To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

Objective:To investigate the value of antioxidant-associated long non-coding RNAs(lncRNAs)risk score model in prognosis and the association with immune microenvironment of the gastric cancer patients.Methods:Gastric cancer transcriptome data and clinical information were downloaded from TCGA database.Antioxidant-associated lncRNAs were obtained by co-ex-pression analysis of lncRNAs and antioxidant genes.Risk score was constructed using univariate cox regression analysis and lasso regression analysis.Log-Rank test was used to compare the survival differences between two groups.Receiver operating characteristic curve(ROC)was used to assess the specificity and sensitivity of the prognostic risk score model.Nomogram was constructed com-bining risk score and clinical parameters.Immune cell infiltration was assessed by TIMER 2.0.Im-munotherapy sensitivity of each sample was analyzed at TIDE website.Results:A risk score in-cluding 12 IncRNAs was constructed by univariate cox regression analysis and lasso regression anal-ysis.The risk score was an independent factor influencing patient prognosis[HR=5.406(3.131～9.335),P＜0.001].Risk score was positively correlated with multiple suppressive immune cells infil-tration(M2 macrophage,tumor-associated fibroblast).Meanwhile,multiple aberrant expression of immune checkpoint genes and higher TIDE score were found in high-risk group,suggesting that high-risk groups may be more sensitive to immunotherapy.Conclusion:The antioxidant-associ-ated IncRNAs risk score is a good prognostic predictor and can act as a reference in individualized immunotherapy for gastric cancer patients.

Humans ; Gemcitabine ; Neoplasms

Objective: We aimed to explore the feasibility of a single-port thoracoscopy- assisted five-step laparoscopic procedure via transabdominal diaphragmatic(TD) approach(abbreviated as five-step maneuver) for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma (AEG). Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) age 18-80 years; (2) diagnosis of Siewert type II AEG; (3) clinical tumor stage cT2-4aNanyM0; (4) meeting indications of the transthoracic single-port assisted laparoscopic five-step procedure incorporating lower mediastinal lymph node dissection via a TD approach; (5) Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1; and (6) American Society of Anesthesiologists classification I, II, or III. The exclusion criteria included previous esophageal or gastric surgery, other cancers within the previous 5 years, pregnancy or lactation, and serious medical conditions. We retrospectively collected and analyzed the clinical data of 17 patients (age [mean ± SD], [63.6±11.9] years; and 12 men) who met the inclusion criteria in the Guangdong Provincial Hospital of Chinese Medicine from January 2022 to September 2022. No.111 lymphadenectomy was performed using five-step maneuver as follows: superior to the diaphragm, starting caudad to the pericardium, along the direction of the cardio-phrenic angle and ending at the upper part of the cardio-phrenic angle, right to the right pleura and left to the fibrous pericardium , completely exposing the cardio-phrenic angle. The primary outcome includes the numbers of harvested and of positive No.111 lymph nodes. Results: Seventeen patients (3 proximal gastrectomy and 14 total gastrectomy) had undergone the five-step maneuver including lower mediastinal lymphadenectomy without conversion to laparotomy or thoracotomy and all had achieved R0 resection with no perioperative deaths. The total operative time was (268.2±32.9) minutes, and the lower mediastinal lymph node dissection time was (34.0±6.0) minutes. The median estimated blood loss was 50 (20-350) ml. A median of 7 (2-17) mediastinal lymph nodes and 2(0-6) No. 111 lymph nodes were harvested. No. 111 lymph node metastasis was identified in 1 patient. The time to first flatus occurred 3 (2-4) days postoperatively and thoracic drainage was used for 7 (4-15) days. The median postoperative hospital stay was 9 (6-16) days. One patient had a chylous fistula that resolved with conservative treatment. No serious complications occurred in any patient. Conclusion: The single-port thoracoscopy-assisted five-step laparoscopic procedure via a TD approach can facilitate No. 111 lymphadenectomy with few complications.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Diaphragm/surgery* ; Retrospective Studies ; Feasibility Studies ; Esophagogastric Junction/surgery* ; Lymph Node Excision/methods* ; Stomach Neoplasms/pathology* ; Laparoscopy/methods* ; Gastrectomy/methods* ; Esophageal Neoplasms/pathology* ; Adenocarcinoma/pathology* ; Thoracoscopy

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

AIM: To investigate the influencing factors of vault after the posterior chamber phakic refractive lens(PC-PRL)implantation for patients with super high myopia.METHODS: Retrospective case study. A total of 40 patients with super high myopia(77 eyes)who underwent PC-PRL implantation in the Haixiang Eye Hospital from January 2019 to January 2021 were selected. They were followed up for at least 2a, postoperative anterior segment parameters, such as the uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), central anterior chamber depth(ACD), anterior chamber volume(ACV), anterior chamber angle(ACA), lens thickness and vault were evaluated, and then the influencing factors of postoperative vault were analyzed.RESULTS: The UCVA and BCVA of the patients significantly improved after PC-PRL implantation(P<0.001). Average safety index(postoperative BCVA/preoperative BCVA)was 1.36±0.32, and average effective index(postoperative UCVA/preoperative BCVA)was 1.23±0.31 in 2a after surgery. The vault in 2a after surgery was correlated with preoperative ACD, ACV, ACA and lens thickness, and the preoperative ACV and lens thickness had significant impact on vault in 2a after surgery.CONCLUSIONS: The PC-PRL implantation is safe and effective in super high myopia, and it can significantly improve visual acuity. Furthermore, preoperative ACV and lens thickness are important influencing factors of postoperative vault.

In recent years, laparoscopic surgery and robotic surgery have been widely used, and various intraoperative image navigation systems have also developed rapidly. However, the liver itself has a complex vessel and duct system, which increase the difficulty of liver surgery. The augmented reality image navigation system combines the three-dimensional reconstructed image of the liver with the real liver anatomy, which presents the specific relationship between the tumor location and the surrounding vessels for the surgeon. Compared with other intraoperative image navigation methods, augmented reality has its unique advantages. This paper provides an overview of current advances in registration technology in augmented reality image navigation system, and focuses on its applications in liver surgery, including laparoscopic surgery and robotic surgery. Finally, the technological problems and difficulties still faced at present are summarized, and future directions worth studying in this field are proposed.

OBJECTIVE: To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients. METHODS: Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP). RESULTS: The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05). CONCLUSION For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.
Humans ; Aged ; Methotrexate/adverse effects* ; Retrospective Studies ; Temozolomide/therapeutic use* ; Central Nervous System Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Central Nervous System

Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)pro-duction and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1α(HIF-1α),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endo-thelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H2O2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1α,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
Male ; Child ; Female ; Humans ; Child, Preschool ; Receptors, Tumor Necrosis Factor, Type I/genetics* ; Retrospective Studies ; Hereditary Autoinflammatory Diseases/drug therapy* ; Glucocorticoids/therapeutic use* ; Biological Factors/therapeutic use* ; Immunosuppressive Agents/therapeutic use* ; Autoantibodies ; Familial Mediterranean Fever/diagnosis* ; Mutation