BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

ObjectiveTo investigate the reversal effect of Cordyceps sinensis extract on immunotherapy resistance of non-small cell lung cancer （NSCLC）. MethodsELISA， flow cytometry， and co-culture assays were performed to evaluate the effects of Cordyceps sinensis extract on cytokine secretion， proliferation， and tumor cell killing activity of Jurkat （JKT） cells. Furthermore， the therapeutic effect of Cordyceps sinensis extract on programmed cell death ligand 1 （PD-L1） resistant lung cancer was evaluated through in vivo experiments both alone and in combination with anti-PD-L1 monoclonal antibody. ResultsCordyceps sinensis extract enhanced the secretion of cytokines interferon gamma（IFN-γ）， tumor necrosis factor-alpha（TNF-α） and interleukin-2 （IL-2）in JKT cells， promoted cell proliferation （P=0.006）， and boosted their killing function against tumors （P＜0.001）. Compared with the control group， in vivo study demonstrated that Cordyceps sinensis extract monotherapy effectively inhibited the growth of PD-L1-resistant tumors ［tumor growth inhibition value （TGI）=26.1%， P=0.090］， while its combination with anti-PD-L1 antibody significantly reversed PD-L1 resistance （TGI=50.6%， P＜0.001）. ConclusionThis study provides certain data support for the activation of anti-tumor immunity by Cordyceps sinensis extract， and offers a new treatment strategy for enhancing anti-tumor immunity and reversing immune resistance in lung cancer.

Bitter taste receptors,also known as type 2 taste receptors(T2Rs),are found not only in the mouth's taste bud cells but also in various tissues and cells,including macrophages.Macrophages,known for their re-markable plasticity,play a crucial role in regulating innate immunity,managing inflammation,and orchestrating immune responses to antigens,pathogens,and environmental factors.Recently,the study of the expression and function of bitter taste receptors within macrophages has garnered significant interest.This review summarizes the expression levels and dis-tribution characteristics of bitter taste receptors in macrophages and examines their effects on macrophage polarization,phagocytosis,and chemotaxis,as well as their potential molecular mechanisms.The purpose of this review is to provide in-sight and perspectives for research on the regulatory role of T2Rs in macrophage functions.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

【Objective】 To investigate asymptomatic infection of hepatitis B virus(HBV) among hepatitis B vaccinated donors in Shenzhen, and analyze its serological and molecular characteristics. 【Methods】 The HBsAg ELISA positive blood samples of blood donors born after 1992 were collected. HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were further detected by Roche electrochemiluminescence immunoassay (ECL). BCP/PC and S regions were amplified by Nested-PCRs, HBV DNA quantification were adopted by qPCR simultaneously, and the sequences were also analyzed. 【Results】 A total of 46 632 blood samples of donors(31 612 males and 15 020 females) from December 2020 to January 2022 collected, and 99 samples with HBsAg ELISA positive were screened out. After tested by ECL, Nested-PCRs, and real-time fluorescence PCR, 61 were confirmed HBsAg positive, with the positive rate at 0.13% (61/46 632), including 49 males (0.16%, 49/31 612) and 12 females (0.08%, 12/15 020). The HBsAg positive rate of males was higher than that of females (P<0.05). 50 out of 61 sequences for S region were obtained. By phylogenetic analysis, there were 46 cases of type B (92%, 46/50, 38 males and 8 females), 4 cases of type C (8%, 4/50, 3 males and 1 female). The high frequency mutations observed in S region were N40S (8/46,17.39%), G44E (7/46,15.22%), Q129H/R(6/46,13.04%), Y161F/S(7/46, 15.22%), V179A(4/46,8.70%), S53L(2/4,50%), C69T(2/4,50%) and I126S/T(2/4,50%), including the immune escape mutations Q129R and T/I126A/N/S/T. 【Conclusion】 Hepatitis B vaccination can significantly reduce the positive rate of HBsAg and increase the safety of blood transfusion. The high frequency immune escape mutations have become a potential risk of blood safety, and need to be further explored.

