Objective To investigate the expression level and clinical application value of serum resistin in patients with systemic lu-pus erythematosus(SLE).Methods Forty-five SLE patients visited Nanjing Drum Tower Hospital,Clinical College of Nanjing Uni-versity of Chinese Medicine from January to August 2023 were enrolled in the study.The patients were scored and grouped according to the SLE disease activity index(SLEDAI),with SLEDAI＜9 score in the inactive group(n=32)and SLEDAI≥9 score in the active group(n=13).Thirty-four healthy individuals who underwent physical examination in our hospital were recruited as healthy controls.The clinical data and laboratory related indicators such as urine protein and serum complement C3 levels were collected from SLE pa-tients and healthy controls.Serum resistin levels were detected by enzyme-linked immunosorbent assay(ELISA).The clinical screening value of serum resistin for SLE was evaluated with the receiver operating characteristic(ROC)curve.The correlations of serum resistin levels with different laboratory indicators were determined by Pearson correlation analysis.Results The serum resistin levels in SLE patients([7.64±0.64]ng/mL)were significantly higher than that in healthy controls([2.56±0.43]ng/mL),and the difference was statistically significant(t=6.195,P＜0.01).The serum resistin levels in active SLE patients([10.10±1.45]ng/mL)were significant-ly higher than that in inactive SLE patients([6.64±0.60]ng/mL),and the difference was statistically significant(t=2.632,P＜0.05).The area under the ROC curve(AUCROC)of serum resistin for screening SLE was 0.897.When the cut-off value was 5.893 ng/mL,the sensitivity was 86.67%and the specificity was 82.35%.The serum resistin level in SLE patients was positively correlated with urine protein(r=0.692,P＜0.01),while negatively correlated with serum complement C3(r=-0.354,P＜0.05).Conclusion The expression levels of serum resistin in SLE patients are significantly increased and positively correlated with SLE disease activity and urine protein.Serum resistin may become a novel biomarker for the diagnosis and therapeutic effect assessment of SLE.

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.

Objective:To explore the effects of phloroglucinol on transfer outcome of in vitro fertilization-embryo transfer (IVF-ET). Methods:Retrospective analysis of 4289 cases of infertility patients treated with IVF-ET in the Department of Reproductive Medicine, the Second Affiliated Hospital of Zhengzhou University from January 1, 2015 to November 30, 2018 was performed. According to the pregnancy outcome, all patients were divided into pregnancy group and non-pregnancy group to analyze the risk factors affecting the pregnancy outcome. According to medication before transfer, all patients were divided into no medication group (group A), preoperative intravenous infusion of atosiban group (group B), preoperative and intraoperative injection of atosiban group (group C) and interoperative intravenous infusion of phloroglucinol group (group D). The pregnancy outcomes, occurrence of adverse reactions during and after treatment were compared among the four groups.Results:Age, number of high-quality embryos, and medication methods before transfer were independent factors influencing pregnancy outcomes in patients undergoing IVF-ET ( P=0.031, P=0.039, P=0.020). The embryo implantation rate, the biochemical pregnancy rate and the clinical pregnancy rate of group D were significantly higher than those in group A (all P<0.001), group B (all P<0.001) and group C ( P<0.001， P<0.001， P=0.001), while the ectopic pregnancy rate was significantly lower than that in group A, group B and group C (all P<0.001). The abortion rate in group D was lower than that in group A ( P<0.001). During treatment period and after treatment, there were no discomfort complains and allergic reactions in the four groups. There were no birth defects in all born babies. Conclusion:The medication method is an independent factor influencing pregnancy outcomes of patients undergoing IVF-ET. Intraoperative intravenous infusion of phloroglucinol can significantly increase embryo implantation rate and pregnancy rate of IVF-ET patients, and reduce their abortion rate.

