The development and initial validation of IgG4-related disease damage index: a consensus report from Chinese IgG4-RD Consortium.

OBJECTIVE: To develop and conduct an initial validation of the Damage Index for IgG4-related disease (IgG4-RD DI). METHODS: A draft of index items for assessing organ damages in patients with IgG4-RD was generated by experts from the Chinese IgG4-RD Consortium (CIC). The preliminary DI was refined using the Delphi method, and a final version was generated by consensus. 40 IgG4-RD cases representing four types of clinical scenarios were then selected, each with two time points of assessment for at least 3 years of follow-up. 48 rheumatologists from 35 hospitals nationwide were invited to evaluate organ damage using the CIC IgG4-RD DI. The intraclass correlation coefficient (ICC) and the Kendall-W coefficient of concordance (KW) were used to assess the inter-rater reliability. The criterion validity of IgG4-RD DI was tested by calculating the sensitivity and specificity of raters. RESULTS: IgG4-RD DI is a cumulative index consisting of 14 domains of organ systems, including a total of 39 items. The IgG4-RD DI was capable of distinguishing stable and increased damage across the active disease subgroup and stable disease subgroup. In terms of scores at baseline and later observations by all raters, overall consistency in scores at baseline and later observations by all raters was satisfactory. ICC at the two time points was 0.69 and 0.70, and the KW was 0.74 and 0.73, respectively. In subgroup analysis, ICC and KW in all subgroups were over 0.55 and 0.61, respectively. The analysis of criterion validity showed a good performance with a sensitivity of 0.86 (95% CI 0.82 to 0.88), a specificity of 0.79 (95% CI 0.76 to 0.82) and an area under the curve of 0.88 (95% CI 0.85 to 0.91). CONCLUSION: The IgG4-RD DI is a useful approach to analyse disease outcomes, and it has good operability and credibility. It is anticipated that the DI will become a useful tool for therapeutic trials and studies of prognosis in patients with IgG4-RD.

A qualitative research exploring the experiences of patients receiving immune checkpoint inhibitors for advanced lung cancer.

PURPOSES: In patients with advanced lung cancer, immune checkpoint inhibitors (ICIs) dramatically extended survival. We aimed to investigate the experiences of patients with advanced lung cancer who are receiving ICIs, with a focus on perceptions and sentiments on ICIs, to inform future research and clinical care. METHODS: Patients were recruited from January to July 2022 at Tianjin Medical University Hospital Cancer Institute & Hospital. The method of purposive sampling was used. Patients with stage IV lung cancer who were taking ICIs as a single therapy were recruited. Data were gathered using semi-structured and face-to-face interview. An inductive approach to analysis was used. RESULTS: Of the 42 eligible patients, 27 were invited, 20 agreed to participate, and ultimately 17 patients completed the interview. A total of 5 themes were extracted: suffered from adverse effects but generally tolerable; focus on survival, hope, and expectation; uncertainty about durability of response and the future; poor knowledge and attitude of ICIs; and financial stress and guilt over family. CONCLUSION: These findings make an important contribution to healthcare professionals' understanding of what it is like to be a patient with advanced lung cancer who is receiving ICIs. In general, the experience of immunotherapy is different from that of chemotherapy; financial and family pressures and uncertainty issues are likely to be heavier in this population. Oncology specialist nurses should provide tailored education to improve the patient's knowledge of immunotherapy, especially to improve risk awareness of immune-related adverse events and objective prognosis expectations.

Effectiveness and safety of low-dose interferon alpha-2a treatment in Behçet's Syndrome with refractory vascular or neurological involvement: a case series.

