AIM: To evaluate the diagnostic value of serum Th1-type cytokine levels and extraocular muscle-related parameters in thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective study was conducted on 45 patients diagnosed with TAO in our hospital from January 2023 to December 2024, and 20 normal volunteers during the same period as controls. Venous blood samples of the patients were collected to detect the concentrations of Th1-type cytokines [interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), and interleukin-12(IL-12)] in the serum. Additionally, the end diastolic velocity(Ved), velocity maximum(Vmax), resistance index(RI)of the central retinal artery, as well as the thickness and left-right diameter of the medial rectus muscle were measured. Logistic regression model was used to analyze the risk factors of TAO, and receiver operating characteristic curve(ROC)was adopted to evaluate the diagnostic efficacy of each index for the occurrence of TAO.RESULTS: The general information of the two groups was comparable. Compared with the normal control group, the serum concentrations of IFN-γ and TNF-α in TAO patients were significantly increased, Ved and Vmax were lower than those in the control group, and RI and the thickness of the medial rectus muscle were higher than those in the control group(all P<0.05). Logistic regression analysis showed that serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle were all risk factors for TAO. ROC curve analysis indicated that the AUCs of serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle for the diagnostic efficacy of TAO were 0.756, 0.769, 0.732, and 0.642, respectively. The combined detection of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle had an AUC of 0.840 and a Youden index of 0.59, which was superior to the detection of a single indicator.CONCLUSION: The levels of serum Th1-type cytokines and extraocular muscle-related ultrasound indicators have certain value in the diagnosis of TAO. The combination of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle has better diagnosis efficiency in TAO, which can provide a certain reference for the early diagnosis of TAO.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective:To investigate the clinical efficacy and safety of ZR2 (zevalin + lenalidomide + rituximab) regimen in the treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was conducted. The clinical data of 16 elderly (>65 years old) non-germinal center B-cell-like DLBCL patients treated with ZR2 regimen at the Taixing People's Hospital from January 2021 to March 2023 were retrospectively analyzed. The efficacy, adverse reactions and prognosis of patients were observed.Results:Of the 16 patients, 11 were male and 5 were female, with the age [ M ( Q1, Q3)] of 76 years old (70 years old, 78 years old), and 10 cases were Ann Arbor stage Ⅲ-Ⅳ. Among the 16 patients, 9 achieved complete remission, 4 patients achieved partial remission. All 16 patients experienced varying degrees of reversible bone marrow suppression, grade Ⅲ-Ⅳ hematologic adverse reactions included neutropenia (7 cases) and thrombocytopenia (2 cases), and the bone marrow hematopoiesis recovered after treatment with granulocyte colony-stimulating factor and thrombopoietin. The main ≥grade Ⅱ non-hematologic adverse reactions were gastrointestinal reactions (5 cases), liver function abnormalities (3 cases) and peripheral neuropathy (2 cases), which were improved after the appropriate treatment. Two patients discontinued the treatment of this regimen due to disease progression, and 1 patient died from complications after 2 cycles of treatment. No deep vein thrombosis, cardiac toxicity or renal toxicity occurred during the treatment process. Conclusions:The ZR2 regimen is effective in the treatment of elderly DLBCL patients with tolerable adverse reactions.

Objective:To investigate the current status of vocational training for pediatric clinical research coordinators (CRC), and discuss the construction of base-based pediatric CRC training, and to promote the ability of pediatric CRCs.Methods:From July 25 to October 16, 2023, an anonymous self-designed questionnaire survey was conducted through the Wenjuanxing platform to investigate the current situation of pediatric CRC vocational training and base training needs. The data were collated using Excel. Categorical data were described as numbers and percentages.Results:A total of 328 usable questionnaires were returned. Only 7.62% (25 people) believed that existing CRC training was sufficient and could meet actual work needs; 4.88% (16 people) responded that there was no training; 46.34% (152 people) believed that the training was insufficient to support actual work needs; 87.50% (287 people) believed that continuous CRC training was needed; 46.95% (154 people) preferred experienced CRCs for teaching, who should have at least 3 years of CRC work experience; and 46.95% (154 people) preferred a duration of 3 months for CRC training. The preferred training methods were: practice under the direction of experienced CRCs (90.85%, 298 people), step-by-step teaching of practical skills (88.41%, 290 people), case analysis and discussion (87.20%, 286 people), process simulation (83.23%, 273 people), and lecture-based teaching (76.52%, 251 people). The preferred post-training assessment methods were: case analysis (76.52%, 251 people), operation simulation (74.09%, 243 people), process simulation (73.17%, 240 people), written examination (66.16%, 217 people), and interview (63.72%, 209 people).Conclusions:The current pediatric CRC training is not enough to meet actual work needs. It is urgent to develop and promote a CRC training system that can meet work needs, laying the foundation for the construction of pediatric clinical research ecology in China.

