ( P<0.05). An average of screw adjustments per one screw was 1.56±0.02 times by O-arm, and by the robot group was 0.34±0.06 times, so differences between the two groups were statistically significant ( P>0.05). The average operating time of O-arm group was 53.86±15.06 min, while the robot group was 52.52±15.14 min, so differences between the two groups were not statistically significant ( P>0.05). Position distribution of screw placement in two groups, all screws in O-arm group of position evaluations were excellent, excellent rate was 100%, all screw position evaluations by robot were excellent, excellent rate was 100%, so difference in screw distribution between the two groups was not statistically significant ( P>0.05). All cases were followed up for 6-12 months. Fracture healing time: 34.6±8.6 weeks for O-arm group, 33.4±9.4 weeks for robot group. Comparison between the two groups was not statistically significant ( P>0.05). Majeed score of O-arm group was 55-87, including Excellence of 17 cases, goodness of 9, fairness of 6. The rate of excellence and goodness was 81.2%, while robot group was 76-95, and that were excellent 7 cases,1 good, and the excellent and good rate was 80%, there was no significant difference between Matta and Majeed score between the two groups ( P>0.05). The incidence of complications between the two groups were no statistically significant ( P>0.05). Conclusion:Orthopedic robot system and O-arm navigation system assisted by percutaneous hollow screw fixation treatment of pelvic anterior and posterior ring injury, which are accurate, safe, minimally invasive, can reduce radiation damage to patients and surgeons. The efficacy were satisfactory. Both treatments are ideal for minimally invasive treatment of pelvic fractures, and the orthopedic robot have advantages of being programmed, standardized, stable and it’s learning curve is shorter.