Objective:To investigate clinical and laboratory characteristics of secondary hemophagocytic lymphohistiocytosis (sHLH) associated with secondary cutaneous T-cell lymphoma (CTCL) .Methods:CTCL patients with clinically suspected sHLH were collected from Department of Hematology, Wuhan No.1 Hospital from January 2016 to October 2021, and were evaluated according to the HLH-2004 diagnostic criteria and HScore.Results:Seven CTCL patients were confirmedly diagnosed with sHLH, including 2 with primary cutaneous γδT-cell lymphoma (PC-GDTCL) , 3 with cutaneous extranodal natural killer/T-cell lymphoma (C-ENKTCL) , and 2 with primary cutaneous anaplastic large cell lymphoma (PC-ALCL) . All the 7 patients received chemotherapy, but 6 died finally, and the median overall survival duration was 26.5 days (range: 14 - 60 days) after the confirmed diagnosis of CTCL complicated by sHLH. HLH-related gene mutations, which were located in the PRF1 and LYST genes, were identified in 2 patients; lymphoma-related gene mutations were identified in the KRAS and KMT2D genes in 1 PC-GDTCL patient,and in the JAK3 and SAMHD1 genes in another PC-GDTCL patient.Conclusions:CTCL complicated by sHLH usually progresses rapidly, so early diagnosis and treatment are needed. Bone marrow biopsy and mutation screening of lymphoma- and HLH-related genes at initial diagnosis and during disease progression may facilitate early diagnosis.

Objective:To investigate the correlations of β-catenin expression with the efficacy of tyrosine kinase inhibitor (TKI) and prognosis of patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.Methods:The clinical data of 125 patients with stage Ⅲ B-Ⅳ lung adenocarcinoma who were treated with first-line EGFR-TKI treatment in the 901st Hospital of Joint Logistic Support Force of Chinese PLA from January 2016 to December 2019 were collected. The expression of β-catenin protein was detected by immunohistochemistry, and subtypes of EGFR mutations were detected by amplification refractory mutation system (ARMS). Correlations of β-catenin expression with clinicopathological features, efficacy of EGFR-TKI and prognosis were analyzed. Twenty-eight pairs of specimens were selected before EGFR-TKI treatment and after resistance to EGFR-TKI to observe the changes of β-catenin expression. Results:Among 125 advanced lung adenocarcinoma patients with EGFR mutations, there were 60 cases of EGFR 19 del, 55 cases of L858R mutation and 10 cases of rare sensitive mutation; 79 cases (63.2%) had reduced membranous expression of β-catenin, 66 cases (52.8%) had ectopic expression in cytoplasm and 28 cases (22.4%) had ectopic expression in nucleus. The positive rates of Napsin A protein in the groups with different abnormal expression patterns of β-catenin were lower than those in the corresponding normal expression groups (all P < 0.001). Patients with International Association for the Study of Lung Cancer (IASLC) grade Ⅲ showed more frequent translocation in cytoplasma and nucleus of β-catenin than patients with IASLC gradeⅠ-Ⅱ (ectopic expression in cytoplasm: χ2 = 3.99, P = 0.046,ectopic expression in nucleus: χ2 = 11.07, P = 0.001). The objective remission rate (ORR) in patients with reduced membranous expression of β-catenin and ectopic expression in nucleus was lower than that in patients with normal membranous expression ( χ2 = 4.66, P = 0.031) and negative ectopic expression in nucleus ( χ2 = 10.22, P = 0.001), and the disease control rate (DCR) in patients with ectopic expression in nucleus was lower than that in the corresponding normal expression group ( χ2 = 10.95, P = 0.001). Patients with ectopic expression of β-catenin in nucleus and cytoplasma had worse progression-free survival (PFS) and overall survival (OS) than the corresponding cytoplasmic and nuclear ectopic expression negative groups (both P < 0.05). Multivariate Cox regression analysis showed that nuclear β-catenin ectopic expression was an independent risk factor for both PFS and OS (PFS: HR = 2.088, 95% CI 1.331-3.274, P = 0.001; OS: HR = 3.656, 95% CI 1.795-7.444, P<0.001). β-catenin membranous expression was reduced in 11 of 28 tissue samples that underwent secondary biopsy compared with pre-treatment ( P = 0.049). Conclusions:β-catenin expression in advanced lung adenocarcinoma with EGFR-sensitive mutations can be used as a molecular marker to predict the efficacy of EGFR-TKI and prognosis of patients.