Objective:To explore the effect of complement component C1s on the proliferation,migration and adhesion of esophageal squamous cell carcinoma(ESCC)cells and on the growth of xenograft tumors in nude mice.Methods:The C1S mRNA ex-pression of ESCC tissues and adjacent normal tissues(ANTs)were analyzed using NCBI-GEO database.The C1s expression of ESCC cell lines was analyzed with RT-qPCR and Western blot.The knockdown or overexpression of C1s in ESCC cells lines was performed using C1s small interfering RNA(siRNA),C1s short hairpin RNA(shRNA)or C1s overexpression lentivirus,and the cell prolifera-tion was detected by CCK-8 assay,cell migration was detected by cell wound healing assay,cell adhesion was detected by cell-matrix adhesion assay,the expressions of matrix metalloproteinases MMP1 and MMP13 were detected by Western blot,and the effect of C1s on the growth of xenograft tumors in nude mice was detected by subcutaneous tumorigenesis assay in nude mice.The expression of CD34 in the xenograft tumors was detected by immunohistochemistry,and the formation of tumor microvessel was analyzed.Results:The expression of C1S mRNA in ESCC tissues was significantly higher than that in ANTs.Knockdown of C1s significantly suppressed proliferation,migration and cell-matrix adhesion of ESCC cells,as well as growth of xenograft tumors in nude mice,while overexpres-sion of C1s had the opposite effects.The expressions of MMP1 and MMP13 were decreased in ESCC cells TE-1 with C1s knockdown.Compared with control group,the microvessel of the xenograft tumors in the C1s overexpression group were more abundant.Conclu-sion:C1s is significantly upregulated in ESCC tissues,and promotes proliferation,migration,cell-matrix adhesion of ESCC cells,and the growth of xenograft tumors.C1s may play an important role in the occurrence and development of ESCC.

Objective To investigate the effect of miR-130a targeting phosphase and tensin homology deleted on chromosome ten(PTEN)/phosphoinositide 3 kinase(PI3K)/protein kinase B(AKT)pathway on renal tissuecell apoptosis in diabetic kidney disease(DKD)rats.Methods The DKD rat model was constructed by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).72 rats were divided into normal control group(NC),DKD model group(DKD),miR-130a agonist negative control group(NC agomir),and miR-130a agonist group(miR-130a agomir),miR-130a agomir+ PTEN overexpression negative control group(miR-130a agomir+pcDNA),and miR-130a agomir+ PCDNA-PTEN overexpression group(miR-130a Agomir + PCDNA-PTEN),with12 rats in each group.Urinary microalbumin kit was used to detect 24 h urine albumin(UAlb).Fasting blood glucose(FBG),serum creatinine(Scr)and blood urea nitrogen(BUN)were detected by automatic biochemical analyzer.Pathological changes of renal tissue were detected by HE staining.The levels of serum IL-6 and TNF-α were detected by ELISA.The apoptosis of renal tissue was detected by TUNEL staining.The expression of miR-130a was detected by qRT-PCR,and the expression of B-cell lymphoma-2-associated X protein(Bax),B-cell lymphoma-2(Bcl-2)and PTEN/PI3K/AKT pathway were detected by Western blot.Dual luciferase reporter gene experiment was used to verify the targeting relationship between miR-130a and PTEN.Results Compared with DKD and NC agomir groups,24 h UAlb,FPG,Scr,BUN,IL-6,TNF-α,renal cell apoptosis rate,Bax protein expression and PTEN protein expression in miR-130a agomir group were decreased(P＜0.05).The expressions of miR-130a,Bcl-2,p-Akt/AKT protein were increased(P＜0.05).Compared with miR-130a agomir group,24 h UAlb,FPG,Scr,BUN,IL-6,TNF-α,renal cell apoptosis rate,Bax protein expression and PTEN protein expression were increased in miR-130a agomir+pcDNA-PTEN group(P＜0.05).The expression of Bcl-2,p-Akt/AKT protein decreased(P＜0.05).Conclusion Overexpression of miR-130a may inhibit renal cell apoptosis in DKD rats by down-regulating PTEN to activate PI3K/AKT pathway.

