Background A diverse cohort of patients and susceptible individuals congregate in healthcare facilities, where exposure to pathogenic microorganisms associated with respiratory infectious diseases constitutes a significant risk factor for cross-infection. Central air-conditioning ventilation systems improve some indoor environment indicators while exacerbating the risk of transmission of respiratory infectious diseases. Objective To investigate the distribution characteristics of microbial communities in the central air-conditioning ventilation systems of hospitals, providing a scientific basis for the selection of microbial indicators in hygiene standards for hospital central air-conditioning ventilation systems and for hospital risk early warning systems. Methods In October 2023, two central air-conditioning ventilation systems were selected from a Grade 3A hospital in Shanghai: one was an all-air air-conditioning system serving the waiting area on the ground floor, and the other was a fan coil plus fresh air system serving the outpatient area on the third floor. Samples from four different components of the ventilation systems—air outlets, filters, surface coolers, and condensate trays—were collected for high-throughput sequencing of the 16S rRNA gene to analyze bacterial communities. Alpha-diversity and beta-diversity analyses were performed to investigate the microbial community composition and diversity characteristics of the hospital central air-conditioning ventilation systems. Functional analysis was conducted to determine the relative abundance of bacterial functions in these systems.Results A total of 528 operational taxonomic units (OTUs) were identified, encompassing 20 bacterial phyla, 37 classes, 79 orders, 123 families, and 240 genera. The analysis revealed that the bacterial community was predominantly composed of Proteobacteria, Gemmatimonadates, Bacteroidetes, and Actinobacteria. The diversity analysis indicated that bacterial community richness and diversity were highest in the condensate trays, while no statistically significant differences (P > 0.05) were observed in the bacterial community composition among the air outlets, filters, and surface coolers. The functional analysis showed that the bacterial communities in the central air-conditioning ventilation systems primarily exhibited chemoheterotrophic, oxidative energy-dependent heterotrophic, and ureolytic functional characteristics. Conclusion The dominance of Proteobacteria suggests that this phylum exhibits strong adaptability in the central air-conditioning ventilation systems, possibly related to its ability to survive and reproduce under varying environmental conditions. The diversity analysis indicates that the condensate tray is a critical area for bacterial proliferation in the central air-conditioning ventilation systems. The similarity in environmental conditions among the air outlets, filters, and surface coolers result in similar bacterial community structures. The functional analysis reveals that the bacterial communities possess robust energy conversion and metabolic capabilities, potentially contributing to processes such as organic matter decomposition and nitrogen cycling within the central air-conditioning ventilation systems.

convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.

Bipolar disorder with mixed features is currently a prevalent clinical phenomenon,with patients exhibiting a heightened risk of suicidal behaviour,suboptimal therapeutic outcomes,poor prognostic indicators and frequently accompanied by significant impairment in psychosocial functioning.The current body of research on the pathological mechanisms of bipolar disorder with mixed features has proposed several mechanisms including neurotransmitter imbalance leading to abnormal emotion regulation,hypothalamic-pituitary-adrenal(HPA)dysfunction triggering an excessive stress response,circadian rhythm disorder affecting the sleep pattern,abnormal functional connectivity of the cerebral cortex and limbic system,independent and multidirectional changes in four dimensions,such as behaviour,cognition,mood,and sleep.Further studies are required to integrate the results of neurobiology,imaging,genetics and other multidisciplinary fields in order to provide more precise targets for the diagnosis and treatment of bipolar disorder with mixed features.