Objective: The aim of this study was to evaluate the effectiveness and safety of low-dose interferon alpha-2a (IFNα2a) in Behçet's syndrome (BS) patients with refractory vascular/cardiac or neurological involvement. Methods: In this retrospective cohort study, we consecutively included 25 BS patients with refractory vascular/cardiac (n = 16) or neurological involvement (n = 9) who received IFNα2a treatment in our center between June 2018 and September 2021. The low-dose IFNα2a (3 million IU, every other day) was used as an add-on treatment with the continuation of glucocorticoids (GCs) and immunosuppressants. Results: In total, 25 patients (20 males, 5 females) with a mean age of 31.92 ± 9.25 years were included. IFNα2a was administered for BS patients with refractory vascular/cardiac involvement (n = 16) and neurological involvement (n = 9). Before the initiation of IFNα2a, patients had insufficient response or intolerance to conventional therapies. After a median follow-up of 23 [interquartile range (IQR), 11-30] months, all patients achieved clinical improvement. The Behçet's disease Current Activity Form (BDCAF) score improved significantly (5 versus 0, median, p < 0.0001). BS Overall Damage Index (BODI) and vasculitis damage index (VDI) remain stable (p > 0.05). Decrease in erythrocyte sedimentation rate [ESR; 24 (IQR, 12-43.5) versus 5 (IQR, 2.75-10.5) mm/h, p = 0.0001] and C-reactive protein [CRP; 6.64 (IQR, 3.67-19.82) versus 1.24 (IQR, 0.24-3.12) mg/liter, p < 0.005] was achieved effectively. The median GCs dosage tapered from 26.25 (IQR, 11.88-41.25) to 10.00 (IQR, 7.50-10.63) mg/d, p < 0.0001. Immunosuppressants were also reduced in number (p < 0.005). No serious adverse events were observed during follow-up. Conclusion: Our study suggests that low-dose IFNα2a, combined with GCs and immunosuppressants, is well-tolerated and effective for BS patients with refractory vascular/cardiac or neurological involvement and has a steroid- and immunosuppressant-sparing effect.

The clinical features, image findings and risk factors of vena cava syndrome in Behçet's syndrome.

OBJECTIVES: To investigate the clinical features, image findings, and potential risk factors of vena cava syndrome (VCS) in Behçet's syndrome (BS). METHODS: We conducted a case-control study in our BS registry database from 2012 to 2021. Fifty-five BS patients with VCS were enrolled in the case group, and two BS patients without VCS were selected as controls for each VCS case using risk-set-sampling. Multivariable logistic regression was used to detect the risk factors of VCS, and the outcome of these patients was also analysed. We also conducted an exploratory study to evaluate spectral computed tomography (CT) imaging in detecting thrombosis in BS patients with inferior VCS (IVCS). RESULTS: Multivariable logistic regression analysis revealed male gender (OR 11.16, 95%CI 3.34-37.32), early-onset BS (<18 years) (OR 5.57, 95%CI 1.58-19.69), ESR >60 mm/hr (OR 3.83, 95%CI 1.02-12.23) and pathergy reaction (OR 5.10, 95%CI 2.11-12.32) as potential risk factors of VCS in BS patients. For 4 BS patients with IVCS due to thrombosis, spectral CT found better contrast between IVC and thrombi at a low energy level of 40keV using virtual monoenergetic imaging than conventional images at 120kV. With a median follow-up of 3.3 years, the respective estimated 1- and 5-year survival rates were 96.3% and 94.2%, and respective estimated 1- and 5-year relapse-free rates were 93.9% and 78.0%. CONCLUSIONS: Male, early-onset BS, ESR >60 mm/hr, and pathergy reaction are potential risk factors of VCS in BS patients. Spectral CT is valuable in detecting thrombus in vena cava.

A novel label-free photoelectrochemical immunosensor based on CdSe quantum dots sensitized Ho3+/Yb3+-TiO2 for the detection of Vibrio parahaemolyticus.

A novel photoelectrochemical (PEC) immunosensor based on CdSe quantum dots (QDs) sensitized Ho3+/Yb3+-TiO2 for the detection of Vibrio parahaemolyticus (VP) was assembled. The working electrode was constructed via the layer-by-layer (LBL) method with the Ho3+/Yb3+-TiO2, CdSe QDs, NHS/EDC, antibody of VP (anti-VP), bovine serum albumin (BSA) modified on the surface of the FTO in sequence. Ascorbic acid (AA) acts as an electron donor to combine photogenerated holes in order to provide a stable current system. Ho3+ and Yb3+ co-doping TiO2 broadened the spectral response range of TiO2 to the infrared region and improved the photocurrent responsiveness of TiO2. The PEC immunosensor, with Ho3+/Yb3+ ratio of 1:5, Ho3+/Yb3+-TiO2 of 2 mg/mL and PBS solution of pH 7.4, had an optimal photocurrent responsiveness. Immobilization of anti-VP was by classical NHS/EDC coupling reactions between COOH groups of CdSe QDs and NH2 groups of the anti-VP. The results indicated that PEC immunosensors had a low detection limit of 25 CFU/mL, a wide detection range of 102-108 CFU/mL, high stability, low price, and short detection time. This method could be promising for the rapid and ultrasensitive detection of pathogenic microorganisms in the food.

