Potent inhibition of human and rat 17ß-hydroxysteroid dehydrogenase 1 by curcuminoids and the metabolites: 3D QSAR and in silico docking analysis.

Curcumin, an extensively utilized natural pigment in the food industry, has attracted considerable attention due to its potential therapeutic effects, such as anti-tumorigenic and anti-inflammatory activities. The enzyme 17ß-Hydroxysteroid dehydrogenase 1 (17ß-HSD1) holds a crucial position in oestradiol production and exhibits significant involvement in oestrogen-responsive breast cancers and endometriosis. This study investigated the inhibitory effects of curcuminoids, metabolites, and analogues on 17ß-HSD1, a key enzyme in oestradiol synthesis. Screening 10 compounds, including demethoxycurcumin (IC50, 3.97 µM) and dihydrocurcumin (IC50, 5.84 µM), against human and rat 17ß-HSD1 revealed varying inhibitory potencies. These compounds suppressed oestradiol secretion in human BeWo cells at ≥ 5-10 µM. 3D-Quantitative structure-activity relationship (3D-QSAR) and molecular docking analyses elucidated the interaction mechanisms. Docking studies and Gromacs simulations suggested competitive or mixed binding to the steroid or NADPH/steroid binding sites of 17ß-HSD1. Predictive 3D-QSAR models highlighted the importance of hydrophobic regions and hydrogen bonding in inhibiting 17ß-HSD1 activity. In conclusion, this study provides valuable insights into the inhibitory effects and mode of action of curcuminoids, metabolites, and analogues on 17ß-HSD1, which may have implications in the field of hormone-related disorders.

[The influencing factors on the spinal sagittal alignment and global balance status of degenerative thoracolumbar kyphosis].

Objective: To explore the effect of degenerative thoracolumbar kyphosis (DTLK) on the sagittal alignment of the spine, as well as the impact on spinal parameters and imbalance secondary to thoracolumbar kyphosis. Methods: A case-control study. A total of 128 DTLK patients who aged over 50 years [thoracolumbar kyphosis (TLK)>15°] treated in Peking University People's Hospital from January 2018 to December 2021 (DTLK group) were retrospectively included in this study. Other 73 contemporaneous patients with lumbar spinal stenosis or disc herniation without thoracolumbar kyphosis (TLK=0°±15°) were enrolled into the control group. The following parameters were obtained on spine X-ray: TLK, thoracic kyphosis (TK), lumbar lordosis (LL) and sagittal vertical axis (SVA). In addition, the osteoporosis (OP) was evaluated by dual-emission X-ray absorptiometry (DXA), and the L5/S1 disc signal grading (Pfirrmann grading) was evaluated on MRI. Based on the age, the Lafage formula SVA=2× (age-55)+25 was used to distinguish balance/imbalance, and the DTLK patients were divided into balanced and an imbalanced group, the characteristics and influencing factors of the loss of sagittal balance in this population were clarified, and the interaction among various parts of the spine under a state of balance was analyzed too. Results: The TK (30.0°±13.5° vs 24.2°±7.4°) and TLK (26.6°±9.7° vs 6.0°±6.6°) in the DTLK group were both larger than those in control group while LL was smaller (34.4°±17.7° vs 44.2°±10.3°) (all P<0.001). TK was correlated to TLK (r=0.234, P=0.008) and LL (r=0.539, P<0.001) in DTLK group. LL loss was positively correlated to L5/S1 disc signal reduction (r=0.253, P=0.044). LL loss [RR=1.04(1.01-1.08)] and OP [RR=3.97(1.09, 14.50)] were influencing factors for the occurrence of imbalance in DTLK patients. The influencing factors for TK in DTLK balance group were LL (ß=0.572, P<0.001) and age (ß=0.351, P=0.045). The positive influencing factor for TK in imbalanced group is LL (ß=0.209, P=0.015), and the impact is weaker than balanced group. Conclusions: Loss of LL and osteoporosis are more likely to cause imbalance and kyphosis in DTLK patients. In DTLK balance group, the proximal spine is regulated by lumbar spine, and the synergistic effect between the two parts maintains balance.

[Effects of periodontitis on bone and tryptophan metabolism of gut microbiota in estrogen-deficient mice].

