177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB). Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115 patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,GeneXpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS). Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%. Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.

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

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

Aim To explore the effect of γ-ray on the mRNA,protein expression levels and metabolic activity level of the key drug metabolic enzyme CYP3A1 in rat liver. Methods Wistar rats were randomly divided into control group, 24 h post-radiation group and 72 h post-radiation group. The experimental group was exposed to total body irradiation of single 6 Gy γ-ray. Blood was collected from the orbital venous plexus for blood routine examination and biochemical analysis 24 h and 72 h after irradiation, and liver tissue was prepared for quantifying expression of CYP3A1 mRNA and liver-specific microRNA (miR-122-5p) through RT-PCR. The expression level of CYP3A1 protein was analyzed by Western blot, and the metabolic activity level of CYP3A1 detected by the specific substrate midazolam combined with LC-MS method. Results Com¬pared with the control group, the weights of the rats in the radiation group significantly decreased, and the number of white blood cells was markedly reduced. Simultaneously, the activities of alanine aminotrans-ferase and alkaline phosphatase continuously descended, as well as the levels of total bilirubin and bile acid significantly increased, which indicated that the liver may be damaged after radiation. The relative expression of CYP3A1 mRNA continued to increase significantly 24 h and 72 h after irradiation. CYP3A1 protein expression and metabolic activity levels showed an obvious increasing trend 24 h after irradiation, and rose significantly 72 h after irradiation compared with the control group. At the same time, the expression of miR-122-5p in liver of rats in the 24 h and 72 h post-radiation group continued to decrease rapidly compared with the control group. Conclusions γ-ray radiation may arouse damage effect on liver, which leads to the continuous up-regulation of the mRNA and protein expression levels of the capital metabolic enzyme CYP3A1 in liver tissue, as well as the elevation of the metabolic activity level. The regulatory mechanism might be related to miR-122-5p.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective: To analyze the classification and functions of cell subsets in laryngeal carcinoma and metastatic lymph nodes, and to explore the evolution trajectory of epithelial cells to tumor cells. Methods: Single-cell RNA sequencing was performed on 5 cases of laryngeal cancer, matched metastatic lymph nodes and 3 normal tissues. Patients were admitted to Ningbo Medical Center Lihuili Hospital from October 22, 2019 to December 16, all patients were male, aged 53-70 years old. Cell subsets of the above-mentioned tissues were analyzed by the Seurat, and the biological functions of cell subpopulation were investigated by functional enrichment analysis. Malignant epithelial cells were identified using copy number variation (CNV). The evolutionary trajectory of epithelial cells to cancer cells was analyzed by cell trajectory analysis, and cancerous transitional cells were identified. The highly expressed genes in transitional cells were analyzed by the FindAllMarker of the Seurat and verified by immunohistochemistry. Results: A total of 66 969 high-quality cells were obtained in 9 major clusters: epithelial cells, T cells, B cells, fibroblasts, endothelial cells, myeloid cells, mast cells, plasmacytoid dendritic cells and nerve cells. The first 5 cell clusters were divided into 8, 6, 4, 3 and 2 subgroups, respectively. Four epithelial cell subsets (C0, C1, C2 and C5) were derived from tumor tissues and metastatic lymph nodes, and had high levels of CNV and tumor cell content. Cell trajectory analysis showed that the evolution trajectory of epithelial cells was from normal epithelial subpopulation C4 to early cancerous cell population C0, which differentiated into three major malignant cell subsets C1, C3, and C5. Epithelial cell C0 may represent the transitional cell population of carcinogenesis, and were enriched in biological processes such as epithelial-mesenchymal transformation and angiogenesis. C0 highly expressed sulforaphane (SFN) which may be related to the occurrence and development of cancer. Immunohistochemistry confirmed that SFN was highly expressed in tumor tissues and metastatic lymph nodes compared with paracancerous tissues. Conclusion: Single-cell sequencing may be used to elucidate the diversity of cells and functions in laryngeal carcinoma tissues and metastatic lymph nodes, and cell population C0 plays a key role in the evolution of cells.
Aged ; Carcinoma, Squamous Cell/pathology* ; DNA Copy Number Variations ; Endothelial Cells/pathology* ; Humans ; Laryngeal Neoplasms/pathology* ; Lymph Nodes/pathology* ; Male ; Middle Aged