Background Perfluorinated and polyfluoroalkyl substances (PFAS), a large group of emerging pollutants, are ubiquitous in the ecological environment. Their multiple organ toxic effects on human body are reported. Understanding the exposure level of PFAS in cord serum and associated influencing factors can provide scientific evidence for studying maternal and newborn health effects and risk regulation. Objective To explore the exposure levels of PFAS in cord serum and potential impact factors. Methods This study was based on the maternal and infant database and the cord serum sample bank of the Sheyang Mini Birth Cohort Study (SMBCS) established in 2009. A self-designed questionnaire was used to collect information on sociodemographic characteristics, living environment, and lifestyle of mothers during pregnancy. A total of 1097 cord serum samples were measured utilizing ultra-high performance liquid chromatography-Q-Exactive Orbitrap high-resolution mass spectrometry. Multiple linear regression models were used to identify influencing factors related to PFAS exposure level in cord serum. Results A total of 38 types of PFAS were detected in the cord serum samples, including 20 perfluorocarboxylic acids (PFCA), 14 perfluorosulfonic acids (PFSA), and 4 other types of PFAS. The detection rates of 14 PFAS compounds were above 50%. The detection rates of perfluoro-1-hexanesulfonic acid (PFHxS), perfluoro-1-octanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA) were in the range of 99.18%-100.00%. The median concentrations of PFOA and 6∶2 chlorinated polyfluorinated ether sulfonic acid (6∶2CI-PFESA) were higher than those of the other compounds, which were 3.76 µg·L⁻¹ and 2.61 µg·L⁻¹, respectively. The correlation coefficients among cord serum PFAS were in the wide range of 0.0911-0.8429 (P < 0.05). The associations between PFHxS and perfluoro-1-heptanesulfonic acid (PFHpS) (r=0.8429, P < 0.05), PFOS and PFHpS (r=0.7012, P < 0.05), and PFUdA and perfluorododecanoic acid (PFDoA) (r=0.7875, P < 0.05) were positive. The proportions of PFCA and PFSA in the cord serum samples were 60.1% and 38.4%, respectively. PFOA and 6∶2 Cl-PFESA were the predominant compounds in the cord serum samples, whose proportions were 37.8% and 19.3%, respectively. The concentrations of specific types of cord serum PFAS had varied associations with the following demographic variables of pregnant women: age, parity, education level, gestational age, and occupation. The multiple linear regression analysis found that the concentrations of 8 PFAS (PFHxS, PFHpS, PFNA, PFOS, PFDA, PFUdA, PFDoA, and 6∶2 CI-PFESA) in umbilical cord serum were lower in pregnant women aged 25 years and older than in those under the age of 25 years; compared to pregnant women with education levels at or below junior middle school, those with education levels at or above high school had lower concentrations of perfluoroheptanoic acid (PFHpA); the concentration of PFHpA in cord serum was negatively correlated with household annual income; multiparous women had higher concentrations of PFNA, PFUdA, and PFDoA than primiparous women; compared to mothers engaged in manual labor, the concentration of perfluoro-1-butanesulfonic acid (PFBS) in umbilical cord serum was lower in mothers engaged in mental labor, while the concentrations of PFBS and PFOA were lower and the concentrations of perfluorotridecanoic acid (PFTrDA) and 8∶2 chlorinated polyfluorinated ether sulfonic acid (8∶2CI-PFESA) were higher in mothers of other occupational types; the concentrations of umbilical cord serum PFOA, PFOS, PFUdA, and PFDoA were positively correlated with the gestational age of pregnant women, while N-methylperfluoro-1-octanesulfonamido acetic acid (N-MeFOSAA) was negatively correlated with the gestational age of pregnant women; PFTrDA was negatively correlated with the birth weight of newborns; compared with those with insufficient gestational weight gain, those with adequate gestational weight gain had lower PFDoA, while those with excess gestational weight gain had higher N-MeFOSAA. Conclusion PFAS compounds exposure is common in the mothers and infants in the study area. PFOA and 6∶2 CI-PFESA are the two main compounds in cord serum. Cord serum PFAS are associated with several demographic characteristics of the pregnant women. Future research needs to pay more attention to PFAS alternatives and other emerging contaminants.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.

Objective:To investigate the relationship between serum estradiol(E2)levels on the day before transcervical resection of adhesion(TCRA)and pregnancy outcomes in moderate-severe intrauterine adhesion(IUA).Methods:Clinical data of patients with moderate-severe IUA diagnosed and received TCRA in the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2019 were extracted and ana-lyzed.The primary outcome indicator was the pregnancy rate during the 12-month follow-up period.Multiple re-gression analysis,smoothed curve fitting and recursive algorithm analysis were applied in this study.Results:A-mong the 288 patients who met the inclusion criteria,222 met the criteria and were finally included in the analysis.The results of multiple regression analysis showed that the E 2 level on the day before surgery was negatively cor-related with the pregnancy rate after TCRA(aOR 0.77,95% CI 0.63-0.93,P=0.0074).Recursive algorithm a-nalysis showed that when the preoperative serum E2 level was less than 380.6 pmol/L,for every increase of 36.7 pmol/L pregnancy rate decreased by approximately 20% (aOR 0.78,95% CI 0.67-0.89,P=0.0004).Conclusions:The results suggest that preoperative serum E2 levels are negatively associated with pregnancy outcomes in patients with moderate-to-severe IUA.