BACKGROUND:Successful uterine spiral artery remodeling is necessary for normal pregnancy,in which vascular smooth muscle cells are important cells.Interferon-γ is associated with the loss of vascular smooth muscle cells during early pregnancy.However,the specific mechanism is not fully understood. OBJECTIVE:To investigate the effects of interferon-γ on migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway. METHODS:Human vascular smooth muscle cells were divided into control group and interferon-γ group.The control group was cultured normally,and the interferon-γ group was treated with 10 ng/mL interferon-γ for 24 hours.The migration ability of vascular smooth muscle cells was detected by Transwell assay.The apoptosis of vascular smooth muscle cells was detected by TUNEL assay and flow cytometry.The mRNA expression levels of NLRP3 and caspase-1 were detected by qPCR.Western blot assay was utilized to detect NLRP3,caspase-1,and cleaved N-terminal GSDMD protein expression levels. RESULTS AND CONCLUSION:Compared with the control group,the migration ability and apoptosis rate of vascular smooth muscle cells in interferon-γ group were significantly increased(P<0.05).Compared with the control group,the mRNA expression levels of NLRP3 and caspase-1 in vascular smooth muscle cells of interferon-γ group were significantly increased(P<0.05).Compared with control group,the expression levels of NLRP3,caspase-1,and cleaved N-terminal GSDMD protein in vascular smooth muscle cells in the interferon-γ group were significantly increased(P<0.05).The results suggest that interferon-γ may regulate the migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway.

OBJECTIVE To investigate the improvement effect and mechanism of desloratadine citrate disodium in mice with hypersensitivity pneumonitis （HP）. METHODS Sixty mice were randomly divided into blank control group （normal saline）， model group （normal saline）， prednisone group （positive control， 20 mg/kg） and desloratadine citrate disodium low-， medium- and high-dose groups （0.5， 1， 2 mg/kg）， with 10 mice in each group. Except for the blank control group， mice in other groups were intraperitoneally injected with ovalbumin （OVA） and exposed to OVA inhalation to establish the HP model. On day 22 post- modeling， mice in each group were administered the corresponding drugs or normal saline， once a day， for 11 consecutive days. After the last administration， lung function and airway hyperreactivity were assessed. The levels of interleukin-1β （IL-1β）， IL-4 and IL-6 in serum as well as the levels of IL-8， IL-13 and IL-17A in bronchoalveolar lavage fluid were determined. Pathological changes in lung tissue of mice were evaluated using Masson staining. Furthermore， the expressions of fibrosis-related proteins， including transforming growth factor β1 （TGF-β1）， type Ⅲ collagen （Col-Ⅲ） and fibronectin （FN） were determined in lung tissues. RESULTS Compared with the blank control group， the model group showed significant deterioration in lung function （P＜ 0.01）， while airway resistance and serum levels of IL-1β， IL-4， IL-6 and the levels of IL-8， IL-13 and IL-17A in the bronchoalveolar lavage fluid were increased significantly （P＜0.01）. The lung tissues exhibited alveolar collapse， atrophy， and structural disarray， along with the formation of extensive deposits of blue collagen fibers， the percentage of positive staining increased significantly （P＜0.01）. Additionally， the expression levels of TGF-β1， Col-Ⅲ， and FN proteins in the lung tissues were also increased significantly （P＜0.01）. After intervention with desloratadine citrate disodium， the pathological changes in the lung tissues of mice in each dosage group of desloratadine citrate disodium showed varying degrees of improvement， and most of the aforementioned indicator levels were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Desloratadine citrate disodium can improve the lung function and airway hyperreactivity of HP mice， inhibit the release of inflammatory factors in serum and bronchoalveolar lavage fluid， and reduce the deposition of collagen fibers. Its mechanism of action may be related to anti-inflammatory， immunomodulatory， and antifibrotic effects.

