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.

Two putative novel serotypes of Tibet orbivirus isolated from Culicoides spp.in Yunnan, China

Tibet orbivirus (TIBOV) was identified as a novel orbivirus in 2014. Antibodies against TIBOV were detected in cattle, Asian buffalo, and goats, while all the sequenced TIBOV strains were isolated from mosquitos and Culicoides. The known TIBOV strains have been classified into four putative serotypes. In this study, two TIBOV strains isolated from Culicoides spp. in Shizong County of Yunnan Province, China, were fully sequenced. The phylogenetic analysis of outer capsid protein 2 (VP2) indicated that these two viral strains belong to two novel putative serotypes of TIBOV. The updated putative serotypes may help in an investigation of the distribution and virulence of TIBOV.

Clinical features and prognostic influences of retropharyngeal lymph node metastasis in oropharyngeal and hypopharyngeal squamous cell carcinoma: a meta analysis / 中华耳鼻咽喉头颈外科杂志

Objective: To compare the clinical features and prognoses of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) with and without retropharyngeal lymph node metastases. Methods: PubMed, Cochrane, Web of Science, CNKI, VIP and Wanfang databases were searched for published literatures on retropharyngeal lymph node metastasis of oropharyngeal or hypopharyngeal squamous cell carcinoma (1900, 2021), and outcome indicators such as survival rate and related clinical features were extracted. The quality evaluation of the included literatures was carried out. RevMan 5.4 and Stata 16.0 software were used for data analysis. Results: A total of 18 literatures were included. Meta analysis showed that 3-year and 5-year survival rates and 5-year disease-specific survival rate of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma with retropharyngeal lymph node metastases were lower than those without metastases, 46.1% vs. 53.0%, 40.8% vs. 62.5% and 35.9% vs. 53.1%, respectively, and the differences were statistically significant (OR values were 0.26, 0.38, 0.38, and 95%CI were 0.10-0.69, 0.28-0.51, 0.23-0.65, respectively, all P values<0.05). There were statistically significant differences in clinical stage (III-IV), T stage (T3+T4), N stage (N2), positive cervical lymph node metastases and number of lymph node metastases (≥3) between the two groups (OR values were 4.28, 2.20, 2.88, 10.83, 6.53, and 95%CI were 1.70-10.74, 1.35-3.58, 1.90-4.34, 3.57-32.95, 1.75-24.38, respectively, all P<0.05). The sensitivity and specificity of preoperative imaging for diagnosing retropharyngeal lymph nodes metastases were respectively 0.72 (95%CI=0.54-0.85) and 0.98 (95%CI=0.74-1.00), and the area under curve (AUC) of summary receiver operating characteristic curve (SROC) was 0.84 (95%CI=0.80-0.87). Conclusions: The survival rate of patients with oropharyngeal or hypopharyngeal squamous cell carcinoma with retropharyngeal lymph node metastasis is significantly reduced, the clinical stage and T stage are late, and the cervical lymph node metastasis rate is high. Retropharyngeal lymph node metastasis is more insidious, the sensitivity of preoperative imaging diagnosis is not high.