Objective:To investigate the effect and molecular mechanism of tumor necrosis factor-α-inducible protein 8-like 2(TIPE2)on lipopolysaccharide(LPS)or interleukin-4(IL-4)-induced phenotypic switch of adipose tissue macrophages(ATM).Methods:The expression levels of TIPE2, inducible nitric oxide synthase(iNOS), monocyte chemoattractant protein 1(MCP-1), CD206, and arginase 1(Arg-1)in the visceral adipose tissue of obese mice, TIPE2-knockout(KO)mice, and control mice were detected by immunohistochemistry, Western blotting, and real-time PCR(RT-qPCR). Peritoneal macrophages isolated from KO and wild-type mice and RAW 264.7 mouse macrophage cell line were cultured, and then stimulated with LPS(100 ng/mL)or IL-4(20 ng/mL)for 6 hours. The expression levels of TIPE2, iNOS, MCP-1, CD206, and Arg-1 were detected by Western blotting and RT-qPCR.Results:Obese mice showed down-regulated TIPE2 expression, up-regulated pro-inflammatory markers iNOS and MCP-1 expressions, and down-regulated anti-inflammatory markers CD206 and Arg-1 expressions. LPS decreased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages from mice, increased the expression of the classically activated macrophages(M1 phenotype)markers iNOS and MCP-1, and decreased the expression of the substituting activated macrophages(M2 phenotype)markers CD206 and Arg-1. IL-4 increased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages, decreased the expression of iNOS and MCP-1, and increased the expression of CD206 and Arg-1. During the M1 polarization of macrophages, LPS increased toll-like receptor(TLR4)expression as well as nuclear transcription factor κBα suppressor protein(IκBα) and NF-κB phosphorylations in macrophages. Knockout of TIPE2 further increased the expression of the TLR4/IκBα/NF-κB signaling pathway and M1 macrophage markers, and further reduced the expression of the M2 macrophage markers.Conclusion:TIPE2 regulates ATM phenotypic transformation through inhibition of the TLR4/IκBα/NF-κB signaling pathway, which ameliorates adipose tissue inflammation in obese states.

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.

Objective: To analyze the characteristics of the healthy state of TCM (Traditional Chinese Medicine) of female, and preliminarily constructs the model of TCM health status identification of female with menstrual cycle. Methods: The text of disease diagnosis and syndrome differentiation of menstrual-cycle-linked disorders from Guidelines for diagnosis and treatment of common disease of gynecology in Traditional Chinese Medicine was analyzed, and the symptoms related with viscera functions, the waxing and waning of qi and blood, and pathogenic properties were extracted. The questionnaires of diseases and syndrome elements differentiation of female by calculating the weight relationship between symptoms and health status were designed to estimate the interior state of waxing and waning of yin-yang by figuring out the different periods of menstrual, and in the last step, Constitution in Chinese medicine Questionnaire was used to identify the constitution. Through the above four identification methods, a comprehensive identification of the female's health status of TCM was formed. Results: Through the disease identification model, we distinguished the state of disease and yet disease. And through the syndrome elements differentiation model, we knew the viscera functions, the waxing and waning of qi-blood and yin-yang, and pathogenic properties. And by identifying the internal qi-blood and yin-yang status, we initially built the model that can identify health status of female integrally with the constitution. Conclusion:The model identification results can reflect the comprehensive health status of female in multiple dimensions. It can make a fine classification of women.s TCM health status. It can not only help to know the previous health status but also help to speculate the future health trend, which contributes to the formulation of personalized health interventions of follow-up.