Objective:To observe the clinical efficacy and safety of Tongren Niuhuang Qingxin Pills combined with telmisartan tablets in the treatment of hypertensive vertigo syndrome of phlegm-heat disturbance.Methods:Randomized controlled trial was conducted. Totally 80 patients with hypertension vertigo and phlegm-heat disturbance syndrome were selected from March 2021 to August 2022 at Beijing Tongrentang Hospital of Traditional Chinese Medicine as the observation objects. They were randomly divided into two groups using a random number table method, with 40 cases in each group. The control group received oral telmisartan tablets, while the experimental group received Tongren Niuhuang Qingxin Pills in addition to the control group. Both groups were treated for 28 days and followed up for 1 month. The patients' room blood pressure before and after treatment was measured, and TCM syndrome scores were evaluated. The dizziness assessment rating scale (DARS) was used to evaluate the severity of dizziness, adverse reactions during treatment were recorded, drug safety was observed, and clinical efficacy was evaluated.Results:The total effective rate of the experimental group was 85.0% (34/40), and that of the control group was 7.5% (3/40), with statistical significance between the two groups ( χ2=48.32, P<0.001). Compared with before treatment, the experimental group had SBP [(136.63 ± 6.01) mmHg vs. (159.30 ± 9.01) mmHg, t=-21.00] and DBP [(84.48 ± 4.36) mmHg vs. (95.30 ± 3.75) mmHg, t=-13.80] after treatment; after treatment, SBP [(137.34 ± 6.39) mmHg vs. (158.00 ± 10.06) mmHg, t=-5.28] and DBP [(86.08 ± 4.43) mmHg vs. (95.18 ± 6.61) mmHg, t=-8.09] decreased in the control group ( P<0.01), but there was no statistical significance between the two groups after treatment ( P>0.05). After treatment, the TCM syndrome scores in the experimental group (8.68 ± 3.39 vs. 15.12 ± 3.03, Z=-6.61) were lower than those in the control group ( P<0.001), and DARS score [(8.53 ± 3.93) vs. (12.20 ± 3.95), Z=-3.63] was lower than that in the control group ( P<0.001). After treatment, the therapeutic effect index of TCM syndromes in the experimental group improved compared to before treatment in the same group. The therapeutic effect index of each symptom, from high to low, was as follows: rotation of oneself or visual objects>numbness of limbs>dry stool>dizziness and dizziness>liking cold drinks>bitter and dry mouth>red urine>red tongue, yellow coating, and greasy tongue>vomiting sticky and turbid phlegm>tinnitus>smooth pulse. There were no significant adverse reactions during the treatment of the two groups. Conclusion:Tongren Niuhuang Qingxin Pills combined with telmisartan can reduce the blood pressure of patients with hypertensive vertigo syndrome of phlegm-heat disturbance, improve the vertigo symptoms and TCM syndromes of patients, and the efficacy evaluation is superior to that of telmisartan alone.