Effects of comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome / 中华烧伤杂志

Objective: To investigate the characteristics and comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome. Methods: A retrospective observational study was conducted. From May 2012 to December 2021, the data of 19 patients with iatrogenic Cushing's syndrome discharged from the Department of Burns and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University were collected, including 8 males and 11 females, aged 28-71 (56±11) years, with 12 cases of infected acute wounds and 7 cases of infected chronic wounds. The lesions were located in the limbs, perianal, and sacrococcygeal regions, with original infection ranging from 9 cm×5 cm to 85 cm×45 cm. After admission, the patients were performed with multidisciplinary assisted diagnosis and treatment, and the wounds were treated with debridement and vacuum sealing drainage, according to the size, severity of infection, suture tension, and bone and tendon tissue exposure of wounds, direct suture or autologous skin and/or artificial dermis and/or autologous tissue flap transplantation was selected for wound repair. The levels of cortisol and adrenocorticotropic hormone (ACTH) of patients at 8:00, 16:00, and 24:00 within 24 h after admission were counted. After admission, the number of operations, wound repair methods, and wound and skin/flap donor site healing of patients were recorded. During follow-up, the wounds were observed for recurrent infection. Results: The cortisol levels of 16 patients at 8:00, 16:00, and 24:00 within 24 h after admission were (130±54), (80±16), and (109±39) nmol/L, respectively, and ACTH levels were (7.2±2.8), (4.1±1.8), and (6.0±3.0) pg/mL, respectively; and the other 3 patients had no such statistical results. After admission, the number of surgical operation for patients was 3.4±0.9. The following methods were used for wound repair, including direct suturing in 4 cases and autologous skin and/or artificial dermis grafting in 9 cases, of which 2 cases underwent stage Ⅱ autologous skin grafting after artificial dermis grafting in stage Ⅰ, and 6 cases had pedicled retrograde island flap+autologous skin grafting. The wound healing was observed, showing that all directly sutured wounds healed well; the wounds in 6 cases of autologous skin and/or artificial dermis grafting healed well, and the wounds in 3 cases also healed well after the secondary skin grafting; the flaps in 4 cases survived well with the wounds in 2 cases with distal perforators flap arteries circumfluence obstacle of posterior leg healed after stage Ⅱ debridement and autologous skin grafting. The healing status of skin/flap donor sites was followed showing that the donor sites of medium-thickness skin grafts in the thigh of 4 cases were well healed after transplanted with autologous split-thickness grafts from scalp; the donor sites of medium-thickness skin grafts in 3 cases did not undergo split-thickness skin grafting, of which 2 cases had poor healing but healed well after secondary skin grafting 2 weeks after surgery; the donor sites of split-thickness skin grafts in the head of 2 patients healed well; and all donor sites of flaps healed well after autologous skin grafting. During follow-up of more than half a year, 3 gout patients were hospitalized again for surgical treatment due to gout stone rupture, 4 patients were hospitalized again for surgical treatment due to infection, and no recurrent infection was found in the rest of patients. Conclusions: The infected wounds in patients with iatrogenic Cushing's syndrome have poor ability to regenerate and are prone to repeated infection. Local wound treatment together with multidisciplinary comprehensive treatment should be performed to control infection and close wounds in a timely manner, so as to maximize the benefits of patients.

Roles of Active Ingredients in Chinese Medicinals in Treatment of Acute Lung Injury by Regulating PI3K/Akt Signaling Pathway： A Review / 中国实验方剂学杂志

Acute lung injury is a common critical respiratory disease， which can further develop into acute respiratory distress syndrome （ARDS） with a high fatality rate， but there is no effective drug at present. Phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway is involved in cell proliferation， metabolism， survival， and motility through phosphorylation of numerous downstream effector molecules. It plays an important role in the development of acute lung injury by regulating mitochondrial function， apoptosis， autophagy， oxidative stress， and inflammatory response. The active ingredients in Chinese medicinals alleviate acute lung injury by targeting the PI3K/Akt signaling pathway. There has been an explosion of research on the treatment of acute lung injury by active ingredients in Chinese medicinals via PI3K/Akt signaling pathway， which is of great clinical research value. The article presented the first summary of studies exploring the correlation between PI3K/Akt signaling pathway and acute lung injury in recent years and summed up the protective effect of the active ingredients in Chinese medicinals against acute lung injury via PI3K/Akt signaling pathway， providing innovative mindsets and strategies for clinical application of active ingredients in Chinese medicinals in the treatment of acute lung injury.

The value of gadobenate dimeglumine multi-phase enhanced MRI in predicting the expression of cytokeratin19 in hepatocellular carcinoma / 中华放射学杂志

