ObjectiveTo investigate the current awareness and optimization recommendations on pneumonia with unknown etiology (PUE) surveillance among Shanghai healthcare professionals, and to provide evidence for the improvement of the surveillance system. MethodsIn December 2024, healthcare professional participants from diverse medical and health institutions were randomly selected within each stratum using a stratified cluster sampling method in all 16 districts of Shanghai for questionnaire surveys on their knowledge and suggestions for optimization of the PUE surveillance system. Descriptive statistics analyses, multivariate logistic regressions, and content analyses were used for data analyses. ResultsA total of 385 survey subjects were involved in the study, including 119 professional staffs from disease prevention and control centers and 266 from medical institutions. Those who understood the case definition for PUE correctly accounted for 67.01% (258/385). Multivariate regression model analyses showed that female gender (aOR=2.22, 95%CI: 1.36‒3.66), professionals from disease control institutions (aOR=2.02, 95%CI: 1.12‒3.72), and those who self-assessed as being familiar with the monitoring system (aOR=2.18, 95%CI:1.23‒3.89) had better understanding of the definition. Overall, 89.61% (345/385) of the survey subjects acknowledged the necessity of the surveillance system. Small number of cases meeting the case definition (54.46%, 214/379), insufficient diagnostic awareness (39.84%, 151/379), and lack of incentives for case reporting (29.29%, 111/379) were major problems for the current surveillance system, with variations observed across different types of institutions. Suggested segments for optimizing the surveillance system included monitoring purpose, case definition, form of monitoring and reporting procedure, organization mechanism, and epidemiological investigation and response. ConclusionThe necessity of PUE surveillance is commonly recognized among healthcare workers. However, the existing system falls short in terms of mastery of case definition and overall surveillance adaptability. There is an urgent need for optimization and improvement to enhance the capacity for preventing and controlling emerging and sudden respiratory infectious diseases.

Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.

Objective:To investigate the correlation between thyroid function and the total cerebral small vessel disease score in the elderly.Methods:This cross-sectional study included elderly people who underwent physical examinations at the Geriatrics Department of Beijing Hospital from April 2019 to December 2020. Participants were devided into 5 groups based on the total score of cerebral small vessel disease: 0, 1, 2, 3, and 4. General clinical data were collected through physical examination reports and outpatient medical records. All participants underwent a 3T brain magnetic resonance imaging (MRI), scan and data were collected to calculate the total cerebral small vessel disease score. Fasting venous blood samples were taken in the morning to measure thyroid hormone levels. Relationships between thyroid hormone levels and lacunar infarcts, microbleeds, white matter hyperintensities (WMH), enlarged perivascular spaces, and total cerebral small vessel disease score were analyzed using Spearman correlation. Multivariate ordinal logistic regression was also used to analyze factors associated with total cerebral small vessel disease score.Results:A total of 545 elderly individuals were included, with a mean age of (75.16±9.18) years, and 505 (92.7%) were male. The number of subjects with a total cerebral small vessel disease score of 0 were 207 (38.0%), 1 were 182 (33.4%), 2 were 99 (18.2%), 3 were 41 (7.5%), and 4 were 16 (2.9%). Statistical significant differences were found in age, fasting blood glucose, systolic blood pressure, triiodothyronine (TT3), free triiodothyronine (FT3), and the proportion of hypertensive patients among the groups (all P<0.05). Spearman correlation analysis showed that TT3 ( r=-0.138, P=0.001) and FT3 ( r=-0.213, P<0.001) were negatively correlated with total cerebral small vessel disease score. Multivariate ordinal logistic regression analysis revealed that age was independently and positively associated with total cerebral small vessel disease score ( OR=1.139, 95% CI: 1.087-1.193, P<0.001), while FT3 was independently and negatively associated with total cerebral small vessel disease score ( OR=0.331, 95% CI: 0.118-0.929, P=0.009). Conclusion:In the elderly population, FT3 levels are independently and negatively associated with total cerebral small vessel disease score.

