OBJECTIVE To investigate the reference range of tacrolimus blood concentration in children with Henoch- Schonlein purpura nephritis （HSPN） and analyze the factors affecting the blood concentration， in order to provide a reference for rational use of the drug in clinic. METHODS Clinical data of children with HSPN who were treated with tacrolimus and regularly monitored for blood concentration at the Children’s Hospital Affiliated to Kunming Medical University were retrospectively collected from January 2018 to January 2024. The threshold of effective concentration of tacrolimus was determined by the receiver operating characteristic curve of the subjects. The clinical efficacy of tacrolimus in different concentrations and the incidence of adverse drug reaction （ADR） were compared to determine the reference range of tacrolimus blood concentration. The factors influencing the blood concentration were analyzed by one-way and multiple linear regression. RESULTS A total of 97 pediatric patients were included， and their tacrolimus blood concentrations were monitored 203 times， the blood concentration was 4.26 （2.47， 6.34） ng/mL. The area under the receiver operating characteristic curve of the subjects was 0.723 （95%CI：0.596-0.850， P＜ 0.01）， which corresponded to an effective threshold of 2.19 ng/mL. The clinical efficacy in pediatric patients with tacrolimus blood concentrations of 3-＜5 ng/mL， 5-＜10 ng/mL， and ≥10 ng/mL was significantly higher than that of children with concentrations ＜3 ng/mL （P＜0.05）. Additionally， the overall incidence of ADR in children with concentrations of 5-＜10 ng/mL and ≥10 ng/mL was significantly higher than that in children with concentrations ＜3 ng/mL and 3-＜5 ng/mL （P＜0.05）. The impact of body mass index and CYP3A5 genotype on the blood concentration of tacrolimus was statistically significant （P＜0.05）. CONCLUSIONS When using tacrolimus to treat HSPN in children clinically， the reference range for blood concentration is 3 to 5 ng/mL； body mass index and CYP3A5 genotype are factors that influence the blood concentration of tacrolimus.

Background Asthma poses a serious threat to children's growth, development, and mental health, thus there has been an increasing focus on the control of asthma morbidity in children and the assessment of its risk factors. A growing body of research has found that exposure to ambient air pollutants an significatly increase the risk of childhood asthma. Objective To understand the changes of ambient air pollutant concentrations in Nanjing and asthma outpatient visits to Nanjing Children's Hospital, and to quantitatively analyze the effects of exposure to different ambient air pollutants on children's asthma outpatient visits. Methods Daily data of ambient air pollutants fine particulate matter (PM_2.5), inhalable particle (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), ozone (O₃), meteorological factors (air temperature & relative humidity), and outpatient visits due to asthma in the hospital from January 1, 2019 to December 31, 2023 were collected, and a generalized additive model based on quasi poisson distributions was used to quantitatively analyze the short-term effects of ambient air pollutant exposure on outpatient visits due to asthma in the hospital. Results The annual average concentrations of PM_2.5, PM₁₀, SO₂, and NO₂ in Nanjing from 2019 to 2023 did not exceed the national limits. For single-day lagged effects, the single-pollutant model showed that the effects of PM_2.5, PM₁₀, NO₂, and CO on children's asthma outpatient visits were greatest for every 10 units increase at lag0, with excess risk (ER) of 1.39% (95%CI: 0.65%, 2.14%), 1.46% (95%CI: 0.97%, 1.95%), 5.46% (95%CI: 4.36%, 6.57%), and 0.18% (95%CI: 0.11%, 0.26%), respectively, and SO₂ reached the maximum effect at lag1, with an ER of 23.15% (95%CI: 13.57%, 33.53%) for each 10 units increase in concentration. Different pollutants reached their maximum cumulative lag effects at different time. The PM₁₀, PM_2.5, SO₂, NO₂, and CO showed the largest cumulative lag effects at lag01, lag01, lag02, lag02, and lag03, respectively, with ERs of 1.35% (95%CI: 0.77%, 1.92%), 0.96% (95%CI: 0.10%, 1.83%), 28.50% (95%CI: 15.49%, 42.98%), 6.92% (95%CI: 5.53%, 8.33%), and 0.31% (95%CI: 0.20%, 0.42%), respectively. The influences of PM_2.5 and PM₁₀ on outpatient visits due to asthma in the hospital became more pronounced with advancing age, while the associations with NO₂, SO₂, and CO were weakened as children grew older. Conclusion Ambient air pollutants (PM_2.5, PM₁₀, SO₂, NO₂, CO) can increase childhood asthma visits, and different pollutants have varied effects on the number of asthmatic children's visits at different ages.