[Effect of acupuncture at "reflection points" of the affected side on the peripheral facial paralysis in acute phase].

OBJECTIVE: To explore the effect of acupuncture at the "reflection points" of affected side on the peripheral facial paralysis in acute phase. METHODS: Ninety patients with peripheral facial paralysis in acute phase were randomly divided into a reflection group (group A), a conventional acupuncture group (group B) and a physiotherapy group (group C), 30 cases in each group. The same basic medication were given in all three groups. In the group A, acupuncture at "reflection points" of the affected side and local acupoints in acute phase, such as Dicang (ST 4), Jiache (ST 6), Quanliao (SI 18), Xiaguan (ST 7), Yangbai (GB 14), Taiyang (EX-HN 5), etc. were applied. The electroacupuncture was added in the stationary phase, and Zusanli (ST 36) was added in the recovery phase. In the group B, acupuncture at Yifeng (TE 17) of the affected side in acute phase and local acupoints, such as Dicang (ST 4), Jiache (ST 6), Quanliao (SI 18), Xiaguan (ST 7), Yangbai (GB 14), Taiyang (EX-HN 5), etc. were applied. The electroacupuncture was added in the stationary phase, and Zusanli (ST 36) was added in the recovery phase. In the group C, ultrashort wave on Yifeng (TE 17) of the affected side in acute phase was applied, and the treatment in the stationary phase and the recovery phase was the same as the group B. The treatment was given once every day, 5 times as one course for 4 courses. The House-Brackmann (H-B) grading scale, facial disability index scale, the symptom and physical score integral scale were used to score before and after treatment, and the clinical effects of the three groups were compared. RESULTS: After treatment, the functional grade of H-B facial nerve was better than that before treatment in the three groups (P<0.01). There was no significant difference among the three groups after treatment (P>0.05). After treatment, the course of treatment required to reflect the healing in the group A was shorter than that in the group B and the group C (P<0.01); the body function scores and social function scores in the three groups were better than those before treatment (P<0.01), there was no significant difference among the three groups after treatment (P>0.05). The scores of symptoms and signs in the three groups were lower than those before treatment (P<0.01), there was no significant difference among the three groups after treatment (P>0.05). H-B facial nerve function grading scale and facial disability index (FDI) scale were used as the evaluation criteria, the curative rate was 66.7% (20/30) in the group A, 50.0% (15/30) in the group B and 46.7% (14/30) in the group C, the curative rate in the group A was better than the other two groups (P<0.05). The curative and markedly effective rate in the group A was 83.3% (25/30), 70.0% (21/30) in the group B and 63.3% (19/30) in the group C, the curative and markedly effective rate in the group A was better than the other two groups (P<0.05). The scores of symptoms and signs were used as the evaluation criteria, the curative rate was 66.7% (20/30) in the group A, 50.0% (15/30) in the group B, and 46.7% (14/30) in the group C. The curative rate in the group A was better than the other two groups (P<0.05). CONCLUSION: Compared with general acupuncture and physiotherapy, acupuncture at the "reflection points" of the affected side on the peripheral facial paralysis in acute phase could shorten the course of treatment and improve the curative effect.

Delayed Dural Arteriovenous Fistula at the Transverse-Sigmoid Sinus Secondary to Petroclival Meningioma Surgery Via Far Lateral Approach.