Objective:To investigate the acute effects of persistent high exposure to atmospheric fine particulate matter (PM 2.5) on residents' outpatient visits for respiratory diseases. Methods:We collected daily outpatient records from 92 hospitals in 13 cities across the Beijing-Tianjin-Hebei region, along with daily PM 2.5, nitrogen dioxide (NO 2), and meteorological data from 2013 to 2018. Five persistent high PM 2.5 exposure scenarios were defined in terms of daily mean PM 2.5 concentrations (>75 μg/m 3 and >150 μg/m 3), duration (≥2 days and ≥3 days), and whether or not there was concurrent exposure to high levels of NO 2 (daily mean NO 2 concentration >50 μg/m 3). A two-stage statistical analysis strategy based on a generalized linear model was applied to conduct a time-series analysis to assess the exposure-response relationship between persistent high PM 2.5 exposure scenarios and residents' outpatient visits for a variety of respiratory diseases, and to estimate excess outpatient visits. Results:During the period, M ( Q1, Q3) PM 2.5 and NO 2 concentrations were 61.2 (42.3, 95.1) μg/m 3 and 40.2 (31.4, 54.4) μg/m 3, respectively, and the daily respiratory disease outpatient visits were 57 (52, 66) cases. When compared with non-permanent high PM 2.5 exposure periods, exposure scenarios with PM 2.5 >75 μg/m 3 and lasting for ≥2 days caused an increased risk of outpatient visits for respiratory diseases by 2.10% (95% CI: 1.44%-2.77%), and resulted in 43 787 (95% CI: 30 025-57 757) excess visits; in this scenario, the concurrent exposure to high levels of NO 2 had a greater acute effect on respiratory disease visits than the absence of exposure to high levels of NO 2 ( P<0.001). The risk of respiratory disease visits increased substantially by 4.41% (95% CI: 3.15%-5.68%) when the daily mean PM 2.5 concentration exceeded 150 μg/m 3 for ≥2 days. Subgroup disease analyses showed that scenarios with daily mean PM 2.5 concentrations exceeding 75 μg/m 3 for ≥3 days caused a significant increase in the risk of lower respiratory tract infections, chronic lower respiratory disease, and asthma visits. Conclusions:Sustained persistent high PM 2.5 exposure increases the risk of outpatient visits for various respiratory diseases; concurrent exposure to high concentrations of NO 2 leads to a greater risk of visiting the clinic, suggesting that the prevention and control of PM 2.5 pollution should be synchronized with the control of mobile source emissions, to synergistically manage the compound pollution of PM 2.5 and NO 2 in the atmosphere.

Objective To optimize the water extraction process of modified Wendan Formula.Methods The comprehensive scores of the content of naringin and neohesperidin as well as the extraction yields of solids were used as the evaluation indexes,the number of decoctions,the decoction time and the solid-liquid ratio as three factors were take into consideration,L9(34)orthogonal experiment was designed to optimize the water extraction process of modified Wendan Formula.Results Combining the orthogonal experiment with the principle of energy conservation and emission reduction in actual production,this study suggests that the optimized process was under the conditions of 1∶8 for the solid-liquid ratio,decoction were performed twice,the first time was 1.5 hours,and the second time was 1 hour.The average composite score of validation of three batches of modified Wendan Formula was 99.00％.Conclusion Such optimized process was stable,feasible and realizable,and it can be applied in water extraction process of modified Wendan Formula.

Objective:To evaluate immunotherapy combined with neoadjuvant chemotherapy before radical total gastrectomy in microsatellite stable locally advanced gastric cancer in two cases.Methods:Two male patients with clinical stage cT3N 1M0 and microsatellite-stable locally advanced gastric cancer were treated with neoadjuvant chemotherapy with PD-1 inhibitor (Nivolumab) combined with SOX (Oxaliplatin+S-1) for 4 cycles before surgery. Standard laparoscopic assisted total gastrectomy with D 2 lymphadenectomy was performed on Feb 2023 and Oct 2023 respectively after the neoadjuvant treatment. Pathological tumor regression grade(TRG) was observed to assess the degree of tumor regression, and follow-up was conducted to monitor tumor markers and abdominal enhanced CT to detect recurrence. Results:Two patients achieved pathological complete response(TRG0). They were followed up until May 2024 and no recurrence was observed.Conclusion:Preoperative combination of chemotherapy and immunotherapy may provide survival benefit for microsatellite stable locally advanced gastric cancer patients.