Objective:To explore the feasibility and rationality of lobectomy in the treatment of pediatric thyroid papillary carcinoma (PTC) with low-intermediate risk.Methods:The clinicopathological features and follow-up data of pediatric PTC with low-intermediate risk were reviewed from March 2000 to December 2018 in Cancer Hospital of Chinese Academy of Medical Sciences. The correlations between different surgical procedures and prognoses were evaluated. Propensity score matching(PSM) was used to adjust for risk factors, and the difference in prognoses between the total thyroidectomy (TT) group and the lobectomy (LT) group was compared.Results:A total of 140 patients were included in the study, including 36 males and 104 females. The age range was from 6-year-old to 18-year-old. There were 43 low-risk patients and 97 intermediate-risk patients. The median follow-up time was 87.5 months, ranging from 8 to 241 months, and 20 patients (14.3%) showed recurrence during the follow-up period. Univariate analysis showed that N1b, extrathyroidal extension, the number of lymph node metastasis>5, the ratio of lymph node metastasis≥0.19, and radioactive iodine treatment were risk factors for recurrence (all P value below 0.05), but multivariate analysis showed that only the ratio of lymph node metastasis≥0.19 ( HR=8.69, 95% CI=1.08-70.21, P=0.043) was an independent risk factor for recurrence. There was no significant difference in the 5-year recurrence free survival rates between TT group and LT group before propensity score matching (82.8% vs. 86.5%, χ 2=0.219, P=0.640) and after propensity score matching (89.6% vs. 90.4%, χ 2=0.099, P=0.753). Conclusion:There is no significant difference in recurrence-free survival between TT group and LT group. Lobectomy is feasible for selective pediatric PTC with low-intermediate risk.

We reported a case of polyglandular syndrome induced by programmed death-1(PD-1) inhibitors. The patient was a 51-years-old male with non-small cell lung cancer, treated with PD-1 inhibitor nivolumab/pembrolizumab because of postoperative subcarinal lymph node metastasis indicated by PET-CT. During 14 cycles of PD-1 inhibitor treatment, the patient successively developed primary hypothyroidism, and type 1 diabetes mellitus(T1DM). More than five months after the withdrawal of pembrolizumab, the patient experienced recurrentce. Laboratory examinations showed mild hyponatremia and hypopituitarism including ACTH and growth hormone(GH)/insulin-like growth factor-1(IGF-1) insufficiency. This is the first report of a patient diagnosed as polyglandular syndrome caused by PD-1 inhibitor. In particularly, the hypothyroidism and T1DM did not improve after drug withdrawal, while hypopituitarism was further aggravated. This case reminds us that we should pay more attention to the changes of endocrine function during and after the treatment of PD-1 inhibitor, so that we can make the correct diagnosis and take proper medical measures timely, to avoide missed diagnosis, and improper treatment.

To investigate the relationship of both DNA methylation level and methylenetrahydrofolate reductase(MTHFR)gene polymorphism with ankylosing spondylitis(AS). Totally 200 Chinese AS patients with HLA-B27(+)and 120 healthy controls were included from Hunan Province.All the cases were diagnosed according to the 1984 modified New York criteria for AS.The DNA methylation was examined by cytosine extension method,while the MTHFR gene C677T polymorphism was analyzed by the polymerase chain reaction(PCR)and restriction fragment length polymorphism(RFLP).The plasma homocysteine(Hcy)level was examined by enzyme-linked immunosorbent assay(ELISA),while the red blood folate level was analyzed by the specific immunoassays. The ratio of the T/T genotype mutation in the AS group was significantly higher than in the control group(17.0% 5.0%;=9.874, =0.002).The plasma homocysteine concentration of AS group was(18.71 ± 2.42)μmol/L,which was significantly higher than that in normal control group [(10.97 ± 2.93)μmol/L](=24.402, <0.001).The plasma Hcy concentration of the T/T genotype [(21.70±1.80)μmol/L] was significantly higher than that of the C/C genotype[(18.31±1.94)μmol/L](=12.088, =0.01)and the C/T genotype [(17.80±2.18)μmol/L](=6.496, =0.01)in the AS group.The DNA methylation level of the T/T genotype in AS group was significantly lower than that in normal control group(=5.655, <0.001)and also significantly lower than those of the C/C genotype(=11.514, <0.001)and the C/T genotype in AS group(=10.287, <0.001). In the Han population in Hunan Province,the C677T polymorphism of the MTHFR gene is associated with the onset of AS.The T/T mutation at position 677 of the MTHFR gene is an important influencing factor for hyperhcyemia in the AS patients.The T/T mutation at position 677 of the MTHFR gene is associated with genomic DNA hypomethylation.Thus,hypomethylation of DNA may be one of the pathogenic mechanisms of AS.
DNA ; DNA Methylation ; Genomics ; Genotype ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; Polymorphism, Genetic ; Spondylitis, Ankylosing