OBJECTIVE To prepare C-phycocyanin nanoparticles （CPC-NPs） and evaluate the in vitro mechanism of CPC- NPs on acute lung injury induced by lipopolysaccharide （LPS） combined with seawater. METHODS Ion crosslinking method was used to prepare CPC-NPs using CPC as the drug， carboxymethyl chitosan （CMCS） as the carrier， and CaCl2 as the crosslinking agent. The basic characterization of CPC-NPs was carried out. Mouse alveolar type Ⅱ epithelial cells MLE-12 and macrophages RAW264.7 were divided into 7 groups： normal group （Con group）， model group （Mod group）， blank NPs group， CPC-NPs 30， 60， 120 and 240 μg/mL groups. Except for the Con group， all other groups were treated with a combination of 10 μg/mL LPS and 25% seawater for 6 hours. After modeling， each treatment group was treated with corresponding drugs for 24 hours. The levels of malondialdehyde （MDA）， total antioxidant capacity （T-AOC）， superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） in MLE-12 cells， as well as the expression levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， caspase-3 protein and mRNA， CAT and glutathione S-transferase （GST） mRNA were determined. The levels of interleukin- 1β （IL-1β）， tumor necrosis factor-α （TNF-α） and IL-6 in RAW264.7 cells， as well as the expression levels of NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， cleaved caspase-1 protein， and mRNA expressions of IL-1β，TNF-α， IL-6 and inducible nitric oxide synthase （iNOS） were all detected. RESULTS The prepared CPC-NPs had particle size of （675.69±64.58） nm， Zeta potential of （－20.11± E-mail：zhangleifang1986@163.com 0.98） mV， polydispersity coefficient of 0.455±0.010 （n＝3）；entrapment efficiency of 35.60%， and drug loading of 16.13%；CPC-NPs had regular spherical shapes， where the drug could be sustainably released for more than 30 hours. Compared with Mod group， the levels of T-AOC， SOD， CAT （excluding the 30 μg/mL group of CPC-NPs） and GSH-Px， mRNA expressions of CAT and GST， as well as the Bcl-2/Bax protein ratio and mRNA ratio were significantly increased in MLE-12 cells of different concentration groups of CPC-NPs， while MDA levels and caspase-3 protein and mRNA expression were significantly reduced （P＜0.01 or P＜0.05）. Compared with Mod group， the levels of IL-1β， TNF-α and IL-6， NLRP3 and cleaved-caspase-1 protein expressions， as well as the mRNA expressions of IL-1β， TNF-α， IL-6 and iNOS in RAW264.7 cells of different concentration groups of CPC-NPs were significantly reduced （P＜0.01 or P＜0.05）. CONCLUSIONS CPC-NPs with lung targeting and sustained release property were prepared successfully， which can alleviate acute lung injury induced by LPS combined with seawater through antioxidant stress， inhibiting cell apoptosis and inflammatory response.

Objective To study the possibility of using cone-beam computed tomography(CBCT)with CTAn software to analyze bone resistance during mandibular third molar extraction surgery.Methods Fifty-three patients who underwent CBCT scans for third molars at the Department of Stomatology from January 1st 2021 to July 31th 2023 were induded,involving a total of 91 mandibular third mo-lars.CTAn software was used to analyze the buccal and lingual bone volume regions around mandibular third molars in CBCT images,assessing three-dimensional bone microstructural parameters.Results Significant differences(P＜0.05)in tissue volume,trabecular bone volume/tissue volume,bone surface/trabecular bone volume,bone surface/tissue volume,and bone mineral density between the buccal and lingual bone volume areas were observed in both the total sample and in stratified analyses based on themesially inclined/verticalmandibular third molar impactionand gender.In high/mid-level mesially inclined and vertical impactions,females showed more significant differences in microstructural parameters of the buccal and lingual bone volume compared to males.Conclusion The inte-gration of CBCT with CTAn software offers a viable method for assessing bone resistance during mandibular third molar extractions.Lin-gual bone exhibits greater bone tissue content,denser trabeculae with smaller tissue volume compared to buccal bone.During mandibu-lar third molar extraction,compressing the buccal alveolar bone helps create trabecular compression space more easily.Additionally,the buccal alveolar bone is more amenable to grinding than the lingual side,thereby achieving a reasonable buccal dislocation of root.For female patients with high/mid-level mesially inclined and vertical impactions of the mandibular third molars,a buccal approach is more advisable to be followed.The evaluation of bone microstructural parameters and accurate determination of bone resistance offer valuable insights for the minimally invasive removal of impacted teeth.