OBJECTIVE To investigate the changes in high performance liquid chromatography （HPLC） fingerprint spectra and nucleoside components between Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and its processed product Succus bambusae pinella preparata， providing a reference for the quality evaluation of the latter. METHODS HPLC fingerprint was established for 10 batches of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and its processed product Succus bambusae pinella preparata following the Similarity Evaluation System of TCM Chromatographic Fingerprints （2012 Edition）. Hierarchical cluster analysis （HCA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS- DA） were conducted on their common peaks. The contents of four nucleoside components， hypoxanthine， uridine， adenine， and guanosine， in both Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata were determined. RESULTS The similarity between the fingerprints of the 10 batches of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine， Succus bambusae pinella preparata， and their corresponding reference fingerprints ranged from 0.851 to 0.990. A total of 10 common peaks were obtained for both samples， and 4 components were identified as hypoxanthine， uridine， adenine， and guanosine. The results of HCA， PCA and OPLS-DA showed that the samples of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata were clustered into separate categories， with OPLS-DA selecting 4 differential components between them， ranked by variable importance projection values as peak 8， peak 1， peak 6 （adenine） and peak 10. The content determination results showed that the average contents of hypoxanthine， uridine， adenine and guanosine in Succus bambusae pinella preparata declined by 15.90%， 12.00%， 26.04% and 22.18% compared to Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine， respectively， with statistically significant differences in the contents of hypoxanthine， adenine and guanosine （P＜0.05 or P＜0.01）. CONCLUSIONS The established fingerprint and content determination methods are simple to operate and have good repeatability， which are suitable for qualitative and quantitative analysis of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Succus bambusae pinella preparata. The average contents of the four nucleoside components decreased after the processing of Succus bambusae pinella preparata.

Objective This study aimed to investigate the temporal and spatial changes in the expression of perios-tin during periodontal inflammation in mice.Methods A periodontitis model was constructed using silk thread ligation.Mice were randomly divided into five groups in-cluding control group,4-day ligation group,7-day liga-tion group,14-day ligation group,and self-healing group(thread removal for 14 days after 14-day ligation).Mi-cro-CT and histological staining were performed to char-acterize the dynamic changes in the mouse periodontal tissue in each group.RNAscope and immunohistochemical staining were used to analyze the pattern of changes in peri-ostin at various stages of periodontitis.The cell experiment was divided into three groups:control group,lipopolysac-charide(LPS)stimulation group(treated with LPS for 12 h),and LPS stimulation removal group(treated with LPS for 3 h followed by incubation with medium for 9 h).Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of periostin,transforming growth factor-β1(TGF-β1),and matrix metalloproteinase 2(MMP2).Results Significant alveolar bone resorption was observed 7 days after ligation.With increasing duration of ligation,the damage to the mouse periodontal tissue was aggravated,which manifested as increased osteoclasts,widen-ing of the periodontal membrane space,and decreased alveolar bone height.Some degree of periodontal tissue repair was observed in the self-healing group.Periostin expression decreased at 4 and 7 days compared with the control group and increased at 14 days compared with 4 and 7 days.A significant recovery was found in the self-healing group.The qRT-PCR results showed that the expression of periostin and TGF-β1 in the LPS stimulation group decreased compared with that in the control group but significantly recovered in the LPS removal group.Conclusion Periostin expression in the PDL of mice showed a downward and upward trend with inflammation progression.The significant recovery of periostin expression after removing inflammatory stimuli may be related to TGF-β1,which is crucial to maintain the in-tegrity of the PDL.

Objective:To retrieve, evaluate, and integrate the best evidence for prevention of hemodialysis catheter thrombosis, so as to provide evidence-based basis for catheter thrombosis prevention in hemodialysis patients.Methods:Guidelines, clinical decisions, evidence summaries, systematic reviews, and expert consensus on the prevention of hemodialysis catheter thrombosis were systematically searched on Guidelines International Network, Scottish Intercollegiate Guidelines Network, Agency for Healthcare Research and Quality, Registered Nurses' Association of Ontario, National Institute for Health and Clinical Excellence, UpToDate, British Medical Journal (BMJ) Best Practice, Joanna Briggs Institute Evidence-Based Health Care Center Database, European Renal Association, National Kidney Foundation, UK Kidney Association, Canadian Society of Nephrology, Japanese Society for Dialysis Therapy, Medlive, Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, VIP, and Wanfang Data and Chinese Biomedical Database. The search period was from database establishment to March 31, 2023. Investigators conducted quality evaluations separately and extracted and summarized evidence based on the theme.Results:A total of 16 articles were included, including five clinical decisions, four guidelines, two evidence summaries, and five expert consensuses. Finally, 15 best pieces of evidence were formed, including four themes of indwelling dialysis catheters, anticoagulation strategies, flushing and sealing techniques, and daily management.Conclusions:Nursing staff should choose the best evidence for preventing thrombosis in hemodialysis catheters based on clinical situations, reduce the occurrence of catheter thrombosis, extend the usage time of catheters, and improve patient outcomes.