Objective:To investigate the predictive value of gadobenate dimeglumine (GD-BOPTA) multi-phase enhanced MRI for the expression of cytokeratin19 (CK19) in hepatocellular carcinoma (HCC).Methods:A total of 153 patients of HCC confirmed by pathology from June 2016 to February 2020 in First Affiliated Hospital of Fujian Medical University were enrolled retrospectively. According to the post-operative pathology, the patients were divided into CK19-negative group ( n=122) and CK19-positive group ( n=31). All the patients underwent MRI scan and Gd-BOPTA multi-phase enhanced scan before operation. MRI features on Gd-BOPTA MRI were compared between two groups. The qualitative indicators included tumor morphology, mosaic signs, intratumoral hemorrhage, intratumoral fat, non-rim arterial phase hyper-enhancement (APHE), non-peripheral washout, targetoid manifestation, enhanced capsule, corona enhancement, DWI signal, vascular invasion and hepatobiliary phase (HBP) enhancement. The quantitative indicator of tumor-to-liver signal ratio (SR) on HBP was recorded. The χ 2 test or Fisher exact probability method was used to compare the qualitative parameters between two groups, and student′s t test or Mann -Whitney U test was used for quantitative data. Predictive parameters were identified by univariate and multivariate logistic regression analysis to predict the value of the expression of CK19. The ROC curve was used to analyze the diagnostic efficacy of MRI parameters. Results:There were statistically significant differences between CK19-positive and CK19-negative groups ( P<0.05) in alpha fetoprotein, tumor morphology, non-rim APHE, non-peripheral washout, targetoid manifestation, corona enhancement, HBP enhancement and SR. Multivariate logistic regression analysis showed tumor morphology, corona enhancement, HBP enhancement and SR were independent predictors of CK19 expression in HCC. The area under the ROC curve of the combined four indicators for predicting CK19 expression in HCC was 0.823, and the sensitivity and specificity were 80.7% and 75.4%, respectively. Conclusions:Gd-BOPTA multi-phase enhanced MRI has an important value in the prediction of the expression of CK19 in HCC. The combination of signs of HBP can improve the prediction efficiency of CK19.

Association of Serum Glucocorticoids with Various Blood Pressure Indices in Patients with Dysglycemia and Hypertension: the Henan Rural Cohort Study / 生物医学与环境科学（英文）

Objective@#To our knowledge, no definitive conclusion has been reached regarding the relationship between glucocorticoids and hypertension. Here, we aimed to explore the characteristics of glucocorticoids in participants with dysglycemia and hypertension, and to analyze their association with blood pressure indicators.@*Methods@#The participants of this study were from the Henan Rural Cohort study. A total of 1,688 patients 18-79 years of age were included in the matched case control study after application of the inclusion and exclusion criteria. Statistical methods were used to analyze the association between glucocorticoids and various indices of blood pressure, through approaches such as logistic regression analysis, trend tests, linear regression, and restricted cubic regression.@*Results@#The study population consisted of 552 patients with dysglycemia and hypertension (32.7%). The patients with co-morbidities had higher levels of serum cortisol ( @*Conclusions@#Serum deoxycortisol was positively correlated with systolic blood pressure, pulse pressure, mean arterial pressure, mean blood pressure, and mean proportional arterial pressure. Glucocorticoids (deoxycortisol and cortisol) increase the risk of hypertension in people with dysglycemia, particularly in those with T2DM.

Prevention and control of HIV/AIDS in China: lessons from the past three decades / 中华医学杂志(英文版)

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

Quality Evaluation of Citri Sarcodactylis Fructus from Different Origins Based on HPLC Fingerprint and Chemometrics / 中国实验方剂学杂志