Objective:To investigate the clinicopathological characteristics of oxyntic gland adenoma(OGA)and gastric adenocarcinoma of the fundic gland type(GA-FG).Methods:Six cases of fundic gland-type tumors(three OGA and three GA-FG)diagnosed at the Fujian Cancer Hospital between August 2020 and February 2023 were retrospectively analyzed.The clinical data,endoscopic features,pathological charac-teristics,immunohistochemical results,treatment,and prognosis were analyzed.Results:Six patients with an average age of 57 years,in-cluding one male and five females,were mainly affected in the gastric fundus and body,with the superficial elevated type being the most common.The pathological features of gastric gland-type tumors are mostly located in the deep layer of the gastric mucosa,showing a dis-ordered glandular structure mainly composed of chief cell-type cells.There were three cases of OGA and three cases of GA-FG.Immunohis-tochemical results showed that pepsinogen 1 was positive in five cases,mucin 6(MUC6)in five cases,synaptophysin(Syn)in six cases,chro-mogranin(CgA)was negative in all cases,and Ki-67 was less than 10%.Conclusions:The incidences of OGA and GA-FG are low,and there is no obvious endoscopic specificity.Endoscopy physicians have an insufficient understanding,which can easily lead to misdiagnoses and missed diagnoses.Immunohistochemistry is helpful for the differential diagnosis,and endoscopic mucosal resection or stripping is the pre-ferred treatment option.

Objective To find out the prevalence of antiretroviral therapy(ART)drugs among treponema pallidum(TP)antibody(anti-TP)positive blood donors in Shenzhen,and to assess the blood safety risks brought about by the new trends of human immunodeficiency virus(HIV)diagnosis and treatment.Methods A stratified random sampling method was used to select 60 repeat blood donors(negative control group)who passed blood screening in Shenzhen from March 2019 to January 2023,and 3 people who regularly took known ART drugs were named positive control group,358 anti-TP positive/anti-HIV negative blood do-nors were named experimental group 1,20 anti-TP positive/anti-HIV positive blood donors were named ex-perimental group 2.The liquid chromatography-mass spectrometry(HPLC-MS/MS)was applied to detect the concentration of 8 ART drugs in plasma samples of each group,and the use of ART drugs was analyzed.Re-sults After the positive control group's plasma was diluted with a 1:6 dilution mixture,the ART drugs could still be detected.The positive mixed plasma samples of 1:6 people in Group 1 and Group 2 were split and validation,one ART drug positive sample was detected in Group 2,which was positive for anti-HIV,pro-tein immunoblotting,and HIV RNA.The detection rate of ART drugs in anti-TP positive blood donors was 0.26％,0.00％in Group 1 and 4.00％in Group 2.Conclusion The use of ART drugs has been found among anti-TP positive blood donors in Shenzhen,and people with HIV infection and high-risk sexual behavior are more likely to use antiretroviral drugs.