Objective:To explore the effects of phloroglucinol on transfer outcome of in vitro fertilization-embryo transfer (IVF-ET). Methods:Retrospective analysis of 4289 cases of infertility patients treated with IVF-ET in the Department of Reproductive Medicine, the Second Affiliated Hospital of Zhengzhou University from January 1, 2015 to November 30, 2018 was performed. According to the pregnancy outcome, all patients were divided into pregnancy group and non-pregnancy group to analyze the risk factors affecting the pregnancy outcome. According to medication before transfer, all patients were divided into no medication group (group A), preoperative intravenous infusion of atosiban group (group B), preoperative and intraoperative injection of atosiban group (group C) and interoperative intravenous infusion of phloroglucinol group (group D). The pregnancy outcomes, occurrence of adverse reactions during and after treatment were compared among the four groups.Results:Age, number of high-quality embryos, and medication methods before transfer were independent factors influencing pregnancy outcomes in patients undergoing IVF-ET ( P=0.031, P=0.039, P=0.020). The embryo implantation rate, the biochemical pregnancy rate and the clinical pregnancy rate of group D were significantly higher than those in group A (all P<0.001), group B (all P<0.001) and group C ( P<0.001， P<0.001， P=0.001), while the ectopic pregnancy rate was significantly lower than that in group A, group B and group C (all P<0.001). The abortion rate in group D was lower than that in group A ( P<0.001). During treatment period and after treatment, there were no discomfort complains and allergic reactions in the four groups. There were no birth defects in all born babies. Conclusion:The medication method is an independent factor influencing pregnancy outcomes of patients undergoing IVF-ET. Intraoperative intravenous infusion of phloroglucinol can significantly increase embryo implantation rate and pregnancy rate of IVF-ET patients, and reduce their abortion rate.

Objective To investigate the effhect of ultrasound-guided nerve block on the prognosis of patients undergoing laparoscopic cholecystectomy.Methods A total of 150 cases undergoing elective laparoscopic cholecystectomy in our hospital was used as the research object,and randomly divided into control (n =75) and observation (n =75) groups.The control group used punctured local infiltration analgesia,and observation group used the transversus abdominis plane block (TAP) combined with local infiltration analgesia hole.The postoperative awake time,hemodynamic changes,pain score,and analgesic use were compared between two groups.Results The recovery time was significantly reduced in the observation group (9.7 ± 2) minutes compared to the control group (23.9 ± 2.4) minutes.The additional total dose of analgesics and average additional times were significantly lower in the observation group compared to the control group (P ＜0.05).The pain score were 0.99 ±0.22 after waking,1.05 ±0.14 at the postoperative 6 h,1.13 ±0.23 at the postoperative 24 h,and 1.40 ±0.38 at the postoperative 48 h in the observation group,which was significantly lower than the corresponding 3.99 ± 0.36,3.67 ± 0.43,3.39 ± 0.38,and 3.93 ± 0.20 in the control group (P ＜ 0.05).With the postoperative time,postoperative 48 h in two groups of visual pain scores were significantly higher than that of 24 h after the operation (P ＜ 0.05).The incidence of adverse reactions was no significant difference between observation group (36％) and control group (32％) (P ＞ 0.05).Conclusions Ultrasound-guided nerve block can obviously reduce postoperative pain,reduce drug use frequency and dosage,significantly improve postoperative outcomes,and does not increase the incidence of adverse drug reactions.It is worthy of clinical reference.

Objective To investigate the abnormality of intrahepatic biliary epithelial cells autophagy in primary biliary cirrhosis (PBC) mice,and explore the mechanism of UC-Mesenchymal stem cell (MSCs) in treating PBC.Methods After establishing the PBC model,we divided them into the PBC model group;the UC-MSCs treatment group and the Stattic group [Signal transducer and activator of transcription 3 (STAT3) inhibitor group].Six mice were used as the control group.Liver pathology and the serum pyruvate dehydrogenase complex E2 subunit (PDC-E2) antibody titers were detected.Autophagosome of the intrahepatic biliary epithelial cell was observed by electronic microscope.Protein levels of STAT3/pSTAT3,Beclin-1 were detected by western blot.We cultured human intrahepatic biliary epithelial cells in vitro,and down regulated STAT3.After stimulated by GCDC,we co-cultured them with UC-MSCs,and collected the cells in order to detect LC3 Ⅱ.The measurement data were compared with t test or single factor analysis of variance.Results Compared with the control group,periportal inflammatory cell infiltration and granuloma formation were observed in the PBC group.MSCs treatment decreased the infiltration of inflammatory cells.The level of antiPDC-E2 of the PBC group (107±18) ng/ml was higher than that of the control group (42±6) ng/ml (q=6.326,P＜0.01),MSCs treatment down regulated anti-PDC-E2 level (43±4) ng/ml (q=5.801,P＜0.01).More autophagosomes in the PBC group (5.00±1.29) than the control group (1.75±0.25) were observed (q=4.061,P＞0.05).Western blot showed that the level of Beclin-1 was higher in PBC group (1.80±0.36) than the control group (0.40±0.20) (q =6.757,P＜0.01),MSCs reduced the expression of Beclin-1 (0.86±0.06)(q=4.536,P＜0.05) as well as Stattic (0.72±0.03) (q=5.226,P＜0.05).PBC group had a higher expression level of STAT3 (1.80±0.42) (q=5.730,P＜0.05) and pSTAT3 (2.04±0.29)(q=6.492,P＜0.01) than the control group (0.50±0.05)(0.91±0.14).MSCs treatment decreased the expression of STAT3 (0.51±0.13)(q =5.703,P＜0.01) and pSTAT3 (0.76±0.07) (q =7.388,P＜0.01) in intrahepatic biliary epithelial cells.After down regulated STAT3 of HiBECs,MSCs reduced the expression of LC3 Ⅱ of HiBECs.Conclusion The intrahepatic biliary epithelial cells autophage of PBC mice is abnormal,MSCs can alleviate PBC by down regulating the autophage of intrahepatic biliary epithelial cells via STAT3.

Objective The purpose of this study is to observe the changes of immune cell subsets in lupus mice after umbilical cord mesenchymal stem cells (UC-MSCs) transplantation. Methods B6.MRL-Faslpr lupus mice were randomly divided into the following three groups: the UC-MSCs treated group, the fibroblast like synoviocytes (FLS) treated group and the untreated group. MSC (1×106) or FLS (1×106) were injected into the tail vein of lupus mice respectively. Four weeks after treatment, the spleen index was calculated. The pathological changes of kidney were assessed by HE staining. The frequencies of immune cell subsets in spleen and macrophage in kidney as well as abdominal cavity were analyzed by flow cytometry. Data were analyzed with t test. Results The spleen index of UC-MSCs treated lupus mice [(79 ±9) mg/10 g] and IgG level [(7.5±1.5) mg/ml] were significantly decreased when compared with FLS treated group [(147±23) mg/10 g, t=2.78, P<0.01] [(17.0 ±2.8) mg/ml, t=3.00, P<0.01] and the untreated group [(156 ±16) mg/10 g, t=4.29, P<0.01] [(16.7 ±1.6) mg/ml,t=4.01, P<0.01]. HE staining also showed that the pathological changes of kidney were alleviated after MSCs transplantation. In addition, the frequency of plasma cells in the untreated group [(2.61 2± 0.318)% vs (0.306±0.017)%, t=7.22, P<0.01] and the FLS treated group [(2.412±0.297)% vs (0.306±0.017)%, t=7.07, P<0.01] were markedly higher than MSCs treatment [(0.306 ±0.017)%]. Moreover, the frequency of CD25+Foxp3+/CD4+Treg in the MSCs treated group [(15.08±0.81)%] was significantly increased compared with the untreated group [(8.02 ±0.47)%, t=7.45, P<0.01] and FLS treated group [(8.80 ±0.23)%, t=7.39, P<0.01]. MSCs treatment resulted in a decrease in CXCR5+PD1+/CD4+Tfh and IFNγ+/CD4+Th1 subset, compared with the untreated group [(14.3±1.5)%vs (31.5±3.3)%, t=5.25, P<0.01] [(1.78±0.27)% vs (5.93±1.56)%, t=2.60, P<0.05] and the FLS treated group [(14.3±1.5)%vs (28.8±2.2)%, t=5.49, P<0.01] [(1.78±0.27)%vs (4.88±0.81)%, t=3.61, P<0.01]. The frequency of macrophage in kidney of the MSCs treated group [(3.52 ±0.37)%] was markedly increased compared with the untreated group[(1.58±0.29)%, t=3.25, P<0.01], while neither the IL4+/CD4+Th2 subset nor the IL17+/CD4+Th17subset and the frequency of macrophage in abdominal cavity showed significant changes in the three groups. Conclusion These findings suggest that the therapeutic effects of MSCs on lupus mice may mediate through increasing the frequency of spleen Treg and renal macrophage and decreasing the frequency of Tfh, Th1 and plasma cells.