Intracranial dural arteriovenous fistulas (DAVFs) are typified by pathological anastomoses between meningeal arteries and dural venous sinuses or cortical veins. There are many causes contributing to the etiology of DAVFs. Among the variable causes, acquired DAVFs secondary to craniotomy had rarely been reported, especially for delayed DAVFs at the transverse-sigmoid sinus. Till now, there are only 12 published cases of delayed DAVFs at the transverse-sigmoid sinus secondary to craniotomy. Herein, the authors describe such an extraordinary rare case secondary to petroclival meningioma resection via far lateral approach, and to the best knowledge of us, this is the first well-documented case of delayed DAVF at the transverse-sigmoid sinus following far lateral craniotomy. Furthermore, cases of delayed DAVFs at the transverse-sigmoid sinus secondary to craniotomy were reviewed and investigated, and the clinical characteristics and treatment were also broadly discussed.

Application values of miR-194 and miR-29 in the diagnosis and prognosis of gastric cancer.

The object of this study was to analyze the expression of miR-194 and miR-29 in gastric cancer and their roles in the regulation of malignant phenotype of gastric cancer cells, and to explore the application value of miR-194 and miR-29 in diagnosis and prognosis of gastric cancer. Tumor tissue and adjacent healthy tissue of 165 gastric cancer patients diagnosed by pathologic examinations were collected. Expression of miR-194 and miR-29 in the tissues was detected by RT-PCR. The relationship between miR-194 and miR-29 expression and clinical data was analyzed. SGC7901 cells were treated with miR-194 and miR-29 mimics, respectively. Effects of miR-194 and miR-29 on proliferation and invasion of SGC7901 cells were investigated. Expression levels of miR-194 and miR-29 in tumor tissue were lower than those in adjacent tissues (P<0.001). There was no significant difference in expression level of miR-194 and miR-29 in cancer tissues derived from gastric cancer patients in different age and gender groups (P>0.05). Expression of miR-194 and miR-29 in tumor tissue was closely related to TNM stage, differentiation degree of cancer cells and lymph node metastasis (P<0.05). Proliferation and migration of SGC7901 cells were significantly inhibited by miR-194 mimic and miR-29 mimic transfection (P<0.05). miR-194 and miR-29 are downregulated in gastric cancer, and the expression levels of miR-194 and miR-29 were closely related to tumor differentiation and metastasis. Overexpression of miR-194 and miR-29 significantly inhibited the proliferation and migration of gastric cancer. The detection of the expression of miR-194 and miR-29 can provide basis for the diagnosis and prognosis of gastric cancer.

[A Case Report of Advanced Lung Adenocarcinoma Harboring KRAS Mutation 
Treated with Anlotinib].

In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. ALTER0303 trail, phase III study has demonstrated that Anlotinib significantly prolonged overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients as 3rd line treatment.Here we report a case of advanced lung adenocarcinoma harboring KRAS mutation treated with Anlotinib.
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Effects of cryopreservation at various temperatures on the survival of kelp grouper (Epinephelus moara) embryos from fertilization with cryopreserved sperm.

Fish embryo cryopreservation is highly important for the long-term preservation of genomic and genetic information; however, few successful cases of fish embryo cryopreservation have been reported over the past 60 years. This is the first study to use Epinephelus moara embryos from fertilization with cryopreserved sperm as experimental material. Embryos that developed to the 16-22 somite stage and tail-bud stage were treated with the vitrification solution PMG3T according to a five-step equilibration method and cryopreserved at various temperatures and storage duration. Only 19.9 ± 9.2% of 16-22 somite stage embryos and 1.3 ± 1.1% of tail-bud stage embryos survived when cooled at 4 °C for 60 min. In total, 8.0 ± 3.0% of 16-22 somite stage embryos survived when cooled at -25.7 °C for 30 min, 22.4 ± 4.7% of tail-bud stage embryos survived after 45 min of cooling at -25.7 °C, and none survived after 60 min. Only 2.0 ± 2.7% of embryos survived when cryopreserved at -140 °C for 20 min. However, 9.7% of tail-bud stage embryos survived after cryopreservation in liquid nitrogen (-196 °C) for 2 h. Most surviving embryos developed normally. Embryonic volume decreased and spherical segments appeared when embryos were treated with higher concentrations of vitrification solution. Additionally, the volume recovered gradually after rinsing with sucrose and seawater. This is the first estimate of the survival of E. moara embryos and larvae after cryopreservation. These findings provide a foundation for further explorations of fish embryo cryopreservation techniques.