Objective:To explore the effectiveness and safety of autologous fat granule transplantation for facial rejuvenation.Methods:Databases including PubMed, Cochrane Library, Google Scholar, Web of Science, China Biology Medicine Database, Wanfang Database, and CNKI were searched. The search time range was from 2013 to 2023. Search key words included autologous fat transplantation, facial rejuvenation, efficacy, effectiveness, safety, complications, etc. Meta-analysis was used. Literature search was conducted by using tool method and forward search method. OR (95% CI) was used as the statistical measure for efficacy analysis. Heterogeneity of literature was tested by I2 test. Publication bias was tested by Begg′ s test. Results:A total of 23 literatures were included, covering 2 852 beauty seekers. There was no significant publication bias. The satisfactory rate of beauty seekers after autologous granular fat transplantation was relatively high ( OR=0.95, 95% CI: 0.91-0.97). The success rate of one-time injection was relatively high ( OR=0.79, 95% CI: 0.73-0.84). The incidence of postoperative complications was relatively low ( OR=0.02, 95% CI: 0.01-0.04). Conclusion:Autologous fat granule transplantation surgery has good effectiveness and safety for facial rejuvenation.

Objective To investigate the effect and mechanism of emodin on focal cerebral ischemia in rats based on myeloid differentiation factor 88(MyD88)/extracellular signal-regulated kinase(ERK)pathway and nuclear factor-κB(NF-κB)nuclear translocation.Methods SD rats were randomly divided into sham operation group,model group and emodin group,with six rats in each group.The rat model of transient middle cerebral artery occlusion(tMCAO)was established by middle cerebral artery embolization.Rats in the emodin group were given 40 mg·kg-1 emodin by gavage for three times at 72,48 and 24 hours before modeling.At 24 hours after modeling,the neurological function of rats was scored.TTC staining was used to detect the area of cerebral infarction.HE staining was used to observe the morphological changes of brain tissue.The mRNA expression levels of MyD88 and tumor necrosis factor-α(TNF-α)in brain tissue were detected by RT-qPCR.The expression levels of MyD88,ERK,p-ERK and TNF-α in brain tissue were detected by Western Blot.The protein expression of NF-κB in brain tissue was detected by immunofluorescence.Results Compared with the sham operation group,the neurological function score of the model group was significantly increased(P＜0.01),and the cerebral infarction area was significantly increased(P＜0.01).In the cortical area of the ischemic penumbra,cell necrosis,abnormal cell morphology,nuclear fragmentation and atrophy,and the number of cells decreased significantly;the mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly increased(P＜0.01,P＜0.001),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly increased(P＜0.05,P＜0.01,P＜0.001),and the proportion of NF-κB into nuclear cells was significantly increased(P＜0.001).Compared with the model group,the neurological function score of rats in the emodin group was significantly decreased(P＜0.05),and the area of cerebral infarction was significantly reduced(P＜0.05).The number and morphology of neurons in the ischemic penumbra cortex were restored to a certain extent.The mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly decreased(P＜0.05,P＜0.01),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly decreased(P＜0.05),and the proportion of NF-κB into nuclear cells was significantly decreased(P＜0.001).Conclusion Emodin has a preventive and protective effect on rats with focal cerebral ischemia,which may be related to its inhibition of MyD88 activation,ERK phosphorylation and NF-κB nuclear translocation,and then down-regulation of inflammatory cascades and secretion of pro-inflammatory factors such as TNF-α,thereby exerting anti-inflammatory effects.

