Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review

SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.

Epidemiological investigation of an outbreak of anthrax in Gongliu County, Xinjiang Uygur Autonomous Region / 预防医学

Abstract@#A suspected case of cutaneous anthrax was reported by Gongliu County Disease Control and Prevention Center, Ili Kazak Autonomous Prefecture, Xinjiang Uygur Autonomous Region on August 19, 2021. Then, an epidemiological survey was performed by a joint investigation team consisting of professionals from Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention, intermediate-level trainees from the Field Epidemiology Training Program of Chinese Center for Disease Control and Prevention, and professionals from Ili Kazak Autonomous Prefecture Center for Disease Control and Prevention. A total of 11 cutaneous anthrax cases were identified, including 8 suspected cases and 3 clinically diagnosed cases, and all cases were villagers in Y Village, X Township, Gongliu County, without severe case or deaths found. The onset of the first case occurred on July 27, and the onset of the last case occurred on August 16. The main clinical manifestations included ulcerative eschar on hands and exposed skin of the upper extremity. A Bacillus anthracis isolate was detected in meat samples from infected cattle. Epidemiological surveys showed that villagers did not report infected cattle to related sectors and privately slaughtered and ate meat from infected cattle without any effective protective measures, resulting in this outbreak. It is recommended to strengthen health education for people raising, selling and slaughtering livestock, and publicize zoonotic disease control knowledge, including anthrax, and establish an effective surveillance and response system for anthrax for immediate identification and treatment of epidemics.

Meta-analysis of infection and disease among household contacts of patients with drug-resistant tuberculosis / 中国热带医学

@#Abstract: Objective　To analyze the association between drug resistance and the risk of latent tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis, and to explore whether the compensatory mutation of drug-resistant Mycobacterium tuberculosis will enhance its pathogenicity or transmission ability. Methods　The English and Chinese databases, including PubMed, web of science, EMBASE, Cochrane library database, CNKI and Wanfang database, were searched by computer from the time of establishment of the database to January 2022. Cohort studies on the risk of infection and disease among household contacts of patients with drug-resistant and sensitive pulmonary tuberculosis were searched and screened according to the inclusion and exclusion criteria. The data were extracted and evaluated by NOS scale, using stata16.0 software meta-analysis to calculate the combined effect of tuberculosis infection and disease risk of family contacts, and carry out heterogeneity test, subgroup analysis and sensitivity analysis. Results　A total of 7 cohort studies involving 9653 TB index cases and 29, 734 house contacts were included. The results of meta-analysis showed that compared with drug-sensitive pulmonary tuberculosis patients, the risk of tuberculosis infection in house contacts of drug-resistant pulmonary tuberculosis patients was increased (OR=1.56, 95%CI=1.25-1.96, P<0.001), but there was no difference in the risk of incidence (RR=1.06, 95%CI=0.80-1.41, P=0.67>0.05). Subgroup analysis showed that the risk of latent tuberculosis infection in house contacts was affected by the study area, and the size of family contacts had an impact on the risk of TB . Sensitivity analysis showed that the results of meta-analysis were robust. Conclusion　Compared with drug sensitive TB patients, household contacts with drug-resistant TB patients had a higher risk of tuberculosis, but there was no difference in the risk of TB among the two groups.

