Objective:To further investigate the safety and efficacy of Belimumab in the treatment of patients with systemic lupus erythematosus (SLE).Methods:All SLE patients treated with Belimumab from May 1, 2020 to February 1, 2022 in Peking Union Medical College Hospital were retrospectively collected and analyzed. The clinical manifestations, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) score, and laboratory test such as levels of anti-dsDNA antibody, the medication before and after Belimumab treatment, adverse events were collected. Normally distributed data were tested using the t-test, otherwise the Wilcoxon paired signed rank test was used. Results:A total of 81 patients were enrolled in this study. The use of belimumab could significantly decrease the SLEDAI-2000 score [10.00(7.75, 12.00) vs. 4.00(3.75, 6.00), Z=-5.38, P<0.001], ESR of SLE patients [19.50(12.75, 32.25) mm/1 h vs. 14.00(7.75, 20.25) mm/1 h, Z=-3.71, P=0.003], anti-dsDNA titer detected by CLIFT [300.00 (117.00, 864.00) vs. 183.00(100.00, 471.00), Z=-4.15, P=0.001], meanwhile, increase the complement C3 [0.78 (0.62, 0.97)g/L vs. 0.69 (0.55, 0.84)g/L, Z=-4.68, P<0.001], and the complement C4 [0.12 (0.08, 0.19)g/L vs. 0.10 (0.05, 0.14)g/L, Z=-4.78, P<0.001]. We also observed that with the use of Belimumab, the dosage of Glucocorticoids decreased significantly, which were [10.00(7.50, 22.50) mg vs. 7.50(5.00, 10.00) mg, Z=-4.90, P<0.001]. In addition, the antibody of IgG, IgA and IgM decreased significantly. Only one patient stopped the administration of Belimumab due to the low level of immunoglobulin. Conclusion:Belimumab can alleviate disease activity of patients with SLE and help in safely tapering the daily dose of glucocorticoid with good safety.

ObjectiveTo determine the resistance of adult Culex quinquefasciatus and Musca domestica to commonly used insecticides in Dazhu District of Chongqing in 2023， and provide scientific evidence for rational use of hygienic insecticides. MethodsDrug resistance was determined by using adult mosquito contact tube method and adult fly drop method. ResultsIn 2023， the 24-hour mortality rate of adult Culex quinquefasciatus in Dazu District， Chongqing， against permethrin （0.25%）， beta-cypermethrin （0.025%）， deltamethrin （0.025%）， malathion （5%） and propoxur （0.1%） was 37.35%， 21.92%， 28.33%， 96.43%， and 95.38%， respectively. The median lethal dose （LD₅₀） value of female adult Musca domestica against beta-cypermethrin （95.8%）， chlorpyrifos （97%）， deltamethrin （90%） and dichlorvos （95%） was 2.572 μg， 0.329 μg， 0.406 μg， and 0.492 μg， respectively， with resistance of 829.68， 7.65， 53.42， and 46.42 folds to the above tested insecticides． ConclusionAdult Culex quinquefasciatus and Musca domestica in Dazu District show various degrees of resistance to commonly used insecticides. It warrants suspending the insecticides with high resistance， whereas mixedly and alternatively administering the insecticides with possible resistance and low resistance. Additionally， we should continue to monitor the resistance and guide the rational use of insecticides.

Objective To investigate the influencing factors of Mismatch ratio in computed tomography perfusion(CTP)and dif-fusion weighted imaging(DWI)to assess the lesion outcome after treatment in patients with acute ischemic stroke(AIS).Methods Whether there were any differences in clinical and imaging data of AIS patients were analyzed retrospectively between the Mismatch ratio＞1.2 group and the Mismatch ratio≤1.2 group,and between the hemorrhagic transformation group and the non-hemorrhagic transformation group.Results The age of onset and National Institutes of Health Stroke Scale(NIHSS)score of AIS patients in the group with Mismatch ratio＞1.2 were greater than those in the group with Mismatch ratio≤1.2.The Mismatch ratio＞1.2 group had lower incidence of hyperlipidemia,new infarct foci,and higher hypercoagulability,cerebral hemorrhage,as well as large cerebral infarction.The NIHSS score was higher in the hemorrhagic transformation group than the non-hemorrhagic transformation group,and the incidence of large cerebral infarction and digital subtraction angiography(DSA)thrombectomy was higher in the former than in the latter.Multifactorial logistic analysis showed that age,NIHSS score,and hyperlipidemia were independent risk factors for AIS patients with Mismatch ratio＞1.2 and large cerebral infarction was an independent risk factor for hemorrhagic transformation.Conclusion The Mismatch ratio in CTP is correlated with age,NIHSS score,and hyperlipidemia in patients with AIS and large cerebral infarction is correlated with hemorrhagic transformation.