ObjectiveTo explore the data standard system of electronic medical records in the field of rehabilitation, focusing on the terminology and coding standards, data structure, and key content categories of rehabilitation electronic medical records. MethodsBased on the Administrative Norms for the Application of Electronic Medical Records issued by the National Health Commission of China, the electronic medical record standard architecture issued by the International Organization for Standardization and Health Level Seven (HL7), the framework of the World Health Organization Family of International Classifications (WHO-FICs), Basic Architecture and Data Standards of Electronic Medical Records, Basic Data Set of Electronic Medical Records, and Specifications for Sharing Documents of Electronic Medical Records, the study constructed and organized the data structure, content, and data standards of rehabilitation electronic medical records. ResultsThe data structure of rehabilitation electronic medical records should strictly follow the structure of electronic medical records, including four levels (clinical document, document section, data set and data element) and four major content areas (basic information, diagnostic information, intervention information and cost information). Rehabilitation electronic medical records further integrated information related to rehabilitation needs and characteristics, emphasizing rehabilitation treatment, into clinical information. By fully applying the WHO-FICs reference classifications, rehabilitation electronic medical records could establish a standardized framework, diagnostic criteria, functional description tools, coding tools and terminology index tools for the coding, indexing, functional description, and analysis and interpretation of diseases and health problems. The study elaborated on the data structure and content categories of rehabilitation electronic medical records in four major categories, refined the granularity of reporting rehabilitation content in electronic medical records, and provided detailed data reporting guidance for rehabilitation electronic medical records. ConclusionThe standardization of rehabilitation electronic medical records is significant for improving the quality of rehabilitation medical services and promoting the rehabilitation process of patients. The development of rehabilitation electronic medical records must be based on the national and international standards. Under the general electronic medical records data structure and standards, a rehabilitation electronic medical records data system should be constructed which incorporates core data such as disease diagnosis, functional description and assessment, and rehabilitation interventions. The standardized rehabilitation electronic medical records scheme constructed in this study can support the improvement of standardization of rehabilitation electronic medical records data information.

Objective To establish a rabbit cardiac arrest(CA)model and observe the effect of a TLR4 antagonist on brain injury after cardiopulmonary resuscitation.Methods Seventy-two adult rabbits weighing 2.8-3.3 kg were divided into three groups:sham operation group(Sham group),CA group,and TLR4 an-tagonist group,with 24 rabbits in each group.The Sham group underwent only arterial/venous puncture and tracheal intubation without ventricular fibrillation,CA,or cardiopulmonary resuscitation.The CA group re-ceived equivalent volume of 0.9％sodium chloride solution at the same time points,while the TLR4 antago-nist group received TAK-242 solution(3 mg·kg-1·d-1)immediately,24 h and 48 h after ROSC.The Sham group received 0.9％sodium chloride solution(equivalent volume to the TLR4 antagonist group)immediately after the surgical procedure,and at 24 h and 48 h.Neurological deficit scores(NDS)and plasma neuron-specif-ic enolase(NSE)levels were assessed before CA and at 12 h,24 h,and 72 h after ROSC.Tumor necrosis fac-tor-α(TNF-α)and interleukin(IL)-1β levels in hippocampal tissue were measured using ELISA.TLR4 and nuclear factor-κB(NF-κB)p65 mRNA expression levels were determined by RT-qPCR.Results At 12 h,24 h,and 72 h after ROSC,the neurological deficit scores(NDS)in both the CA group and TLR4 antagonist group were significantly lower than those in the Sham group and their respective pre-CA baselines(all P＜0.05).However,the TLR4 antagonist group showed significantly higher NDS than the CA group at all post-ROSC time points(P＜0.05).Serum neuron-specific enolase(NSE)levels in the CA group and TLR4 antag-onist group were significantly elevated compared to the Sham group and their pre-CA baselines at 12 h,24 h,and 72 h after ROSC(P＜0.05).Notably,the TLR4 antagonist group exhibited significantly lower serum NSE levels than the CA group at all time points(P＜0.05).At 72 h post-ROSC,TNF-α and IL-1β expression levels in both the CA group and TLR4 antagonist group were significantly higher than those in the Sham group(P＜0.05),while the TLR4 antagonist group demonstrated significantly lower TNF-α and IL-1β ex-pression than the CA group(P＜0.05).Additionally,TLR4 and NF-κB p65 mRNA levels in brain tissue were markedly increased in the CA group and TLR4 antagonist group compared to the Sham group at 72 h post-ROSC(P＜0.05).In contrast,the TLR4 antagonist group showed significantly reduced TLR4 and NF-κB p65 mRNA levels compared to the CA group(P＜0.05).Conclusion TLR4 antagonists reduce inflammatory cy-tokine levels in brain tissue and ameliorate brain injury in rabbits after cardiopulmonary resuscitation.

Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5～24.0 kg/m2)and an overweight group(24～<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors