Objective To study anti-inflammatory activities of oridonin derivatives without Michael fragment. Methods Two oridonin sulfonylureas were designed and synthesized by a photocatalysis reaction and a scaffold hopping strategy. The inhibitory rate of IL-1β was selected for anti-inflammatory activity evaluation. Results Both compound ZM658 and ZM659 revealed potent anti-inflammatory activities with the values of 69.3% and 59.7% in THP-1 cells, respectively. Moreover, two compounds also showed dose-dependent and low cytotoxicity. Conclusion The result indicated that Michael receptor fragment of oridonin could be substituted with sulfonylurea group.

【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.

OBJECTIVE To investigate the effect of myricetin(Myr) on immune function in rats with inflammatory bowel disease(IBD) by regulating the cAMP/PKA/CREB signaling pathway. METHODS IBD rat models were established and separated into control group, model group, low, medium, and high dose Myr(Myr-L, Myr-M, Myr-H, 28, 56, 112 mg·kg−1·d−1 Myr) groups, and high dose Myr+PKA inhibitor H89(Myr-H+H89 112 mg·kg−1·d−1 Myr+7 mg·kg−1·d−1 H89) group. The disease activity index(DAI) of rats was scored; immune function indicators and colon length were measured; the levels of IL-6, IL-17A, TNF-α, and cAMP in serum were determined by the kit; the pathological changes of colon tissue were observed by HE staining; the proportion of Treg cells was determined by flow cytometry; immunohistochemistry was used to detect the expression of MPO in colon tissue; Western blotting was used to determine cAMP/PKA/CREB signaling pathway related proteins. RESULTS Compared with the control group, the colon tissue cells in the model group were disorderly arranged, with a large number of inflammatory cell infiltration, severe ulceration, a large number of cell necrosis, mucosal edema, the DAI score, IL-6, TNF-α, and IL-17A levels, spleen coefficient, thymus coefficient, and MPO optical density values were obviously increased(P<0.05), the colon length, Treg cell ratio, cAMP concentration, p-PKA/PKA, and p-CREB/CREB levels were obviously reduced(P<0.05). Compared with the model group, the arrangement of colon tissue cells in the Myr-L, Myr-M, and Myr-H groups was relatively neat; mucosal edema inflammatory cell infiltration, cell necrosis and ulcer phenomenon were reduced; the DAI score, IL-6, TNF-α, and IL-17A levels, spleen coefficient, thymus coefficient, and MPO optical density values were gradually reduced(P<0.05); the colon length, Treg cell ratio, cAMP concentration, p-PKA/PKA, and p-CREB/CREB levels were gradually increased(P<0.05). Compared with the Myr-H group, the pathological changes in the colon tissue of the Myr-H+H89 group worsened, the DAI score, IL-6, TNF-α, and IL-17A levels, spleen coefficient, thymus coefficient, and MPO optical density values were obviously increased(P<0.05), the colon length, Treg cell ratio, cAMP concentration, p-PKA/PKA, and p-CREB/CREB levels were obviously reduced(P<0.05). CONCLUSION Myr may inhibit inflammation levels, regulate immune function, and exert protective effects on IBD rats by activating the cAMP/PKA/CREB signaling pathway.

Objective To investigate the effects of β-sitosterol on the proliferation and apoptosis of colon cancer cell HCT116,and its regulation of on phosphoinositide 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Methods Cultivated colon cancer cells HCT116 in vitro and divided them into β-sitosterol High(240μmol/L)、medium(120μmol/L)and low-dose(60μmol/L)groups,set control group(0μmol/L).Applied different concentrations of β-sitosterol treatment of HCT116 cells.And 24h later,the cell proliferation and activity were determined by cell counting kit-8(CCK-8)method,the morphological changes observed under a microscope;Cell apoptosis was observed by Hoechst 33342 nuclear staining;Used cell colony formation assy to detect the colony forming ability of HCT116 cells;and Western blot was used to evaluate the expression of PI3K,p-Akt,Akt,Bcl-2 and Bax in cells.Used AutoDock software for molecular docking of β-sitosterol with Akt and PI3K.Results Compared with the control group,β-sitosterol could inhibit the proliferation of colon cancer HCT116 cells in a concentration dependent manner,inhibit their colony forming ability and promote cell apoptosis and inhibit the expression of p-Akt、PI3K、and Bcl-2 proteins in HCT116 cells and promotes the expression of Bax protein.The binding of β-sitosterol with PI3K and Akt proteins is relatively stable.Conclusion β-sitosterol may regulate the proliferation and apoptosis of HCT116 through inhibiting PI3K/Akt signaling pathway.