LINC01018 regulates the proliferation, apoptosis and radiosensitivity of gastric cancer HGC-27 cells through miR-297 / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨长基因间非编码RNA（long intergene non-coding RNA，LINC）01018是否通过抑制miR-297调控胃癌HGC-27细胞的增殖、凋亡及放射敏感性。方法： 收集于青海省第五人民医院接受手术的胃癌患者（21例）及化疗抵抗胃癌患者（19例）的癌组织和癌旁组织，以qPCR检测胃癌组织、化疗抵抗胃癌组织和胃癌HGC-27细胞中LINC01018、miR-297的表达。双荧光素酶报告基因实验验证LINC01018与miR-297之间的靶向关系。在HGC-27细胞中转染LINC01018过表达质粒pcDNA-LINC01018或miR-297抑制剂，或共转染pcDNA-LINC01018和miR-297模拟物，以qPCR检测验证细胞转染效果。MTT和克隆形成实验检测转染后HGC-27细胞的增殖活力与克隆形成能力，流式细胞术检测转染后HGC-27细胞的凋亡率，克隆形成实验检测各组转染后HGC-27细胞的放射敏感性，WB实验检测细胞中Ki67、cleaved-caspase3、pro-caspase3蛋白的表达。结果： 与癌旁组织或胃正常黏膜上皮细胞GES-1相比，胃癌组织、化疗抵抗胃癌组织和胃癌HGC-27细胞中LINC01018呈低表达、miR-297呈高表达（均P<0.01）。LINC01018与miR-297存在靶向结合关系，LINC01018负向调控miR-297的表达。过表达LINC01018或敲减miR-297可抑制HGC-27细胞的增殖活力与克隆形成能力、降低细胞存活率，促进细胞的凋亡、下调Ki67和pro-caspase3蛋白表达水平、上调cleaved-caspase3蛋白表达水平、提高HGC-27细胞的放射敏感性（均P<0.01）。共转染pcDNA-LINC01018和miR-297模拟物可逆转过表达LINC01018对HGC-27细胞的所有上述作用，尤其可逆转其对HGC-27细胞的放射增敏作用（P<0.05或P<0.01）。结论： LINC01018通过下调miR-297表达抑制胃癌HGC-27细胞增殖而促进凋亡和增强细胞的放射敏感性，该作用与Ki67和caspase3的表达变化有关。

Expression and Clinical Significance of PD-L1 and MicroRNA-138-5p in Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of PD-L1 and microRNA-138-5p in the peripheral blood mononuclear cells of patients with acute myeloid leukemia.@*METHODS@#The SYBR GreenⅠreal-time PCR was used to detect the expression levels of PD-L1 mRNA and miR-138 in 20 cases of primary AML, 9 cases of relapsed/refractory AML and 8 cases of complete remission. The samples of peripheral blood of 20 healthy peoples were used as controls.@*RESULTS@#The expression levels of PD-L1 in both the primary AML and the relapsed/refractory AML groups were significantly higher than those in the healthy control group (P0.05). and there was a negative correlation between PD-L1 mRNA and miR-138 in primary AML patients (P<0.05).@*CONCLUSION@#The expression of PD-L1 increases and the expression of miR-138 down-regulates in PBMNCs of AML patients, furthermore, both correlate each other.

Evaluation of diagnostic scores for acute appendicitis

Objective: To assess the sensitivity of the Alvarado score [AS], modified Alvarado score [MAS], Fenyo-Lindberg score [FS], Lintula score [LS], Eskelinen score [ES], Teicher score [TS], and Christian score [CS] [seven scorings] in patients with acute appendicitis [AA]

Study Design: Analytical study

Place and Duration of Study: The First Affiliated Hospital of Chongqing Medical University, China, from January 2012 to June 2015

Methodology: Patients with diagnosis of AA were evaluated retrospectively to compare the scoring systems. The diagnostic sensitivity [the correct number of diagnoses divided by the total number] was compared. Data were analyzed using SPSS software

Results: One hundred and seventy-nine patients were studied. The sensitivity of AS was 92.7%; It outperformed each of the other scores. The sensitivity of FS, LS, and TS in women was lower than that in men [p=0.016, p<0.001, and p<0.001, respectively]. The sensitivity of the FS, ES, TS, and CS in patients with a duration of illness greater than 48 hours was lower than that in patients with a duration of illness less than 48 hours [p<0.001 for all]

Conclusion: AS is the most useful and sensitive diagnostic tool for AA. FS, LS, and TS had a lower diagnostic sensitivity in women; and FS, ES, TS, and CS had a low sensitivity in patients with a duration of illness greater than 48 hours