Objective:To analyze the specific immunoglobulin G (IgG) antibodies level in the population after the coronavirus disease 2019 (COVID-19) pandemic in Henan Province.Methods:A total of 5 178 peripheral venous blood samples were collected from 10 districts (counties) in Henan Province according to the national seroepidemiological survey program for COVID-19, and the method of cluster random sampling was adopted from March 6 to 15, 2023. Descriptive analysis was used for the basic data, history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, SARS-CoV-2 infection of the respondents. The specific IgG antibody of SARS-CoV-2 was detected using chemiluminescence method. Statistical analysis was performed by using rank sum test, Kruskal Wallis test, and Dunn′s test.Results:The overall positive rate of SARS-CoV-2-specific IgG antibody was 83.35%(4 316/5 178). There were statistically significant differences in the specific IgG antibodies against SARS-CoV-2 produced by people of different sexes, different ages, infected or not, vaccinated or not, and vaccinated with different doses of SARS-CoV-2 vaccine ( Z=3.60, H=195.32, Z=6.10, 18.08, H=382.70, respectively, all P<0.001). The specific IgG antibodies produced by unvaccinated+ uninfected group, unvaccinated+ infected group, vaccinated+ uninfected group, and vaccinated+ infected group were 3.54(0.98, 11.00), 60.65(2.33, 84.80), 133.00(59.80, 173.00), and 142.00(98.30, 176.00), respectively. And the difference was statistically significant( H=354.62, P<0.001). The specific IgG antibodies of uninfected people increased with the increase of inoculum times( H=287.00 and 98.48, both P<0.001). The specific IgG antibodies of people who were not infected with SARS-CoV-2 in the groups of whose interval from the last inoculation of SARS-CoV-2 vaccine to blood collection was less than three months, three to six months and more than six months were 171.86(156.04, 196.57), 71.71(17.08, 110.38) and 132.14(57.59, 172.25), respectively, and the difference was statistically significant ( H=19.93, P<0.001). Among them, the absolute difference between the less than three months group and the three to six months group was statistically significant ( Z=3.67, P<0.001), and the absolute difference between the less than three months group and the more than six months group was statistically significant ( Z=3.47, P<0.001). The specific IgG antibodies level in the less than three months group was the highest. Conclusions:There is a certain correlation between the number of SARS-CoV-2 vaccine doses and the specific IgG antibodies level in uninfected people. The specific IgG antibodies could maintain a high level for three months after immunization.

Secondary caries is one of the main reasons that affect the service life of the restoration. Compared with primary caries, secondary caries have some particularities in etiology, disease progression, clinical manifestation, clinical diagnosis, treatment and prevention. Starting from the above aspects, combined with the latest basic and clinical research on secondary caries, this paper summarizes and analyzes its pathogenesis and prevention strategies, which will lay a certain foundation for in-depth understanding of secondary caries and promoting its clinical prevention and treatment.

Objective: To investigate the rifampicin resistance status and its influencing factors among elderly patients with pulmonary tuberculosis in Changzhou City, Jiangsu Province, so as to provide the basis for improving drug-resistant pulmonary tuberculosis prevention and control strategies. Methods: Patients aged over 60 years with pulmonary tuberculosis treated in tuberculosis designated hospital was selected. Demographic information, history of previous disease, history of diagnosis and treatment and drug sensitivity test were collected. Rifampicin resistance among elderly patients with pulmonary tuberculosis and its influencing factors was analyzed. Results: Totally 249 elderly patients with pulmonary tuberculosis were included, with an average of (69.75±4.36) years. There were 147 males and 102 females, with a gender ratio of 1.44∶1. There were 183 treatment-naïve patients (73.49%) and 66 retreated patients (26.51%). Rifampicin resistance was found in 21 cases, with a drug resistance rate of 8.43%. Among them, there were 7 treatment-naïve patients (3.83%), and 14 retreated patients (21.21%). Multivariable logistic regression analysis showed that retreated elderly patients with pulmonary tuberculosis had a higher risk of rifampicin resistance (OR=10.551, 95%CI: 1.344-82.857). Conclusion The rifampicin resistance rate of 249 elderly patients with pulmonary tuberculosis was 8.43% and was associated with the type of treatment.

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

Objective : To investigate the partial mechanism and effect of transplanting with human umbilical cordderived mesenchymal stem cells (hUC⁃MSCs) to repair articular cartilage defects in a rat model. Methods : Critical⁃sized osteochondral defects were created in the trochlear grooves of rat femurs. The hUC⁃MSCs were transplanted into the defect of experimental knees. Sham group and model group knees were transplanted with saline. The effects of articular cartilage repair were evaluated at 10 weeks after surgery with International Cartilage Repair Society (ICRS) repair score , histological examination and immunohistochemical analysis. The effects of hUC⁃MSCs on the proliferation and migration of chondrocytes were detected by Transwell in vitro. Results : After transplanting with hUC⁃MSCs , the articular surfaces of the defect sites were changed smoother thanthose of the model group , and the cellular morphology and arrangement were also improved in Safranin O staining or Masson staining results. Similar to surrounding normal articular cartilage tissue after treatment for 10 weeks , and the ICRS repair score was signifision of type Ⅱ (Col Ⅱ ) collagen and decrease the level of type Ⅰ collagen( Col Ⅰ ) in the articular defect site. Meanwhile , the increased protein expression of SOX9 and protein transportation to the nucleus were observed after treatment with hUC⁃MSCs for 10 weeks. In vitro , chondrocytes could be proliferated and migrated after co⁃cultured with hUC⁃MSCs. Conclusion Transplanting with hUC⁃MSCs can promote cartilage repair, and its role maybe related to the protection of the cartilage matrix and the promotion of chondrocyte proliferation and migration.