Objective:To construct 68Ga-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD44 as a novel atherosclerosis tracer targeting hyaluronic acid (HA), and evaluate its biological property and molecular imaging features. Methods:Low molecular weight (LMW) recombinant human CD44 protein was selected, and the C-terminal of the protein was modified by sulfonation and coupled to the bifunctional ligand NOTA to synthesize a novel molecular probe 68Ga-NOTA-CD44 targeting HA. The biological properties of the probe, such as labeling rate and in vitro stability, were studied. Three atherosclerotic plaque model mice and three normal C57BL/6 mice were studied by 68Ga-NOTA-CD44 microPET/CT imaging and pathological examination. Results:68Ga-NOTA-CD44 tracer was synthesized and purified with the radiochemical purity above 99%, and the specific activity was up to 62.22 MBq/nmol. lts stability was good in PBS, and the radiochemical purity was over 90% after incubation for 3 h. After intravenous injection, the probe was metabolized mainly by the kidneys, and its metabolic level decreased successively in the liver, lungs and blood. MicroPET/CT imaging results of atherosclerotic model mice suggested that the uptake in the plaque of abdominal aorta was higher at 60 min after injection, with SUV max and target/background ratio (TBR) max of 1.14±0.02 and 4.95±0.93, and the probe had certain atherosclerotic plaque eroded targeting, which was consistent with the pathological result. Conclusions:As a novel probe, 68Ga-NOTA-CD44 is simple to prepare and has a high labeling rate. It has good physicochemical properties and in vivo biological properties, and can display atherosclerotic eroded plaques sensitively. 68Ga-NOTA-CD44 has a promising prospect to be a new molecular probe for early noninvasive recognition of atherosclerotic eroded plaques.

Objective To evaluate the application effect of joint inventory management method in drug procurement and control management in multiple hospital areas.Methods Based on the joint inventory management model,four pilot drugs were selected from a certain group hospital by reasonable data processing methods for research.The effects of the model application were compared and analyzed from aspects such as inventory cost,turnover situation,and supply situation.Results After applying the joint inventory management model led by the central hospital,the inventory and amount of drugs in the three pilot hospitals were significantly reduced,with the inventory reduced by 31.93%and the average inventory amount decreased by 16.23%;The inventory turnover days had significantly decreased,with the turnover days of all three branches decreasing by more than one day;The drug shortage rate had significantly decreased,with the most significant change among the pilot drugs being the doxorubicin liposome injection,which had a 6.7%decrease in the shortage rate;The comparison results of each group of data showed statistical significance(P＜0.05).Conclusion Adopting a central hospital led joint inventory management model in multiple hospital areas could significantly improve the effectiveness of drug procurement management and inventory management,which enhanced the efficiency of hospital fund utilization.

Surgery is the mainstay of lung cancer treatment options.Traditionally,lobectomy has held its place as the gold standard for treating localized lung cancer,while sublobar resection,including wedge resection and segmentectomy,was primarily considered as an alternative,often reserved for patient ineligible to sustain a radical intervention.However,with the widespread application of computed tomography(CT)to clinical practice,the increasing detection rate of pulmonary ground glass nodules(GGNs)has reshaped this landscape.Ground glass opacity(GGO)in persistent lung nodules is an indicative factor of a favorable prognosis,typically corresponding to pathological changes such as atypical adenomatous hyperplasia(AAH),adenocarcinoma in situ(AIS),or adenocarcinomas predominantly featuring a lepidic growth pattern.A large number of retrospective studies have shown that sublobar resection can achieve satisfactory therapeutic outcomes for such lesions.A series of prospective studies from Japan have confirmed that for early-stage lung cancers dominated by GGOs,sublobar resection is also a viable curative surgical option.The follow-up data showed that there was no statistical difference in the survival status of these patients compared with that of pulmonary lobectomy.This article aims to delve into the role of limited lung resection in the context of lung adenocarcinoma presenting with GGO features.

Objective·To investigate the expression of miR-146a in peripheral blood CD4+T lymphocytes of patients with rheumatoid arthritis(RA)and its correlation with inflammatory cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Methods·A total of 30 active RA patients who received medical treatment and 30 healthy controls who underwent physical examinations at the People's Hospital of Longhua,Shenzhen from August 2019 to July 2021 were selected.Peripheral blood mononuclear cells(PBMCs)and CD4+T lymphocytes were isolated from venous blood extracted from RA patients and healthy controls,respectively.Quantitative real-time PCR(qPCR)was used to detect the expression of miR-146a in peripheral blood CD4+T lymphocytes,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of TNF-α and IL-6.After transfection of the peripheral blood CD4+T lymphocytes of RA patients with miR-146a mimic,the expression of miR-146a,TNF-α and IL-6 was detected again.The correlations between miR-146a expression and TNF-α and IL-6 expression in RA patients,both before and after transfection,were analyzed by using Pearson correlation coefficient.Results·Before transfection with miR-146a mimic,the expression levels of miR-146a,TNF-α and IL-6 in peripheral blood CD4+T lymphocytes of RA patients were significantly higher than those of healthy controls(all P＜0.001).After transfection,the expression of miR-146a in peripheral blood CD4+T lymphocytes of RA patients was significantly higher,and the expression of TNF-α and IL-6 was significantly lower(all P＜0.001).The results of Pearson correlation analysis showed that the expression of miR-146a in peripheral blood CD4+T lymphocytes of RA patients,both before and after transfection,was positively correlated with the expression of TNF-α and IL-6,respectively(r=0.959,P＜0.001;r=0.916,P＜0.001;r=0.971,P＜0.001;r=0.861,P＜0.001).Conclusion·miR-146a can regulate the levels of TNF-α and IL-6 in peripheral blood CD4+T lymphocytes of RA patients,indicating that miR-146a may play a role in the pathogenesis of RA.