Effect of IL-34 on malignant biological behavior of human acute monocytic leukemia cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective： ：To study the effects of IL-34 over-expression on malignant biological behavior of acute monocytic leukemia (AMoL) cells. Methods: The lentiviral vector pCDH-GFP for over-expressing IL-34 was constructed and infected into AMoL cell lines (THP1 and MOLM-13). Then its effects on proliferation, colony forming and cell cycle as well as apoptosis were tested by the MTS, colony formation assay and Annexin-V/PI staining, respectively. The cell differentiation phenotypes were assessed by fflow cytometry. Nude mice xenograft model was established to observe the tumor size and mass as well as the macrophages recruitment. Results: qPCR analysis showed that the expression of IL-34 mRNAin THP1-IL-34 and MOLM-13-IL-34 cells was nearly 4 000 and 3 000 folds higher than their respective control cells (all P<0.01), indicating that AMoL cell lines over-expressing IL-34 were successfully established. In vitro study showed that over-expression of IL-34 in AMoL cell lines promoted their proliferation potential(72 h:[0.738±0.003] vs [0.646±0.008]; [0.290±0.004] vs [0.247±0.004]; all P<0.01) and colony formation ([127.00 ± 3.37] vs [86.00±4.08]; [160.70±4.70] vs [116.70±3.93]; all P<0.01), whereas had little effect on apoptosis (all P>0.05). Over-expression of IL-34 promotedAMoLcell differentiation towards monocyte-macrophage lineage as the expressions of the monocyte-macrophage markers, CD11b and CD14, were increased whereas the expression of immature marker, CD71, was decreased in AMoL cell lines over-expressing IL-34(all P<0.05). Nude mice xenograft model showed that IL-34 over-expression stimulated macrophage recruitment in tumor tissues (P<0.01). Conclusion: Over-expression of IL-34 in human AMoL cell lines promotes their proliferation, colony forming potential and differentiation towards monocyte-macrophage lineage. Furthermore, IL-34 participates in the process of macrophages recruitment in vivo.

clinical research for Ganoderanfs effect on preventing and treating cerebral arteriosclerosis through inhibiting NADPH oxidizing enzyme expression

A lot of researches have verified that produced excessive reactive oxygen is one of the hazard factors causing atherosclerosis. NADPH oxidase is the main protease of vascular cell's producing reactive oxygen, the expression of its relevant subunits is closely correlated with the occurring and development process of atherosclerosis

Oxidizing reaction could damage organism tissue cells, ganoderan has very significant effect on the anti-oxidizing function of cell

The pharmaceutical research of ganoderan has significant meaning in curing diabetes mellitus, preventing and controlling arteriosclerosis. This paper is mainly to discuss the effect of anoderan's inhibiting NADPH oxidizing enzyme expression on preventing and treating cerebral arteriosclerosis and its action mechanism

Remote preconditioning, perconditioning, and postconditioning: a comparative study of their cardio-protective properties in rat models

OBJECTIVE: Ischemia reperfusion injury is partly responsible for the high mortality associated with induced myocardial injury and the reduction in the full benefit of myocardial reperfusion. Remote ischemic preconditioning, perconditioning, and postconditioning have all been shown to be cardioprotective. However, it is still unknown which one is the most beneficial. To examine this issue, we used adult male Wistar rat ischemia reperfusion models to compare the cardioprotective effect of these three approaches applied on double-sided hind limbs. METHODS: The rats were randomly distributed to the following five groups: sham, ischemia reperfusion, remote preconditioning, remote perconditioning, and remote post-conditioning. The ischemia/reperfusion model was established by sternotomy followed by a 30-min ligation of the left coronary artery and a subsequent 3-h reperfusion. Remote conditioning was induced with three 5-min ischemia/5-min reperfusion cycles of the double-sided hind limbs using a tourniquet. RESULTS: A lower early reperfusion arrhythmia score (1.50 + 0.97) was found in the rats treated with remote perconditioning compared to those in the ischemia reperfusion group (2.33 + 0.71). Meanwhile, reduced infarct size was also observed (15.27 + 5.19% in remote perconditioning, 14.53 + 3.45% in remote preconditioning, and 19.84+5.85% in remote post-conditioning vs. 34.47 + 7.13% in ischemia reperfusion, p<0.05), as well as higher expression levels of the apoptosis-relevant protein Bcl-2/Bax following global (ischemia/reperfusion) injury in in vivo rat heart models (1.255 + 0.053 in remote perconditioning, 1.463 + 0.290 in remote preconditioning, and 1.461 +0.541 in remote post-conditioning vs. 1.003 + 0.159 in ischemia reperfusion, p<0.05). CONCLUSION: Three remote conditioning strategies implemented with episodes of double-sided hind limb ischemia/reperfusion have similar therapeutic potential for cardiac ischemia/reperfusion injury, and remote perconditioning has a greater ability to prevent reperfusion arrhythmia.

Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

The pharmacokinetics (PK) of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg) and a multiple oral dose (90 mg d-1×6 d) administration. The effect of food on the PK of one single oral dose (360 mg) was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0). All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064) of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters.

Embora a farmacocinética (PK) do cloridrato de diltiazem nas formas de comprimidos de liberação imediata e cápsulas de liberação modificada em ensaios clínicos já tenha sido relatada, a pesquisa da PK do cloridrato de diltiazem na forma de cápsulas com peletes de liberação retardada e sustentada ainda é muito importante. Neste trabalho, propusemos avaliar a farmacocinética do cloridrato de diltiazem administrado através desta nova forma farmacêutica em voluntários chineses sadios, assim como a influência da ingestão de alimentos neste perfil farmacocinético. Foi realizado um ensaio clínico aberto, randomizado e paralelo em 36 voluntários, que receberam dose oral única de 90 mg, 180 mg ou 270 mg e dose múltiplas (90 mg/d × 6 d) pela mesma via de administração. Para avaliar o efeito da ingestão de alimentos sobre a PK do diltiazem foi realizada a administração de dose única (360 mg) em 24 voluntários chineses sadios. A concentração plasmática do diltiazem foi determinada por Cromatografia Liquida de Alta Eficiência em fase reversa (CLAE-FR) e os principais parâmetros farmacocinéticos foram analisados através do emprego do software PKSolver (Ver 2.0). O ensaio de farmacocinética clínica foi conduzido na clínica Pharmacological Center (No.JDX1999064) do Hospital de Xiangya, Central South University, China. Os parâmetros PK obtidos indicaram que a nova formulação de cápsulas de liberação retardada e sustentada de cloridrato de diltiazem possue marcantes características de liberação retardada e controlada do fármaco.

The increased but non-predominant expression of Th17- and Th1-specific cytokines in Hashimoto’s thyroiditis but not in Graves’ disease

Hashimoto’s thyroiditis (HT) is considered to be mediated mainly by Th1 cells, but it is not known whether Graves’ disease (GD) is associated with Th1 or Th2 predominance. Th17 cells, a novel subset of Th cells, play a crucial role in the pathogenesis of various autoimmune disorders. In the present study, the expression of IL-17A and IFN-γ was investigated in patients with HT or GD. mRNA expression of IL-17A and IFN-γ in peripheral blood mononuclear cells (PBMC) from 43 patients with autoimmune thyroid disease (AITD) and in thyroid tissues from 40 AITD patients were measured by real-time qRT-PCR. The protein expression of IL-17A and IL-23p19 was examined by immunohistochemistry in thyroid tissues from 28 AITD patients. The mRNA levels of IL-17A and IFN-γ were higher in both PBMC and thyroid tissues of HT patients than in controls (mRNA levels are reported as the cytokine/β-actin ratio: IL-17 = 13.58- and 2.88-fold change and IFN-γ = 16.54- and 2.74-fold change, respectively, P < 0.05). Also, the mRNA levels of IL-17A and IFN-γ did not differ significantly in GD patients (P > 0.05). The high protein expression of IL-17A (IOD = 15.17 ± 4.8) and IL-23p19 (IOD = 16.84 ± 7.87) in HT was confirmed by immunohistochemistry (P < 0.05). The similar high levels of IL-17A and IFN-γ suggest a mixed response of Th17 and Th1 in HT, where both cells may play important roles in the destruction procedure by cell-mediated cytotoxicity.