Objective:To establish the high performance liquid chromatography （HPLC） fingerprint of Citri Sarcodactylis Fructus， and to search for makers to characterize the quality difference of Citri Sarcodactylis Fructus from different origins coupled with chemometrics. Method:The analysis was performed on a Thermo Hypersil GOLD C₁₈ column （4.6 mm×250 mm， 5 μm） with mobile phase consisted of acetonitrile-0.05% phosphoric acid solution for gradient elution， and the detection wavelength was set at 254 nm. A total of 31 batches of samples were analyzed to establish the HPLC fingerprint of Citri Sarcodactylis Fructus. Similarity evaluation was performed by Traditional Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System （2012 edition） to confirm the common peaks， which were identified by comparison of reference substances. On the basis， chemometrics methods were used to analyze and evaluate the quality of Citri Sarcodactylis Fructus from different origins. At the same time， 3 batches of 5 species of decoction pieces from the genus <italic>Citrus</italic> in the family Rutaceae， including Citri Sarcodactylis Fructus， Aurantii Fructus Immaturus， Aurantii Fructus， Citri Reticulatae Pericarpium Viride and Citri Reticulatae Pericarpium， were randomly collected for evaluating the effectiveness and reliability of the established HPLC fingerprint of Citri Sarcodactylis Fructus. Result:HPLC fingerprint of Citri Sarcodactylis Fructus was established and 22 common peaks were identified. And seven common peaks among them were identified as 6，7-dimethoxycoumarin， diosmin， hesperidin， byakangelicin， 5，7-dimethoxycoumarin， bergapten and oxypeucedanin. Except for 2 batches of samples， the similarities of fingerprints between other 29 batches of samples were >0.9. The 31 batches of Citri Sarcodactylis Fructus were basically divided into 3 groups by cluster analysis and principal component analysis， which were consistent with the classification of three different producing areas. Eight differential markers were screened by orthogonal partial least squares discriminant analysis and four of them （5，7-dimethoxycoumarin， bergapten， 6，7-dimethoxycoumarin and diosmin） were identified by reference substances. Similarity evaluation of 5 species of decoction pieces from genus <italic>Citrus</italic> in the family Rutaceae was carried out by taking the reference fingerprint of Citri Sarcodactylis Fructus as treference chromatogram， similarity of Citri Sarcodactylis Fructus decoction pieces was 0.892-0.977， and the similarities of the other 4 kinds of decoction pieces were 0.215-0.517. Conclusion:The established fingerprint method is reasonable， effective and accurate for quality control of Citri Sarcodactylis Fructus， the characterization information is more comprehensive combined with chemometrics.

8-Azaguanine-induced autophagy contributes to its chemoresistance in hepatic cancer cells / 药学学报

Autophagy, an evolutionarily conserved process by which components of the cell are degraded in lysosomes, may facilitate survival of cancer cells under stress conditions. 8-Azaguanine (8-AG), an inhibitor of purine nucleotide biosynthesis, shows antineoplastic activity in multiple tumor cells. However, chemoresistance has restricted its development as an anticancer agent, and the mechanism of 8-AG resistance is not fully understood. We report here that 8-AG induces a protective autophagy to eliminate its cytotoxicity, and inhibition of autophagy increases cellular sensitivity of cancer cells to 8-AG treatment. Using HepG2 or SMMC-7721 hepatic cancer cell lines, we found that 8-AG inhibited cell viability and induced intrinsic apoptosis, accompanied by the up-regulation of the pro-apoptotic protein BimS, one of Bim (also known as BCL-2-like protein 11, BCL2L11) isoforms. Furthermore, 8-AG treatment enhanced the autophagy flux by promoting the dephosphorylation and activation of Unc-51-like autophagy activating kinase 1 (ULK1) via Akt/mTORC1 (mammalian target of rapamycin complex 1) signaling inhibition. Depletion of autophagy-related gene 7 (ATG7) markedly enhanced the level of BimS, and promoted cell death in response to 8-AG. 8-AG in combination with autophagy inhibitor chloroquine (CQ) or bafilomycin A1 (Baf A1) promoted the 8-AG-induced apoptosis in hepatic cancer cells. Altogether, these findings suggest that autophagy promotes chemoresistance of cancer cells for 8-AG, and blocking autophagy increases cellular sensitivity of cancer cells to 8-AG treatment.

An arthroscopic "inlay" Bristow procedure with suture button fixation: Surgical technique and radiology evaluation / 北京大学学报(医学版)