OBJECTIVE: To explore the prognostic value of early multiple detection indicators in combination with sequential organ failure assessment (SOFA) in sepsis patients. METHODS: A retrospective analysis was conducted. Patients with sepsis admitted to the department of critical care medicine of Huanggang Central Hospital of Yangtze University from May 2020 to May 2022 were selected as the research subjects. Coagulation indicators, inflammatory factors, blood routine, liver and kidney function, and blood gas analysis were collected at admission. Organ dysfunction was assessed based on the SOFA score within 24 hours after admission. Patients were divided into a survival group and a death group according to the outcome of 28 days in ICU. Differences in the above indicators between the two groups were compared. Multifactorial Logistic regression analysis was used to analyze prognostic factors of 28-day mortality in sepsis patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive performance of various indicators, the SOFA score, and the combine model for the 28-day outcome in patients with sepsis. RESULTS: A total of 101 patients with sepsis were enrolled, 56 patients survived and 45 patients died. Compared to the survival group, patients in the death group were older, the proportion of patients with septic shock was larger, the SOFA score, and the proportion of pulmonary infection were higher, the prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged, the prothrombin activity (PTA) was significantly shortened, and antithrombin (AT) was significantly decreased, the levels of hypersensitivity C-reactive protein (hs-CRP), blood urea nitrogen (BUN), total bilirubin (TBil), and lactic acid (Lac) were significantly increased, while the platelet count (PLT) was significantly decreased. Multifactorial Logistic regression analysis showed that pulmonary infection [odds ratio (OR) = 0.010, 95% confidence interval (95%CI) was 0.001-0.164, P = 0.001], AT (OR = 0.944, 95%CI was 0.910-0.978, P = 0.002), hs-CRP (OR = 1.008, 95%CI was 1.001-1.015, P = 0.017), Lac (OR = 1.619, 95%CI was 1.195-2.193, P = 0.002), and SOFA score (OR = 1.363, 95%CI was 1.076-1.727, P = 0.010) were independent prognostic factors for 28-day mortality in patients. A combined model was constructed using pulmonary infection, AT, hs-CRP, Lac, and SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) for the combine model in predicting sepsis prognosis was 0.936 (95%CI was 0.869-0.975, P < 0.001), which was higher in value compared to single indicators (AUC of AT, hs-CRP, Lac, and SOFA score were 0.775, 0.666, 0.802, 0.796, respectively, all P < 0.05). CONCLUSIONS The predictive ability of the SOFA score for sepsis patient outcomes is limited. The combine model combining infection site, AT, hs-CRP, and Lac shows better predictive ability.
Humans ; Organ Dysfunction Scores ; Retrospective Studies ; C-Reactive Protein ; ROC Curve ; Sepsis/metabolism* ; Prognosis ; Anticoagulants ; Antithrombin III ; Intensive Care Units

ObjectiveTo investigate the therapeutic effect of the water extract of Zanthoxylum bungeanum aqueous extract（ZBAE）on rheumatoid arthritis. MethodThe sixty SD rats were divided into normal group， model group ［complete Freund's adjuvant （CFA）， 10 mg·kg^-1］， methotrexate（MTX） group （0.25 mg·kg^-1）， low -， medium -， and high-dose ZBAE groups （90， 180， 360 mg·kg^-1）. The rats in MTX group were given intraperitoneal injection for two weeks， three times a week， and the rats in ZBAE group were administrated for 14 days. The swelling of the ankle joint and body weight were observed， and arthritis scores were also performed. Computed tomography （CT）， hematoxylin-eosin （HE） staining and safranine-O and fast green staining were used to observe the effect of ZBAE on synovial hyperplasia and bone protection. Cell counting kit-8（CCK-8）method was used to detect the proliferation of the RA-FLSs cells treated with ZBAE. According to the results of CCK-8 experiment， the optimal concentration and time of administration were determined， blank group， low -， medium -， and high-dose ZBAE groups （0.08，0.10，0.12 g·L^-1） were set up. The cell cycle distribution and apoptosis rate were analyzed by flow cytometry，the migration ability of RA-FLSs cells was examined by scratch test. Western blot was used to detect the effect of ZBAE on phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， cyclin-dependent kinase 2 （CDK2）， Cyclin A and phosphorylated PI3K， Akt （p-PI3K，p-Akt） protein expression in RA-FLSs cells. ResultCompared with the normal group，joint swelling index and arthritis score were increased in the model group （P<0.05），the bone of the ankle was seriously damaged， and there was obvious synovial hyperplasia. Compared with the model group， the ZBAE group could significantly reduce the joint swelling index （P<0.05）， inhibit synovial hyperplasia and cartilage destruction. In vitro study showed that compared with the blank group， ZBAE could inhibit the migration of RA-FLSs （P<0.05）， promoted cell apoptosis （P<0.05）， and acted on RA-FLSs cells in S phase to inhibit cell proliferation. Moreover， the result of Western blot showed that compared with the blank group， the expression of p-PI3K， p-Akt， CDK2 and Cyclin A proteins were significantly decreased in the high dose group of ZBAE （P<0.05）. ConclusionThese results suggest that ZBAE has a therapeutic effect on rheumatoid arthritis by inhibiting synovial hyperplasia， promoting synovial apoptosis and inhibiting its migration.