OBJECTIVE: To investigate the effect of hydronidone on CCl₄-induced liver fibrosis in rats and explore the possible mechanism. METHODS: Sixty-six male SD rats were randomized into 5 groups, including a control group (n=10), a liver fibrosis model group (n=20), 2 hydronidone dose groups (100 and 250 mg/kg; n=12), and a pirfenidone (250 mg/kg) treatment group (n= 12). Rat models of liver fibrosis were established by subcutaneous injection of CCl₄ in all but the control group. Hydronidone and pirfenidone were given daily at the indicated doses by intragastric administration for 6 weeks. After the treatments, serum samples were collected from the rats for detecting liver function parameters, and hydroxyproline content in the liver tissue was determined. Inflammation and fibrosis in the liver tissue were observed using HE staining and Sirius Red staining. In the cell experiment, human hepatic stellate cell line LX-2 was stimulated with TGF-β1 and treated with hydronidone or pirfenidone, and the expression levels of α-SMA, collagen type I and phosphorylated Smad3, phosphorylated p38, phosphorylated ERK1/2 and phosphorylated Akt were detected with Western blotting. RESULTS: In the rat models of liver fibrosis, treatment with hydronidone obviously improved the liver functions, reduced the content of hydroxyproline in the liver tissue, and significantly alleviated liver fibrosis (P < 0.05). In LX-2 cells, hydronidone dose-dependently decreased the expression levels of α-SMA and collagen type I. In TGF- β1-stimulated cells, the phosphorylation levels of Smad3, P38, ERK, and Akt increased progressively with the extension of the treatment time, but this effect was significantly attenuated by treatment with hydronidone (P < 0.05). CONCLUSION Hydronidone can inhibit the phosphorylation of the proteins in the TGF-β signaling pathway, thereby preventing TGF-β1-mediated activation of hepatic stellate cells, which may be a possible mechanism by which hydronidone alleviates CCl₄-induced liver fibrosis in rats.
Animals ; Male ; Rats ; Carbon Tetrachloride/metabolism* ; Collagen Type I ; Hepatic Stellate Cells/pathology* ; Hydroxyproline/therapeutic use* ; Liver Cirrhosis ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Smad Proteins/metabolism* ; Transforming Growth Factor beta1/metabolism*

Corona virus disease 2019 (COVID-19) is an infec¬tious disease endangering the respirator)' traet and multiple or¬gans of the whole body caused by severe aeute respirator)' syn¬drome coronavirus 2 ( SARS-CoV-2).More than 200 million people in the world have been infected with the disease, which is an unprecedented global plague.Most patients with C0VID-19 only show mild symptoms with a good prognosis, but about 20% of them may develop into severe cases and eause serious compli-cations, including acute respirator)' distress syndrome ( ARDS) , systemic inflammatory response syndrome (SIRS) , cytokine re¬lease syndrome (CRS) , etc.Pyroptosis is a kind of programmed cell death characterized by significant inflammatory response.It is often mediated by inflammatory caspase and the gasdermin family of membrane perforating proteins is the final effector mol¬ecules, resulting in cell membrane swelling and rupture to death, accompanied by the release of a large number of pro-in¬flammatory cytokines (such as IL-lp and IL-18, etc).Pyropto- sis affects the occurrence, progression and treatment of many diseases due to its inflammatory and morphological characteris¬tics, and also plays an important role in severe COVID-19.Therefore, drugs that target key molecules in the pyroapoptotic pathway could he a promising breakthrough for treating severe COVID-19.This article reviews the role of pyroptosis in severe COVID-19 complications ARDS and CHS.