Objective To predict and verify the upstream regulatory microRNA (miRNA)of protein kinase D1 (PKD1),and to investigate its role in cerulein induced acute pancreatitis (AP)in rats. Methods Potential up-stream regulatory miRNA of PKD1 was predicted by using bioinformatics software. Dual luciferase reporter gene system and Western blot were applied to verify the regulation of PKD1 by the selected miRNA. Experimental AP was induced by 6 intraperitoneal injection of cerulein (20 μg/ kg)at hourly intervals after administration of the CY5 - labeled notar-get control (AP group,n = 20)or selected miRNA (treatment group,n = 20),respectively by intraperitoneal injection into rats. Other rats were divided randomly into a normal control group (n = 10)without any treatment. Besides 10 rats in either AP or treatment group were sacrificed 6 hours after the first injection of cerulein,and the rats were all sacri-ficed 24 hours after the first injection. The blood samples and pancreatic tissues of each rat were collected to test serum amylase and lipase activities,or to make hematoxylin - eosin stain for AP pathological scores as well as PKD1 immuno-histochemical staining,respectively. Results TargetScan 7. 1 software analysis showed that miR - 128 - 3p was the po-tential upstream regulatory miRNA of PKD1,which was verified by dual luciferase reporter gene system and Western blot detection. Compared to the normal control group,serum amylase and lipase activities after 6 h exposure to cerulein increased in both AP group and the treatment group[13313. 00(9424. 00 - 15995. 00)U/ L,13552. 00(10399. 50 -18408. 25)U/ L vs. 1430. 50(1214. 25 - 1543. 25)U/ L;547. 00 (515. 00 - 627. 00)U/ L,857. 50(522. 00 -1222. 25)U/ L vs. 34. 00(32. 50 - 34. 75)U/ L],and the differences were significant(χ2 = 8. 715,P < 0. 05;χ2 =9. 115,P < 0. 05),which indicated that the rat models of AP were successfully established. The immunohistochemical scores of PKD1 after 24 h exposure to cerulein decreased in the treatment group[0. 50(0 - 2. 75)scores],compared with the normal control group [4. 00(4. 00 - 8. 00)scores]and the AP group [4. 00(3. 75 - 8. 00)scores],and difference was significant(χ2 = 18. 302,P < 0. 05). Accordingly,the total pathological scores of HE staining decreased significantly in the treatment group,as compared to the AP group (3. 80 ± 0. 85 vs. 6. 90 ± 1. 15,t = 4. 481,P < 0. 01). The results showed that the inflammatory cell infiltration and tissue necrosis were significantly improved after miR -128 - 3p treatment. Conclusions miR - 128 - 3p is the upstream regulatory microRNA of PKD1 which protects pan-creata from necrotic injury and inflammatory cell infiltration in PKD1 - mediated acute pancreatitis.

Objective: To evaluate the safety and efficiency of patient-controlled intravenous analgesia (PCIA) using hydromorphone supplement with dexmedetomidine on patients undergoing transcatheter arterial chemoembolization. Methods: One hundred and eighty patients, age ranged from 40 to 65 years, body mass index from 18 to 25 kg/m^2, ASA physical status Ⅱ-Ⅲ, who were scheduled for transcatheter arterial chemoembolization (TACE) under monitor anesthesia care (MAC) were randomly divided into 3 groups: hydromorphone group (H group), hydromorphone supplement with dexmedetomidine 1 μg/kg group (D1 group), hydromorphone supplement with dexmedetomidine 2 μg/kg group (D2 group), 60 patients in every group. All the groups of patients received PCIA pump, in the H group, the PCIA reagent was composed of 120 μg/kg hydromorphone and 5 mg tropisetron in 100 ml of normal saline. In comparison, PCIA regiment was composed of 120 μg/kg hydromorphone, 1 μg/kg dexmedetomidine and 5 mg tropisetron in 100 ml of normal saline in the D1 group, while 120 μg/kg hydromorphone, 2 μg/kg dexmedetomidine and 5 mg tropisetron in 100 ml of normal saline in the D2 group. The visual analogue scale (VAS) score, the observer′s assessment of alertness/sedation scale (OAA/S) score, patients′ satisfaction index, consumption of hydromorphone, the additional dose of morphine, the effective pressing times of PCIA and adverse reactions were recorded in detail at 0, 0.5, 1, 4, 12 and 24 hours after the patients underwent TACE. Results: The total consumptions of hydromorphone were (4.3±0.1), (4.1±0.1), and (3.8±0.1) mg in group H, D1, and D2, respectively, and the effective pressing times were 13±3, 6±2 and 2±1, the additional doses of morphine were (30±5), (15±3), and (3±1) mg, and adverse reaction rates were 45.0%, 28.3%, and 10.0%, respectively. The manifestations mentioned above in D2 group were significantly lower than those in group H and group D1 (P<0.05). Immediately and 5 min after embolization, at the end of surgery and 0.5, 1, 4, 12 and 24 h after surgery, the VAS scores in the D2 group were 1.9±0.2, 2.1±0.3, 1.8±0.4, 1.8±0.3, 1.7±0.3, 1.6±0.3, 1.3±0.2, 1.3±0.3, respectively, lower than those in group H and group D1 (P<0.05); The satisfaction index in D2 group at these times were 8.7±1.1, 8.9±0.8, 9.2±0.9, 9.0±0.7, 9.1±0.8, 9.0±0.6, 9.1±0.7, 9.2±0.9, respectively, higher than those in group H and group D1 (P<0.05). No breath depression happened in these three groups. Conclusion The formula of hydromorphone combined with dexmedetomidine to patients undergoing TACE is greatly safe and efficient, with advantages in alleviating pain, reducing hydromorphone consumption and the incidence of adverse reaction of hydromorphone, and without breath depression.