In the past ten years, the research and application of microbiome has continued to increase. The microbiome has gradually become the research focus in the fields of life science, environmental science, and medicine. Meanwhile, many countries and organizations around the world are launching their own microbiome projects and conducting a multi-faceted layout, striving to gain a strategic position in this promising field. In addition, whether it is scientific research or industrial applications, there has been a climax of research and a wave of investment and financing, accordingly, products and services related to the microbiome are constantly emerging. However, due to the rapid development of microbiome sequencing and analysis related technologies and methods, the research and application from various countries have not yet unified on the standards of technology, programs, and data. Domestic industry participants also have insufficient understanding of the microbiome. New methods, technologies, and theories have not yet been fully accepted and used. In addition, some of the existing standards and guidelines are too general with poor practicality. This not only causes obstacles in the integration of scientific research data and waste of resources, but also gives related companies unfair competition opportunity. More importantly, China still lacks national standards related to the microbiome, and the national microbiome project is still in the process of preparation. In this context, the experts and practitioners of the microbiome worked together and developed the consensus of experts. It can not only guide domestic scientific research and industrial institutions to regulate the production, learning and research of the microbiome, the application can also provide reference technical basis for the relevant national functional departments, protect the scale and standardized corporate company's interests, strengthen industry self-discipline, avoid unregulated enterprises from disrupting the market, and ultimately promote the benign development of microbiome-related industries.
China ; Consensus ; Humans ; Industry ; Microbiota

Objective:To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).Methods:Twelve patients with severe refractory RA were treated with tocilizumab.The clinical and laboratory indices and the side effects were recorded after treatment.Results:The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients,which were significantly improved after TCZ therapy (P＜0.05),and no obvious adverse reactions were found.Conclusion:Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.

Objective To observe the effect of qixiantang decoction on asthma model mice and to explore its mechanism of phosphatase gene ( PTEN)-up-regulation. Methods A total of 28 healthy female BALB/c mice were divided into 4 groups according to the random number table ( n=7 ): normal control group, model control group, qixiantang decoction group, and dexamethasone group. The mice were sensitized with ovalbumin ( OVA) for asthma model. Qixiantang decoction group was treated with drug after OVA sensitization. Hematoxylin-eosin ( H-E) staining was applied to observe the pulmonary inflammation in mice, and periodic acid Schiff ( PAS) staining was used to examine airway mucus secretion. ELISA was used to detect the concentration of serum IgE. Real-time quantitative PCR was used to examine IL-13 and IL-5 gene expression changes in lung tissues of mice. Western blotting was used to detect the expression of PTEN and SIRT1 protein in lung tissues. Results The lung tissue inflammatory infiltration and mucus secretion in model control group were higher than normal control group (P<0. 01), and that in the qixiantang decoction group. The level of serum IgE in model control group [(6. 67 ± 2. 59) pg·mL-1)] was significantly higher than normal control group [(0.27 ± 0.05) pg·mL-1, P <0.01] ,and that in the qixiantang decoction group [(3.52 ±1.44) pg·mL-1,P<0.05]. The expression of PTEN and SIRT1 in lung tissue of model control group were significantly lower than normal control group, and that of qixiantang decoction group. The expression of IL-5 and IL-13 mRNA of qixiantang decoction group was significantly lower (P<0. 05). Conclusion Qixiantang decoction could significantly ameliorate inflammation in asthmatic mice by regulate IgE、IL-5、IL-13 expression, and might up-regulate PTEN expression via SIRT1 signal.