BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

The aim of this study is to investigate the molecular mechanism of licochalcone A (LCA) in alleviating abnormal gluconeogenesis and endoplasmic reticulum (ER) stress caused by type 2 diabetes mellitus (T2DM). In the in vivo study, 8-week-old male C57BL/6J mice were fed with a high-fat and high-sugar diet and injected intraperitoneally with streptozotocin (STZ) to establish a T2DM model. LCA (5 and 10 mg·kg^-1) was administered at an interval of 3 days for 3 weeks with metformin (MET, 200 mg·kg^-1) as a positive control drug. The animal experiment protocol was reviewed and approved by the Experimental Animal Ethics Committee of Beijing University of Chinese Medicine (approval number: BUCM-4-2021061701-2060). Human hepatoma cell line HepG2 was used as the experimental cell line for in vitro experiments. Sodium palmitate (SP) was used to induce the insulin resistance cell model and tunicamycin (TM) was applied to establish the ER stress cell model. Real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) were used to detect the mRNA and protein levels of gluconeogenesis and ER stress-related targets, respectively. Molecular docking and dynamics simulations were used to verify the interaction between LCA and key targets. The results showed that LCA inhibits gluconeogenesis by reducing phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6P) and increasing 6-phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) at both the mRNA and protein levels, as well as suppressing the activity of pyruvate carboxylase (PC). Additionally, LCA alleviates ER stress by downregulating the transcription of eukaryotic initiation factor 2 subunit α (eIF2α), inositol-requiring enzyme 1α (IRE1α), X-box binding protein 1 (XBP1), c-Jun N-terminal kinase 1 (JNK1), and activating transcription factor 6α (ATF6α), inhibiting the transcription and protein expression of glucose-regulated protein 78 (GRP78), and suppressing the phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK). In conclusion, LCA alleviates abnormal gluconeogenesis and ER stress, thereby ameliorating the abnormal metabolism induced by T2DM.

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.
Rats ; Animals ; Chromatography, Liquid ; Gardenia ; Tandem Mass Spectrometry ; Gastrointestinal Microbiome ; alpha-Linolenic Acid ; Metabolomics/methods* ; Arthritis, Rheumatoid/drug therapy* ; Inflammation ; Glycerophospholipids

The formulation and revision of the detection methods of indoor air quality standards is an important, rigorous and delicate endeavor. This paper introduced the formulation and revision of the detection methods of the standards for indoor air quality (GB/T 18883-2022), focusing on the revision process, revision principles, main adjustments and technical points of some key indicators to facilitate users to better understand and apply the detection methods in standards for indoor air quality (GB/T 18883-2022).
Humans ; Air Pollution, Indoor ; China ; Reference Standards ; Air Pollutants/analysis*

The formulation and revision of the detection methods of indoor air quality standards is an important, rigorous and delicate endeavor. This paper introduced the formulation and revision of the detection methods of the standards for indoor air quality (GB/T 18883-2022), focusing on the revision process, revision principles, main adjustments and technical points of some key indicators to facilitate users to better understand and apply the detection methods in standards for indoor air quality (GB/T 18883-2022).
Humans ; Air Pollution, Indoor ; China ; Reference Standards ; Air Pollutants/analysis*

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective:To construct a clinical prediction model for early postoperative parastomal hernia in patients with enterostomy and to conduct internal and external validation and evaluation of clinical benefit.Methods:A total of 1 071 patients with enterostomy treated in Zhongshan Hospital Affiliated to Fudan University from October 2013 to December 2020 were selected as the research objects by the convenient sampling method. Patients from October 2013 to December 2019 were selected as the modeling group ( n=943) . The data of patients were obtained by questionnaire and other methods. The clinical prediction model of early postoperative parastomal hernia in patients with enterostomy was constructed based on Cox regression analysis and the model was internally verified by Bootstrap method. Patients from January to December 2020 were selected as the validation group ( n=128) for external validation of the model. C-statistic, area under receiver operating characteristic curve and calibration map were used to evaluate the discrimination and calibration of the model. Decision curve analysis was used to draw decision curve analysis chart to evaluate the clinical benefit of the prediction model. Results:Age, history of alcohol consumption, postoperative body mass index, diabetes mellitus, respiratory diseases, history of abdominal surgery, stoma route, stoma nature and C-reactive protein were independent influencing factors for early postoperative parastomal hernia in patients with enterostomy ( P<0.05) . The C- index value of early postoperative nomogram was 0.710 (95% CI: 0.660-0.750) . Conclusions:The clinical prediction model of early parastomal hernia in patients with enterostomy has good predictive performance, which can help clinical medical staff to screen out high-risk groups in time and guide medical staff to focus on prevention.

Objective:To construct a clinical prediction model for early postoperative parastomal hernia in patients with enterostomy and to conduct internal and external validation and evaluation of clinical benefit.Methods:A total of 1 071 patients with enterostomy treated in Zhongshan Hospital Affiliated to Fudan University from October 2013 to December 2020 were selected as the research objects by the convenient sampling method. Patients from October 2013 to December 2019 were selected as the modeling group ( n=943) . The data of patients were obtained by questionnaire and other methods. The clinical prediction model of early postoperative parastomal hernia in patients with enterostomy was constructed based on Cox regression analysis and the model was internally verified by Bootstrap method. Patients from January to December 2020 were selected as the validation group ( n=128) for external validation of the model. C-statistic, area under receiver operating characteristic curve and calibration map were used to evaluate the discrimination and calibration of the model. Decision curve analysis was used to draw decision curve analysis chart to evaluate the clinical benefit of the prediction model. Results:Age, history of alcohol consumption, postoperative body mass index, diabetes mellitus, respiratory diseases, history of abdominal surgery, stoma route, stoma nature and C-reactive protein were independent influencing factors for early postoperative parastomal hernia in patients with enterostomy ( P<0.05) . The C- index value of early postoperative nomogram was 0.710 (95% CI: 0.660-0.750) . Conclusions:The clinical prediction model of early parastomal hernia in patients with enterostomy has good predictive performance, which can help clinical medical staff to screen out high-risk groups in time and guide medical staff to focus on prevention.

The reconstruction of tactile function during the repair of skin damage caused by factors including burns is inseparable from the functional regeneration of tactile receptor Merkel cells. Merkel cells mainly exist in the basal layer of the epidermis and are closely connected with nerves to form Merkel cell-nerve complexes, which play an important role in biological organisms. A large number of studies have shown that Merkel cells conduct precise transmission of mechanical force stimuli through the mechanically gated ion channels PIEZO2, and perform the function of tactile receptors. In this paper, we discussed the characteristics of Merkel cells and analyzed the different subgroups that may possibly exist in this type of cells and their functions, at the same time, we investigated the animal model research of touch-related diseases and the clinical diseases related to touch, revealing the importance of Merkel cell function research.
Animals ; Ion Channels/metabolism* ; Mechanotransduction, Cellular/physiology* ; Merkel Cells/physiology* ; Skin/metabolism* ; Touch/physiology*