OBJECTIVE@#To introduce an arthroscopic "inlay" Bristow procedure based on the Mortise-Tenon joint structure concept using suture button fixation, and to evaluate its clinical and radiology results postoperatively with a minimal 3-year follow-up.@*METHODS@#A total of 56 patients who received arthroscopic "inlay" Bristow procedure with suture button fixation between June 2015 to June 2016 were eventually enrolled in this study. Radiological assessment on the 3D CT scan was performed preoperatively, immediately after operation, and postoperatively at the end of 3 months, 6 months and the final follow-up. Complications postoperatively were also recorded.@*RESULTS@#A total of 56 patients were finally included in this study. The mean follow-up time was (36.1±3.7) months. Coracoid grafts (middle point) were positioned at about 4 o'clock (123.8°±12.3°) in the En-face view. In the axial view, 95% (53/56) of the grafts positioning were measured as flush, 5% (3/56) as medial. Bone union rate was 96.4% at the final follow-up. At the end of 3 months, 6 months, and the final follow-up, the length of the coracoid graft was 96.9%±4.9%, 91.9%±6.2%, and 91.6%±6.6% of the immediate postoperative length, respectively. Compared with the immediate postoperative length, the length measured at the end of 3 months shortened not significantly (t=2.12, P > 0.05). The coracoid graft shortened more pronouncedly 6 months postoperatively (t=4.98, P < 0.05) and then remained almost constant over time (t=-0.75, P > 0.05), with all grafted coracoid graft retaining more than 90% of their initial length by the 3-year follow-up. And new bone formation at the junction between the coracoid graft and glenoid neck in the axial view were obviously noted in 25 cases. The quantitative evaluation showed that the glenoid area in En-face view was significantly increased at the final follow-up than that immediately after surgery [(9.72±1.22) cm2 vs. (9.42±1.11) cm2]. No degenerative changes were noted on CT images in all the patients at the final follow-up.@*CONCLUSION@#This study reported a series of "inlay" Bristow procedure with suture button fixation for recurrent shoulder dislocation, providing satisfactory union rate and excellent graft positioning. And using suture button fixation instead of screw can reduce osteolysis and complications related to hardware implantation. Moreover, the bone remodeling between the coracoid process and glenoid could be beneficial to restoring the anterior stability of shoulder joint in a long term follow-up.

Research progress in targeting homologous recombination repair for tumor therapy / 药学学报

Applying poly(ADP-ribose) polymerase inhibitors (PARPi) to the treatment of cancers with homologous recombination deficiency (HRDness) has been a great advance in the field of molecular therapeutics. However, in the clinic patients lacking the specific mutations or developing reverse mutations in the process of PARPi treatment may not benefit from PARPi monotherapy. Therefore, targeting homologous recombination (HR) repair with molecularly targeted agents is becoming an attractive research focus and is raising the concept of "chemical HRDness". HR repair is an evolutionarily conserved and extensively regulated process that employs sister chromatids as the template to repair DNA double-strand breaks with high fidelity. In addition to directly targeting HR components, modulation of regulatory pathways controlling HR repair is effective in achieving the "HRDness" phenotype; this includes modulation of the cell cycle checkpoint regulatory pathway, the phosphatidylinositol 3-kinase (PI3K) signaling pathway, the chromatin remodeling pathway, etc. Targeting HR repair can not only result in "synthetic lethality" when combined with PARPi, but also sensitizes cancers to traditional radio/chemotherapy and novel immunotherapy. In this review we describe the HR repair pathway and its regulatory pathways, summarize the preclinical and clinical outcomes of targeting HR repair, discuss the remaining problems in this field and provide a prospective on its application in tumor therapy.

Expression of CREB in children with recurrent wheezing and its effect on ORMDL3 gene expression / 中国当代儿科杂志

OBJECTIVE@#To study the expression level of cAMP response element-binding protein (CREB) in children with recurrent wheezing under three years of age and its effect on the expression of the serum orosomucoid 1-like protein 3 (ORMDL3) gene.@*METHODS@#Thirty-six children with recurrent wheezing under three years of age who visited the hospital from June 2017 to June 2019 were selected as the recurrent wheezing group. Twenty-four healthy children from physical examination were selected as the control group. The CREB expression level in peripheral blood was measured by quantitative real-time PCR. Human bronchial epithelial cells (BEAS-2B) were cultured, and dual-luciferase reporter assay and quantitative real-time PCR were used to investigate the effects of overexpression and siRNA interference of CREB on the promoter activity and mRNA expression of the ORMDL3 gene in the BEAS-2B cells.@*RESULTS@#The expression level of CREB in the recurrent wheezing group was significantly higher than that in the control group (P<0.001). In BEAS-2B cells, overexpression of CREB significantly up-regulated the promoter activity and mRNA expression of the ORMDL3 gene (P<0.05), while siRNA interference of CREB significantly reduced the promoter activity and mRNA expression of the ORMDL3 gene (P<0.05).@*CONCLUSIONS@#The expression of CREB is increased in children with recurrent wheezing, and CREB may be involved in the pathogenesis of recurrent wheezing by regulating expression of the ORMDL3 gene.