Effects of color centers absorption on the spectrum of the temperature-dependent radiation-induced attenuation in fiber.

Spectra ranging from 800 to 1650 nm of the temperature-dependent radiation-induced attenuation (RIA) in the irradiated and sufficiently annealed fiber with germanium and phosphorous dopant has been measured. These RIA spectra were investigated based on the mechanism of color centers absorption. With the configurational coordinate model, these RIA spectra were decomposed by the absorption bands of three kinds of color centers. The effects of color centers absorption on the spectrum of temperature-dependent RIA is discussed by comparing the absorption intensity of different color centers at a same wavelength. Moreover, the temperature-dependent RIA of the fiber has been measured separately at 850, 1310, and 1550 nm. The measured results agreed well with the analysis of RIA spectra.

[Accurate and rapid prenatal diagnosis of beta-thalassemia by a multiplex primer extension and denaturing high-performance liquid chromatography technique].

OBJECTIVE: To develop a primer-extension in combination with denaturing high-performance liquid chromatography (PE-DHPLC)-based assay for prenatal diagnosis of the five most common beta-thalassemia mutations in Chinese. METHODS: The human beta-globin gene fragment was amplified by PCR, followed by a multiple PE reaction specific for each five mutations. Then the PE product mixtures were separated for genotyping of beta-globin gene mutations using fully-denaturing DHPLC analysis. RESULTS: In a blind study, prenatal diagnosis was performed on thirty-six at-risk families for beta-thalassemia major. Reverse dot blot (RDB) analysis was used to validate each result, showing an accuracy rate of 100% for PE-DHPLC in a total of 108 samples tested. Overall, by PE-DHPLC analysis, the authors could identify the genotypes involving the five mutations and normal alleles corresponding to 94.4% (102/108) and actually make final decision for prenatal diagnosis covering 97.2% (35/36). CONCLUSION: The PE-DHPLC protocol can be a simple, rapid, and highly accurate assay in the prenatal detection of common beta-thalassemia mutations.

[A case control study on the risk factors of male infertility].

OBJECTIVE: To study the risk factors of male infertility. METHOD: Case control study including 94 cases and control group with a ratio of 1 to 1. RESULTS: The risk factors of male infertility were long time heavy smoking habit (OR = 3.45, 95% CI: 1.95 - 6.10), illegal sexual intercourse (OR = 7.29, 95% CI: 2.54 - 20.89), growing vegetable under plastic in higher temperature (OR = 6.73, 95% CI: 1.91 - 23.69), contact with benzene chemicals (OR = 20.53, 95% CI: 4.67 - 90.25) and having Ureaplasma urealyticum (Uu) infection (OR = 5.55, 95% CI: 2.28 - 13.53). CONCLUSION: Male infertility was resulted from many factors repeatedly acting on men for long time. In order to prevent male infertility, issues as environmental pollution, occupational protection need to be improved while bad working condition and risky behavior should be changed.

[Application of phage antibody library technology: problems and their solutions].

In spite of the wide application of phage antibody library technology in antibody engineering, problems are often present especially in the key steps, for instance, library construction, screening and expression of the antibody. The authors conducted an analysis of these problems and thereby proposes their solutions.

Expression of phospholipase-gamma1 in human fetal tissues.

OBJECTIVE: To investigate the expression of phospholipase C-gamma1(PLC-gamma1) in human fetal tissues. METHODS: Serial sections 5 &mgr;m in thickness were prepared from paraformadehyde-fixed and paraffin-embedded normal human fetal tissues including the cartilage, the cartilage membrane and the muscle tissues. The distribution of PLC-gamma1 expression was examined immunohistochemically in the sections. RESULTS: Immunoreactive PLC-gamma1 was readily detected in the cells of the cartilage, the cartilage membrane and the muscl tissues, which was largely confined within the cytoplasm. CONCLUSION: PLC-gamma1 is essential for the early development and cell proliferation of human embryos.