Inhibitory cells derived from bone marrow are a kind of inhibitory cells derived from bone marrow.These cells are not only related to tumor growth,but also participate in the inflammatory immune process.Therefore,we established a rat model of chronic osteomyelitis,and used gemcitabine to inhibit the cell growth ratio of MDSCs.We detected the ratio of MDSCs in bone marrow and spleen of rats by flow cytometry and immunofluorescence,detected the changes of inflammatory factors in peripheral blood by ELISA,and analyzed the inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-11)in peripheral blood of normal rats,osteomyelitis rats and rats after gemcitabine inhibition.The results showed that the proportion of MDSCs cells in bone marrow and spleen of osteomyelitis model rats was increased,but it was significantly decreased in gemcitabine group(P<0.05).Levels of inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-17,IFN-γ,TGF-β)were positively correlated with the change of MDSCs cell proportion(P<0.05).From the results,it can be inferred that the change of the proportion of MDSCs cells in rat osteomyelitis is positively related to the inflammatory factors,and gemcitabine can reduce inflammatory factors by inhibiting MDSCs.

BACKGROUND: Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL. METHODS: The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens. RESULTS: We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo . CONCLUSION Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.
Humans ; Animals ; Mice ; Rituximab/therapeutic use* ; Hippo Signaling Pathway ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Prognosis ; Semaphorins/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics*

Objective:To analyze the clinical characteristics of elderly-onset gouty arthritis and risk factors of tophi.Methods:A total of 1 239 gout patients were retrospective selected in the outpatient department of the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University from 2016 to 2022. According to age of onset, they were divided into the young and middle-aged group(aged<60) consisted of 826 cases, and the elderly group(aged≥60) consisted of 413 cases. Compare the clinical characteristics of elderly with Young and Middle-aged patients.Results:The systolic blood pressure, fasting blood glucose, creatinine, regular exercise, comorbidities, and tophi in the elderly group was higher than that in the middle-aged and young group. The proportion of diastolic blood pressure, serum triglycerides, eGFR, serum uric acid, alcohol consumption rate, and family history of gout was lower than that of young and middle-aged group( P<0.05); In the elderly-onset group, the initial site of arthritis was commonly observed in the first metatarsophalangeal joint. The proportion of the first attack with the upper limb joint was higher in old age group than in young and middle age group( P<0.05). Renal underexcretion type was the main subtype in the elderly group, and the proportion of overproduction type was higher than that of the young and middle-aged group( P<0.05). The logistic regression analysis showed that age, urea nitrogen, disease duration≥10 years and family history of gout were risk factors for tophi in elderly patients( P<0.05). Conclusion:The elderly-onset gout has unique clinical characteristics, characterized by a higher prevalence of tophi, a higher rate of complications. An initial site of arthritis commonly observed in the first metatarsophalangeal joint and the predominant type of uric acid excretion is renal excretion impairment. Early diagnosis and treatment, control of blood uric acid levels, smoking cessation and alcohol, regular exercise should be applied to prevent or delay the formation of tophi.

Objective　To provide a data foundation not only for food safety supervision and pollution source tracing, but also for the clinical treatment of drug-resistant bacteria in barreled drinking water, the drug resistance and type Ⅲ secretion system (T3SS) virulence genes carriage of Pseudomonas aeruginosa detected in barreled drinking water in Hainan Province were investigated, and the correlative relationship between strain ribosomal subtypes and virulence genes were then discussed. Methods The drug resistance of the isolated 55 strains of Pseudomonas aeruginosa was confirmed by using VITEK 2 Compact automatic microbial drug sensitivity system, and the T3SS virulence genes ExoU, ExoS, ExoT and ExoY were amplified by PCR, bacterial strain subtypes and homology were analyzed by the RiboPrinter automatic microbial gene fingerprint identification system. Results The drug sensitivity results showed that Pseudomonas aeruginosa isolated from barreled water had relatively low drug resistance, though one strain of multidrug-resistant Pseudomonas aeruginosa was discovered, resistant to imipenem, ciprofloxacin and cefepime. The distribution of T3SS virulence genes showed four genotypic combinations: ExoT+/ExoY+/ExoS+/ExoU- (45.45%, 25/55), ExoT+/ExoY+/ExoS-/ExoU+ (34.55%, 19/55), ExoT+/ExoY-/ExoS-/ExoU+(18.18%, 10/55), ExoT+/ExoY+/ExoS+/ExoU+ (1.82%, 1/55). Ribosomal typing results showed that the Pseudomonas aeruginosa strains were divided into six subtypes, the numbers of each subtype accounted for 24 (43.64%), 1 (1.82%), 25 (45.45%), 1 (1.82%), 3 (5.45%) and 1 (1.82%) respectively, with subtype Ⅰ and subtype Ⅲ being dominant. The main T3SS genotypes of the top two subtype I and subtype III were ExoT+/ExoY+/ExoS-/ExoU+ (16/24, 66.67%) and ExoT+/ExoY+/ExoS+/ExoU- (22/25, 88%). Conclusions The T3SS secretion system exhibits the characteristics of multiple virulence genes' coordinated expression, and there is a certain correlation between subtypes of bacterial strains and virulence genotypesThe exploration of the relationship between them provides guidance for tracing the source of Pseudomonas aeruginosa contamination, production control, clinical treatment in barrelled drinking water, and preliminarily establishes the initial data of local Pseudomonas aeruginosa strains in barrelled drinking water as well the related drug sensitivity data in Hainan.