Objective : To study the protective effect and mechanism of iPSC⁃MSCs on cartilage matrix in knee oste⁃ oarthritis (KOA) patients in vitro. Methods : Cartilage tissues removed from KOA patients with joint replacement surgery were collected and subjected to tissue and cellular experiments , respectively. Cartilage tissue was cut into small pieces and randomly divided into a control group , an IL⁃1β ( 10 ng/ml) induction group , and iPSC⁃MSCs 96 h and then co⁃cultured with different amounts of iPSC⁃MSCs ( 1 × 104 , 1 × 105 , 1 × 106 ) cells for 72 h. For in tissues , the pathological changes of isolated cartilage tissues were examined by HE staining. The levels of ADAMTS⁃4 , ADAMTS⁃5 , and type II collagen expression were analyzed by immunohistochemistry , while the levels of MMP13 , IL⁃6 , and IL⁃10 in culture supernatants were detected by ELISA kits. The 2 to 5 generations of chondrocytes , which were extracted from cartilage tissue of KOA patients , were stimulated with IL⁃1β ( 10 ng/ml) for 48 h and then co⁃cultured with different concentrations of iPSC⁃MSCs ( 1 × 104 , 1 × 105 , 1 × 106 ) cells for 72 h. Immunofluorescence and Western blot detected the expression of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 in chondrocytes. Results : Comparison with the control group , in the IL⁃1β⁃induced group , the levels of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 increased , the level of type II collagen decreased , the levels of MMP⁃13 and IL⁃6 in the culture supernatant increased ( P < 0. 05) , and the level of IL⁃10 decreased ( P < 0. 05) ; Compared with the IL⁃1β⁃induced decreased the expression of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 , promoted type II collagen expression and elevated IL⁃10 levels. Conclusion iPSC⁃MSCs inhibited ADAMTS⁃4 and ADAMTS⁃5 expression in vitro , reduced cartilage extracellular matrix degradation , and played a role in articular cartilage protection.

Objective: To establish and evaluate the pyroptosis model of rat chondrocytes induced by tumor necrosis factor-α(TNF-α). Methods: A two-step enzymatic digestion method was used to obtain rat articular chondrocytes, inverted phase contrast microscope was used to observe the morphological structure of chondrocytes. Toluidine blue staining and type Ⅱ collagen(Col Ⅱ) staining were used to identify chondrocytes. Different mass concentrations of TNF-α(5, 10, 20, 40 ng/ml) were used to establish the pyroptosis model with TNF-α(0 ng/ml) as the control group. Cell viability was detected by CCK-8 method and proteins of pyroptosis signal were detected by Western blot. The levels of IL-1β and IL-18 in cultured supernatants were examined by ELISA kits. The expression of gasdermin D(GSDMD) in chondrocytes was detected by immunofluorescence. Scanning electron microscope was used to observe the morphological changes of chondrocyte. Results: Compared with the control group, the cell viability of rat chondrocytes gradually decreased with the increase of TNF-α concentration and the expression of nucleotide-binding and oligomerization domain-like receptor containing protein 3(NLRP3), caspase-1, GSDMD and Phospho-NF-κB p65(P-p65) proteins increased. Furthermore, TNF-α(20 ng/ml) could up-regulate the expression of matrix metalloproteinase-13(MMP-13), the fluorescence expression of GSDMD and the levels of IL-1β and IL-18 while the expression of Col Ⅱ was distinctly reduced. What′s more, the articular chondrocytes were swollen,and the microstructure was destroyed. Conclusion TNF-α(20 ng/ml) can cause the swelling and death of rat chondrocytes, degradation of cartilage matrix and activation of pyroptosis signaling pathway. The pyroptosis model of rat chondrocytes was successfully established.