Analysis and Identification of Chemical Constituents of Citri Sarcodactylis Fructus by UPLC-Q-Orbitrap HRMS / 中国实验方剂学杂志

Objective::To analyze and identify the chemical constituents of Citri Sarcodactylis Fructus by an ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry (UPLC-Q-Orbirap HRMS) method. Method::Compounds were separated on Thermo Scientific Accucore™ C18 column (3 mm×100 mm, 2.6 μm). The mobile phase was 0.1% formic acid solution and 0.1% formic acetonitrile solution. The flow rate was 0.3 mL·min-1, and the column temperature was set at 30 ℃. HRMS was performed using an electrospray ion source (ESI), and scanned in a positive ion mode by means of full scan/data dependent secondary scan (Full MS/dd-MS2). Compound Discoverer 3.0 software that could be linked to mzCloud network database and local high-resolution mass spectrometry database of traditional Chinese medicine components was used to analyze the data, based on accurate molecular mass, retention behaviors and characteristic ion fragmentation of the compounds, as well as literature information and relevant reference materials. Result::Totally 54 chemical constituents in Citri Sarcodactylis Fructus were identified, including 16 flavonoids, 17 coumarins, 3 limonoids, 6 nucleosides and nucleobases, 2 organic acids, 3 aromatic aldehydes, 1 amino acid and 6 other components. Conclusion::The established UPLC-Q-Orbitrap HRMS method can be used to effectively and rapidly identify main chemical constituents of Citri Sarcodactylis Fructus. The findings provide a methodological reference and theoretical foundation for defining the pharmacodynamic material base and optimizing quality control index of Citri Sarcodactylis Fructus, which is of guiding significance for further development and utilization of the resources.

Disparity of human immunodeficiency virus incidence and drug resistance in college student, non-student youth and older men who have sex with men: a cross-sectional study from seven major cities of China / 中华医学杂志(英文版)

BACKGROUND@#Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM.@*METHODS@#We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤ 168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, <25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance.@*RESULTS@#Overall, 4,496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1,094 NSYM, and 2,837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100PY, 12.9 (95% CI: 9.8-16.1)/100PY, 6.8 (95% CI: 5.4-8.2)/100PY, and TDR prevalence were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age< 21-year-old, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (AOR: 2.5; 95% CI: 1.0-5.8).@*CONCLUSIONS@#College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.

Effects of berberine on learning and memory ability in vascular cognitive impairment rats / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of berberine on learning and memory ability in vascular cognitive impairment rats.@*METHODS@#Sixty-eight Wistar rats were randomly divided into control group (n=10), sham operated group (n=10) and the modeling group of vascular cognitive impairment rat (n=48), then the rats in modeling group were randomly divided into four groups (n=10): vehicle group, berberine low dose group (20 mg/kg), medium dose group (40 mg/kg) and high dose group (60 mg/kg). Bilateral common carotid arteries were occluded in rats to establish vascular cognitive impairment (VCI) model. Different doses of berberine were intraperitoneally injected into the treatment group and normal saline was intraperitoneally injected into the other groups once a day for a total of 34 days. After 28 days of administration, Morris water maze was used to test the learning and memory ability of rats. After the water maze experiment, the levels of superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha(TNF-α), interleukin-1 beta (IL-1β), 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) in the forebrain cortex were detected.@*RESULTS@#Compared to sham group, the escape latency in VCI group was significantly extended (P＜0.01) and the times of passing through the platform were decreased remarkably (P＜0.01). The levels of SOD, GSH and 5-HT in the hippocampus or anterior cortex were decreased significantly (P＜0.01), while the contents of MDA, TNF-α, IL-1β and MAO were increased remarkably (P＜0.01). Compared with VCI group, the escape latency in berberine-treated groups was shortened significantly (P＜0.01, P＜0.05) and the times of passing through the platform were increased remarkably (P＜0.01, P＜0.05), the levels of SOD, GSH and 5-HT were increased significantly (P＜0.01), while the contents of TNF-α, IL-1β and MAO were decreased remarkably (P＜0.01).@*CONCLUSION@#Berberine could significantly improve the spatial learning and memory abilities of rats with vascular cognitive impairment. The mechanism may be related to the effects of berberine on the hippocampal antioxidant stress, anti-inflammatory response and the monoamine neurotransmitter system in the forebrain cortex. Berberine 60 mg/kg dose group had better effect.