OBJECTIVETo explore the molecular mechanism underlying the DEL phenotype among RhD negative ethnic Han individuals from Jiangsu, China.

METHODSThe DEL phenotype was determined by an adsorption elution test among 57 RhD negative blood donors. The Rh C, c, E, and e phenotypes were detected by a tube method. PCR with sequence-specific primering (PCR-SSP) assay was used to determine the RHCE genotypes. The RHD gene of the DEL individuals were amplified with polymerase chain reaction and subjected to Sanger sequencing analysis.

RESULTSAmong the 57 RhD negative donors, 10 (17.54%) were determined as having the DEL phenotype. The major RhCE phenotypes for DEL and RhD negative cases were RhCcee (80.0%) and Rhccee (61.7%), respectively. All RHD gene sequences of the 10 individuals have harbored a G>A mutation at position 1227 of exon 9.

CONCLUSIONA proportion of RhD negative individuals determined by routine serological method are actually DEL with RHD gene mutations. RHD *1227A is the most prevalent DEL genotype among ethnic Han Chinese from Jiangsu. Further research on the phenotype and underlying molecular mechanism of DEL is important for blood transfusion.

Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Blood Donors ; China ; ethnology ; Exons ; Genotype ; Humans ; Male ; Molecular Sequence Data ; Phenotype ; Polymorphism, Genetic ; Rh-Hr Blood-Group System ; genetics

Objective To study the blood concentration of hydroxychloroquine in patients with systemic lupus erythematosus (SLE) treated with different doses, and analyze the relationship between blood concentration of hydroxychloroquine and disease activity, and evaluate its safety.Methods Forty SLE patients were randomly divided into 2 groups, each group contained 20 cases.The patients in group A were treated with hydroxychloroquine (0.4 g, qd), while patients in group B were treated with hydroxychloroquine (0.2 g, qd).The treatment lasted more than six months in every patient.The blood concentrations of hydroxychloro-quine were detected by high performance liquid chromatography.The clinical and laboratory indices were collected.The systemic lupus erythematosus disease activity index (SLEDAI) score was recorded.The doses and varieties of combined hormone, immunosuppressant were recorded.The correlation of blood concentration of hydroxychloroquine and disease activity was analyzed.The significance was determined by Student's t test and Pearson correlation analysis.Results In SLE patients, the average blood concentration of hydro-xychloroquine was (402±190) ng/ml in group A and (150±60) ng/ml in group B (t=7.471, P＜0.01).The disease activities of patients in the two groups showed no significant difference (t=-0.172, P＞0.05).The platelet counts of patients in group A were significantly higher than those in group B[(188±88)×109/L vs (158 ±87) ×109/L] (t=4.375, P＜0.05).However, the other laboratory parameters showed no significant difference between the two groups (P＞0.05).Conclusion The results of this study indicate that the blood concentrations of hydroxy-chloroquine are significantly different in different dosages.The high dose of hydroxy-chloroquine is related to high platelet number in lupus patients.These findings suggest that hydroxychloroquine is safe and effective for SLE patients.

Objective To investigate the effect of phosphoinositide-3-kinase inhibitor LY294002 on the differentiation of human embryonic stem cells (HESC) into more mature insulin-producing cells. Methods HESCs were induced to differentiate into insulin-producing cells through five stages. Nicotinamide and B27 (group B27), nicotinamide and LY294002 (group LY) were used to induce the nesting positive cells into mature insulin-producing cells. The morphological change of each stage was observed under microscope , and expressions of insulin, c-peptide, somatostatin and glucagon were identified by immunofluorescence staining. Results After 14 days in stage 5 , there was no significant difference in rate of insulin positive cells between group LY and group B27 (P﹥0.05), but rates of somatostatin and glucagon positive cells in group LY were lower than those in group B27(P﹤0.05). Furthermore, the co-stained rate of somatostatin and insulin in group LY was also lower than that in group B27 (P﹤0.05). Conclusion HESCs can be induced to differentiate into more mature insulin-producing cells by phosphoinositide-3-kinase inhibitor LY294002 in serum-free culture medium.