AIM:The effects and mechanisms of paeoniflorin(PF)on sepsis-associated acute kidney injury(SA-AKI)in mice were investigated based on cellular pyroptosis and the JNK/NEK7/NLRP3 pathway.METHODS:A murine SA-AKI model was established by intraperitoneal injection of lipopolysaccharide(LPS).Twenty-four male C57BL/6J mice aged 6～8 weeks were divided into four groups(n=6)using a randomized numerical table method:control(Con)group(an equal amount of DMSO-containing PBS was injected intraperitoneally at the same time);LPS group(LPS was injected intraperitoneally at 15 mg/kg);LPS+PF group(PF was injected intraperitoneally at 50 mg/kg for 30 min prior to modeling);and LPS+PF+anisomycin group(intraperitoneal injection of PF 50 mg/kg and JNK agonist anisomycin 20 mg/kg 30 min before modeling).Samples were taken 24 h after modeling.HE staining was used to observe the pathological changes in renal tissues,and Paller scoring of renal injury was performed.ELISA was used to detect the levels of renal in-jury markers:blood creatinine(Scr),kidney injury molecule 1(KIM-1),and the inflammatory factors interleukin 1β(IL-1β)and IL-18.Western blot was used to detect changes in phosphorylated c-Jun N-terminal kinase(p-JNK),NIMA-relat-ed expressed kinase 7(NEK7),nucleotide oligomerization domain(NOD)-like receptor protein 3(NLRP3),and N-ter-minal fragment of gasdermin D(GSDMD-N)protein levels.RESULTS:Compared with the Con group,HE staining in the LPS group showed congestion and edema in renal tissues,granular or cell-like tubular patterns in the dilated tubular lu-men of renal tubules,and congestion and edema in the renal interstitium.Paller scores,Scr,serum KIM-1,IL-1β,and IL-18 levels in renal tissues were elevated(P<0.05).The expression of p-JNK,NEK7,NLRP3,and GSDMD-N also in-creased(P<0.05).Compared with the LPS group,the LPS+PF group exhibited reduced renal histopathological injury,decreased Paller score,Scr,serum KIM-1,IL-1β,and IL-18 levels(P<0.05),and decreased protein expression of p-JNK,NEK7,NLRP3,and GSDMD-N(P<0.05).Compared with the LPS+PF group,the LPS+PF+anisomycin group showed increased renal histopathological injury,Paller score,Scr,serum KIM-1,IL-1β,and IL-18 levels(P<0.05),and increased expression of p-JNK,NEK7,NLRP3,and GSDMD-N(P<0.05).CONCLUSION:Paeoniflorin may at-tenuate SA-AKI by inhibiting the JNK/NEK7/NLRP3 signaling pathway and downregulating cellular pyroptosis.

Objective:To explore the characteristics of parental emotional regulation(ER)and its influence on the ER of children with attention deficit hyperactivity disorder(ADHD).Methods:A total of 140 children with ADHD meeting the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)criteria and their parents,68 normal controls and their parents were recruited.ER was assessed using the Difficulties in Emotion Regulation Scale(DERS),Emotion Regulation Questionnaire(ERQ)and Emotion Regulation Checklist(ERC).Re-sults:Higher scores of DERS in emotion regulation strategies,impulse control and goal-directed behavior were found in parents of children with ADHD compared with parents of normal controls(Ps＜0.05).The higher emo-tional lability(EL)of ERC and lower ER of ERC detected in children with ADHD were correlated with the emo-tion regulation strategies,impulse control and goal-directed behavior of their parents(Ps＜0.01).The mediation an-alyses suggested that ER in children with ADHD may mediate the relationship of parental emotion regulation strate-gies and parental impulse control with children's EL.Conclusion:Parents of children with ADHD may exhibit emo-tional dysregulation in multiple subdimensions which might affect emotional regulation and aggravate the emotional lability of children with ADHD.