Regulatory Mechanism of Buyang Huanwu Tang on mTOR Protein that Mediates Autophagy in Mice with Pulmonary Fibrosis / 中国实验方剂学杂志

Objective:To observe the expression of mammalian target of rapamycin (mTOR) that mediates autophagy in pulmonary fibrosis and the effect of autophagy in the formation of pulmonary fibrosis, in order to explore the treatment mechanism of Buyang Huanwu Tang on pulmonary fibrosis. Method:Totally 144 C57BL/6 mice were randomly divided into 6 groups:sham operation group, model group, prednisone group, high-dose Buyang Huanwu Tang group, medium-dose Buyang Huanwu Tang group and low-dose Buyang Huanwu Tang group, with 24 mice in each group. The sham operation group was injected with the same amount of 0.9% saline. The remaining groups were treated with bleomycin tracheal injection to replicate the pulmonary fibrosis model. After modeling, sham operation group and model group were given 0.9% normal saline (0.01 g·kg-1·d-1), group high-dose Buyang Huanwu Tang group was given Buyang Huanwu Tang (28.08 g·kg-1·d-1), medium-dose Buyang Huanwu Tang group was given Buyang Huanwu Tang (14.04 g·kg-1·d-1), low-dose Buyang Huanwu Tang group was given Buyang Huanwu Tang(7.02 g·kg-1·d-1), and P group was given prednisone (0.455 g·kg-1·d-1) by gavage. The samples were taken in batches on the 7th, 14th and 28th days after modeling; degrees of alveolitis and fibrosis in mice were observed by hematoxylin-eosin (HE) staining and Masson staining. The mTOR protein, ribosomal S6 protein and microtubule associate protein 1 hight chain3-Ⅱ(MAP1LC3-Ⅱ) of mouse lung tissue were detected by Western blot; electron microscopy was used to observe the autophagy of lung tissue in mice. Result:Compared with the sham-operated group, the degrees of alveolitis and pulmonary fibrosis were significantly severer in the model group on 7th, 14th and 28th days (PPPPConclusion:The mTOR protein is activated in mice lung tissue, autophagy is inhibited, mTOR protein participates in the pathogenesis of pulmonary fibrosis by inhibiting autophagy; Buyang Huanwu Tang has a certain therapeutic effect on BLM-induced pulmonary fibrosis in mice, and its mechanism may be related to the down-regulation of mTOR protein expression that mediates autophagy.

Survival Analysis of 148 Patients with Primary Diffuse Large B Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical outcome of the patients with primary diffuse large B-cell lymphoma（DLBCL）.@*METHODS@#Clinical data of 148 patients with DLBCL in our hospital and cancer hospital from March 2006 to April 2016 were retrospectively analyzed. Kaplan-Meier analysis was used to estimate progression-free survival（PFS）and overall survival（OS）.@*RESULTS@#5-year OS and PFS rates were 85% and 69%，respectively. The survival analysis showed that 5-year OS rate of R-CHOP group was significantly higher than that of CHOP alone group（89% vs. 70%，P60 years），poor ECOG score（≥2），advanced stage（Ⅲ-Ⅳ），higher IPI score（≥3），CHOP alone and absence of radiotherapy related with poor survival rate. Furthermore，multivariate analysis showed that age>60 year significantly related with the worse OS.@*CONCLUSION@#Age >60 year is an important independent prognostic factor to predict worse OS or PFS.