Objective To explore the correlation between pregnancy-related anxiety and serum 25 (OH)D level during early pregnancy. Methods A radioimmunoassay was used to determine the serum 25 (OH)D levels of 2 122 early pregnant women in Maanshan Maternal and Child Health Care Hospital, from June 2015 to 2016. Data were collected using a questionnaire. Results The mean serum 25(OH)D level was(29.71±32.27)nmol/L.About 15.2% of the subjects had adequate,22.6% had insufficient,45.1% had deficient,and 17.1% had severely deficient serum 25(OH)D levels.The type of housing and testing seasons were significantly associated with the serum 25(OH)D level.Single factor logistic regression analysis results show that pregnancy-related anxiety incidence in the group deficient in 25(OH)D was higher than that in the adequate group, which has a statistically significant difference (P<0.05). After adjusting for the maternal age,BMI,and educational level,multivariate logistic regression analysis results showed that the difference was statistically significant. Conclusion The serum 25(OH)D level in early pregnant women was inadequate. Furthermore, lack of serum 25(OH)D in early pregnancy and pregnancy-related anxiety were negatively correlated.

Objective To evaluate the effect of comprehensive intervention on perioperative antimicrobial prophy-laxis in clean incision surgery in a hospital.Methods From 2011 ,clean incision surgery cases were performed com-prehensive intervention,antimicrobial use in 2011 -2013 were compared.Results A total of 5 945 cases of clean in-cision surgeries were investigated between 2011 and 2013,3 827 cases (64.37%)received prophylactic use of anti-microbial agents.Prophylactic antimicrobial usage rates in 2011 -2013 were 84.95%,69.99%,and 52.97% re-spectively(χ2 =380.94,P <0.001);the correct rates of medication time were 50.97%,79.99%,and 98.95% re-spectively(χ2 =827.02,P <0.001 );the percentages of prophylactic antimicrobial use ≤24 hours were 24.91 %, 39.96%,and 64.95% respectively(χ2 =422.55,P <0.001 );additional antimicrobial usage rates during surgery were 50.00%,60.00%,and 80.00% respectively(χ2 =59.47,P <0.001 ).Conclusion The implementation of comprehensive intervention measures can standardize antimicrobial use,reduce prophylactic antimicrobial usage rate,improve the correct rate of medication time,shorten the duration of antimicrobial use,and implement addition-al use of antimicrobial agents during surgery.

Objective To investigate the expression of sal-like 4 (SALL4) in tissues of primary hepatocellular carcinoma (HCC) and its association with epithelial-mesenchymal transition (EMT) and clinicopathological characteristics.Methods Immunohistochemistry and nucleic acid in situ hybridization were used to measure the mRNA expression of SALL4,epithelial cadherin (E-cadherin),vimentin,and Snail in 72 HCC samples,2 fetal liver samples,and 2 normal adult liver tissue samples.Results Strong expression of SALL4 was observed in hepatoblasts in fetal liver,but SALL4 expression was not observed in primitive hematopoietic cells and normal adult hepatocytes or biliary epithelial cells.In the HCC samples,the positive rate of SALL4 was 47.2％ (34/72),showing focal positive nuclear staining.The HCC patients with microscopic microvascular tumor thrombus and portal vein tumor thrombus,a serum alpha-fetoprotein level of ≥ 350 ng/ml,International Union Against Cancer (UICC) stage Ⅲ+Ⅳ,and an age of ＜ 46 years showed higher positive expression of SALL4 than those with no microscopic microvascular tumor thrombus or portal vein tumor thrombus,a serum alpha-fetoprotein level of＜ 350 ng/ml,UICC stage Ⅰ+Ⅱ,and an age of ≥ 46 years.The HCC patients with positive SALL4 showed lower postoperative disease-firee survival rate and overall survival rate than those with negative SALL4 (P ＜ 0.05).Sixty percent of the patients with microvascular tumor thrombus (21/35) showed positive expression of SALL4.The positive rate of SALL4 was negatively correlated with E-cadherin (r =-0.434,P ＜ 0.01),but positively correlated with vimentin and Snail (vimentin:r =0.516,P ＜ 0.01;Snail:r =0.571,P ＜ 0.01).Conclusion In patients with primary HCC,the expression of SALL4 greatly affects EMT,which helps with the research on invasion and metastasis of liver cancer and prognostic evaluation.