Objective:To investigate the effect of digoxin on bleomycin-induced pulmonary fibrosis in mice, and investigate its possible mechanism through in vitro and in vivo experiments. Methods:① In vivo experiment: 60 C57/BL6J mice were randomly divided into control group, pulmonary fibrosis model group (model group), pirfenidone (300 mg/kg) group, digoxin 1.0 mg/kg and 0.2 mg/kg groups, with 12 mice in each group. The pulmonary fibrosis model of mice was reproduced by single intratracheal infusion of bleomycin (5 mg/kg). The control group was given the same amount of sterile normal saline. From the next day after modeling, each group was received corresponding drugs by intragastric administration once a day for 28 days. Control group and model group were given the same amount of normal saline. The mice were sacrificed and the lung tissue was collected to detect the lung coefficient. After hematoxylin-eosin (HE) and Masson staining, the lung tissue morphology and collagen changes were observed under light microscope. Immunohistochemistry was used to detect the positive expressions of α-smooth muscle actin (α-SMA) and extracellular matrix (ECM) collagen (COL-Ⅰ and COL-Ⅲ) in lung tissue. The protein expressions of ECM fibronectin (FN), transforming growth factor-β (TGF-β) and phosphorylation of Smad3 (p-Smad3) in lung tissue were detected by Western blotting. ② In vitro experiment: human embryonic lung fibroblast-1 (HFL-1) cells were cultured and divided into blank control group, fibroblast activation model group (model group), pirfenidone (2.5 mmol/L) group and digoxin 100 nmol/L and 50 nmol/L groups when cell density reached 70%-90%. After 3-hour treatment with corresponding drugs, except blank control group, the other groups were treated with TGF-β for 48 hours to establish fibroblast activation model. The expressions of α-SMA, FN and p-Smad3 proteins and the phosphorylations of phosphatidylinositol-3-kinase (PI3K)/Akt pathway proteins PI3K and Akt (p-PI3K, p-Akt) were detected by Western blotting. Results:① In vivo, compared with the control group, the alveolar structure of mice in the model group was significantly damaged, a large number of inflammatory cells infiltrated, collagen deposition in the lung interstitium was increased, the deposition of ECM in the lung tissue was also increased, and the expressions of α-SMA, FN, TGF-β and p-Smad3 protein were increased, indicating that the model of bleomycin-induced pulmonary fibrosis in mice was successfully prepared. Compared with the model group, digoxin significantly inhibited airway inflammation and collagen fiber deposition, reduced ECM deposition, and decreased the protein expressions of α-SMA, FN, TGF-β and p-Smad3, while the effect was better than that of the pirfenidone group, and the digoxin 1.0 mg/kg group had a better effect except FN [α-SMA ( A value): 5.37±1.10 vs. 9.51±1.66, TGF-β protein (TGF-β/GAPDH): 0.09±0.04 vs. 0.33±0.23, p-Smad3 protein (p-Smad3/GAPDH): 0.05±0.01 vs. 0.20±0.07, all P < 0.01]. ② In vitro, compared with the blank control group, the expressions of FN, α-SMA, p-Smad3 and PI3K/Akt signaling proteins in the model group were increased, indicating that the fibroblast activation model induced by TGF-β was successfully reproduced. Compared with the model group, digoxin significantly inhibited fibroblast activation, and decreased the expressions of FN, α-SMA, p-Smad3, and PI3K/Akt pathway proteins, moreover, the effect was better than that of the pirfenidone group, and decreased FN, SMA and p-Akt protein expressions were more obvious in digoxin 100 nmol/L group [FN protein (FN/GAPDH): 0.21±0.15 vs. 0.88±0.22, α-SMA protein (α-SMA/GAPDH): 0.20±0.01 vs. 0.50±0.08, p-Akt protein (p-Akt/GAPDH): 0.30±0.01 vs. 0.65±0.10, all P < 0.01]. Conclusion:Digoxin could suppress the pulmonary fibrosis in mice induced by bleomycin, which might be associated with the regulation of fibroblast activation via suppressing PI3K/Akt signaling pathway in a dose-dependent manner.