Photosynthetic characteristics and active ingredients differences of Asarum heterotropoides var. mandshuricum under different light irradiance / 中国中药杂志

Chlorophyll content,leaf mass to per area,net photosynthetic rate and bioactive ingredients of Asarum heterotropoides var. mandshuricum,a skiophyte grown in four levels of solar irradiance were measured and analyzed in order to investigate the response of photosynthetic capability to light irradiance and other environmental factors. It suggested that the leaf mass to per area of plant was greatest value of four kinds of light irradiance and decreasing intensity of solar irradiance resulted in the decrease of leaf mass to per area at every phenological stage. At expanding leaf stage,the rate of Chla and Chlb was 3. 11 when A. heterotropoides var. mandshuricum grew in full light irradiance which is similar to the rate of heliophytes,however,the rate of Chla and Chlb was below to 3. 0 when they grew in shading environment. The content of Chla,Chlb and Chl( a+b) was the greatest value of four kinds of light irradiance and decreasing intensity of solar irradiance resulted in its decreasing remarkably( P<0. 05). The rate of Chla and Chlb decreased but the content of Chla,Chlb and Chl( a+b) increased gradually with continued shading. The maximum value of photosynthetically active radiation appeared at 10: 00-12: 00 am in a day. The maximum value of net photosynthetic rate appeared at 8: 30-9: 00 am and the minimum value appeared at 14: 00-14: 30 pm at each phenological stage if plants grew in full sunlight. However,when plants grew in shading,the maximum value of net photosynthetic rate appeared at about 10: 30 am and the minimum value appeared at 12: 20-12: 50 pm at each phenological stage. At expanding leaf stage and flowering stage,the average of net photosynthetic rate of leaves in full sunlight was remarkably higher than those in shading and it decreased greatly with decreasing of irradiance gradually( P < 0. 05). However,at fruiting stage,the average of net photosynthetic rate of leaves in full sunlight was lower than those in 50% and 28% full sunlight but higher than those in 12% full sunlight. All photosynthetic diurnal variation parameters of plants measured in four kinds of different irradiance at three stages were used in correlation analysis. The results suggested that no significant correlation was observed between net photosynthetic rate and photosynthetically active radiation,and significant negative correlation was observed between net photosynthetic rate and environmental temperature as well as vapor pressure deficit expect for 12% full sunlight. Positive correlation was observed between net photosynthestic rate and relative humidity expect for 12% full sunlight. Significant positive correlation was observed between net photosynthetic rate and stomatal conductance in the four light treatments. Only,in 12% full sunlight,the net photosynthetic rate was significantly related to photosynthetically active radiation rather than related to environmental temperature,vapor pressure deficit and relative humidity. In each light treatment,a significant positive correlation was observed between environmental temperature and vapor pressure deficit,relative humidity as well as stomatal conductance. Volatile oil content was 1. 46%,2. 16%,1. 56%,1. 30% respectively. ethanol extracts was 23. 44%,22. 45%,22. 18%,21. 12% respectively. Asarinin content was 0. 281%,0. 291%,0. 279% and 0. 252% respectively. The characteristic components of Asarum volatile oil of plant in different light treatments did not change significantly among different groups.

Effects of Triptolide Combined with Homoharringtonine on Proliferation and Apoptosis of KG-1α Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect and possible mechanism of low concentration of triptolide (TPL) combined with homoharringtonine (HHT) on the proliferation and apoptosis of KG-1α cells.</p><p><b>METHODS</b>CCK-8 method was used to detect the antiproliferating effects of different concentrations of TPL and HHT single-use and combined use on KG-1α cells, and the combined index (CI) was calculated. The colony formation ability was also determined by methylcellulose colony formation assay, cell surface molecules, apoptosis rate and cell cycle changes were detected by flow cytometry. Westerrn blot was used to detect the expression of Akt signaling pathway related proteins before and after low dose TPL combined with HHT using.</p><p><b>RESULTS</b>High expression of CD34 and CD123 were on KG-1a cells, which being lack expression of CD38. TPL and HHT dose-dependently inhibited the proliferation of KG-1α cells. Compared with low dosage TPL and HHT single-use groups, the cell proliferation and colony formation efficiency were lower, and the cell apoptosis rate was higher in the combined group. CI values also indicated that low concentration TPL combined with HHT possessed highly synergistic effect. After the combination of the 2 drugs, the expressions of P-Akt, P-Akt, BCL-2, PARP and survivin protein were down-regulated and the cleavage of PARP protein was increased.</p><p><b>CONCLUSION</b>Low concentration of TPL combined with HHT can synergistically inhibit KG-1α cell proliferation and induce its apoptosis through the PI3K/Akt signaling pathway and downstream protein.</p>