Objective:To investigate the risk factors of in-hospital mortality in elderly patients with traumatic brain injury (TBI).Methods:A case control study was conducted on 709 elderly patients with TBI admitted to Luhe Hospital, Capital Medical University from January 2012 to October 2018, including 468 males and 241 females; aged 60-97 years [(70.4±8.5)years]. Patients were divided into death group ( n=82) and survival group ( n=627) based on death or not during hospitalization. Data of the two groups were documented, including gender, age, causes of injury (traffic accident injury, fall injury, assault injury or others), history of comorbidities (hypertension, coronary heart disease, diabetes or coronary heart disease), Glasgow coma score (GCS) on admission, operation modalities (trepanation and drainage, hematoma evacuation, decompressive craniectomy or intracranial pressure monitoring), complications (pneumonia, stress ulcer, electrolyte imbalance, hypoproteinemia or secondary epilepsy) and length of hospitalization. Univariate analysis was used to analyze the correlation between the above factors and in-hospital mortality in elderly patients with TBI. Multivariate Logistic regression analysis was used to determine the independent risk factors for their in-hospital mortality. Results:Univariate analysis showed that sex, causes of injury, hypertension, cerebral infarction, diabetes, GCS on admission, hematoma evacuation, decompressive craniectomy, intracranial pressure monitoring, pneumonia, stress ulcer and length of hospital stay were correlated with in-hospital mortality in elderly patients with TBI ( P<0.05 or 0.01), while there was no correlation with age, history of coronary heart disease, trepanation and drainage, electrolyte imbalance, hypoproteinemia and secondary epilepsy (all P>0.05). Multivariate Logistic regression analysis showed that fall injury ( OR=0.28, 95% CI 0.08-0.96, P<0.05), hypertension ( OR=0.29, 95% CI 0.10-0.84, P<0.05),GCS of 9-12 points on admission ( OR=12.98, 95% CI 4.70-35.84, P<0.01), GCS of 3-8 points on admission ( OR=33.67, 95% CI 14.01-80.93, P<0.01) and length of hospital stay<11 days ( OR=0.06, 95% CI 0.02-0.13, P<0.01) were significantly associated with their in-hospital mortality. Conclusions:Fall injury, hypertension, GCS≤12 points on admission and length of hospital stay <11 days are independent risk factors for in-hospital mortality in elderly patients with TBI, especially that patients with GCS of 3-8 points on admission have higher in-hospital modality than patients with GCS≥ 9 points, indicating the importance of above independent risk factors in evaluating outcome.

By searching for the Canadian Licensed Natural Health Products Database, (LNHPD), this paper analyzed the characteristics and current status of 92 Chinese patent medicines successfully registered and listed in Canada, and found that the enterprises of successfully registered enterprises are mainly located in areas with better development condition of Traditional Chinese Medicine (TCM) such as Beijing, Guangdong and Tianjin; The successfully registered Chinese patent medicines include 64 kinds of single medicine or medicine with single active ingredient (69.6%) and 28 kinds of compound medicine (30.4%), the forms of the dosage are mainly tablets and capsules, which have the characteristics of accuracy in dosage and stable physicochemical properties. There are also granules, solutions, powders and other dosage forms, which can be preserved for a long time and have low requirements on technic and environment. These Chinese patent medicines are mainly used to treat respiratory and circulatory system diseases, some are used to treat urogenital and digestive system diseases, and few are used to treat difficuilt diseases like tumors, diabetes. There are some other health care products. It is suggested to strengthen the connection between domestic standards of TCM registration and international standards, and promote the scientific and technological capacity of relevant enterprises, and encourage enterprises to strengthen international registration of advantageous products, so as to accelerate the speed of international development of TCM in China.