Objective: To study the effects of periodontitis on bone and tryptophan metabolism of gut microbiota in the context of estrogen deficiency. Methods: Thirty-two female C57BL6/J mice were randomly divided into four groups based on table of random numbers (n=8 in each group): Sham group, in which mice were given sham surgery; Sham_Lig group, in which mice were given sham surgery and were induced to periodontitis by ligating the bilateral maxillary second molars with 5-0 silk threads at the fourth week; Ovx group, in which mice were given bilateral ovariectomy; Ovx_Lig group, in which mice were given bilateral ovariectomy and were induced to periodontitis at the fourth week. After 8 weeks of ligation, the mice of 4 groups were euthanized for collecting the samples of femur, tibia, mandible and skull. Those samples were scanned by micro-CT to measure the bone mineral density (BMD), bone volume versus total volume ratio (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular spacing (Tb.Sp). The cecum contents of 4 groups of mice were collected for gut microbiota 16S rRNA gene sequencing. The tryptophan and its metabolites in intestinal tracts were detected by liquid chromatography-mass spectrometry. Pearson correlation analysis was performed to analyze the correlation between the abundance of gut microbiota and the content of tryptophan and its metabolites. Results: Femur BMD [(82.23±3.97) mg/cm3], BV/TV [(9.25±1.37)%] and Tb.Th [(70.95±5.70) µm] in Ovx_Lig group were significantly lower than Ovx group [(96.30±3.76) mg/cm3 (P=0.004); (14.45±1.55)% (P=0.022) and (87.58±8.02) µm (P<0.001), respectively]. The ß-diversity analysis of gut microbiota based on Bray-Curtis distance showed that samples of Ovx_Lig group and Ovx group were obviously grouped. Linear discriminant analysis effect size (LEfSe) showed that Alistipes was the representative genus in Ovx_Lig group. The relative abundance of Alistipes in Ovx_Lig group [(0.42±0.14)%] were significantly higher than that in Ovx group [(0.17±0.05)%] (t=4.45, P<0.001). Tryptophan metabolism analysis showed that the content of kynurenic acid [(531.12±158.60) ng/g] in Ovx_Lig group were significantly higher than that in Ovx group [(400.42±57.96) ng/g] (t=2.19, P=0.046). And the content of indole-3-carbaldehyde [(383.37±144.06) ng/g] in Ovx_Lig group were significantly lower than Ovx group [(701.72±141.93) ng/g] (t=4.45, P<0.001). Correlation analysis showed that relative abundance of Alistipes was positively correlated with kynurenic acid (r=0.32, P=0.088), while negatively correlated with indole-3-carbaldehyde (r=-0.32, P=0.088). Conclusions: Periodontitis can induce bone destruction of femur in estrogen-deficient mice, the mechanism of which may be related to Alistipes in gut and the tryptophan metabolites kynurenic acid and indole-3-carbaldehyde.

Lacticaseibacillus rhamnosus GG Improves Periodontal Bone Repair via Gut-Blood Axis in Hyperlipidemia.

Periodontal bone regeneration remains a clinical challenge, and hyperlipidemia can aggravate alveolar bone resorption. Probiotics have recently been reported to improve bone mass. We aimed to determine the role of Lacticaseibacillus rhamnosus GG (LGG) in periodontal bone regeneration improvement within the context of periodontitis with hyperlipidemia. A Sprague Dawley rat model for periodontitis, hyperlipidemia, and periodontal fenestration defect was constructed (n = 36) and administered LGG gavage for 6 wk (the rats were subsequently sacrificed). Fecal microbiota from donor rats 3 wk after LGG gavage was transplanted into recipient rats to evaluate the role of LGG-modulated gut microbiota in periodontal bone regeneration. Regenerated bone mass was detected using micro-computerized tomography and hematoxylin and eosin stain. Gut microbiota was analyzed using 16S ribosomal RNA sequencing. Serum metabolites were detected by liquid chromatography-mass spectrometry (6 wk after LGG gavage). The pro-osteogenic effects of screened serum metabolite were verified in vitro on bone marrow mesenchymal stem cells (BMMSCs). We found that the bone mineral density, bone volume (BV), trabecular bone volume fraction (BV/TV), and trabecular thickness of the regenerated periodontal bone increased after LGG gavage (P < 0.05) but had little effect on oral flora. After LGG gavage, Staphylococcus, Corynebacterium, and Collinsella in the gut of donors were significantly changed, and these differences were maintained in recipients, who also showed increased trabecular thickness of the regenerated periodontal bone (P < 0.05). These key genera were correlated with BV/TV and BV (P < 0.05). In addition, LGG gavage significantly regulated bone-related blood metabolites, of which selenomethionine promoted BMMSC osteogenesis. Notably, selenomethionine was associated with key gut genera (P < 0.05). Collectively, LGG improved periodontal bone regeneration in the context of periodontitis with hyperlipidemia by modulating gut microbiota and increasing pro-osteogenic metabolites in the blood. These results reveal new insights into the use of probiotics to promote periodontal bone regeneration via the gut-blood-bone axis.

[Expert consensus on the management of adverse events of CDK4/6 inhibitors in breast cancer].

Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors are anti-tumor agents for the treatment of hormone receptor-positive breast cancer. Palbociclib, abemaciclib and dalpiciclib have been approved for the treatment of breast cancer in China. Common adverse effects of CDK4/6 inhibitors include bone marrow suppression, gastrointestinal toxicities, liver dysfunction, and skin or subcutaneous tissue adverse reactions (AEs). The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence, clinical manifestations, and grading of the AEs. This expert consensus reports measures of AE management on the basis of experience of clinical practice and the latest advances worldwide, aiming to guide clinical practice by the way of managing AE and help to choose the best treatment regimen.

[Analysis on the HIV-1 molecular transmission characteristics of newly confirmed HIV/AIDS in Jiaxing city, 2017-2018].

Objective: To analyze the relationship between infection and transmission of HIV/AIDS, explore the characteristics of the HIV-1 transmission network, and provide evidence for formulating targeted prevention and control measures. Methods: The newly confirmed HIV/AIDS in Jiaxing from 2017 to 2018 were selected for the study. The sociodemographic and infection transmission-related information was gathered. The blood samples were collected and RNA was extracted, RT-PCR and nested PCR amplified the pol gene of HIV-1. The phylogenetic tree was constructed by Mega 6.0 software for subtype analysis. The genetic distance between strains was calculated, and the molecular transmission network was drawn by using Cytoscape 3.6.0 software. The results of the epidemiological study based on the molecular transmission network were analyzed. Results: There were fifteen HIV-1 gene subtypes in 517 cases of HIV/AIDS. The main subtypes were CRF01_AE (37.1%)、CRF07_BC (36.2%) and CRF08_BC (11.8%). Under the 1.0% gene distance threshold, 87 molecular clusters were established, and the total clustering rate was 45.8% (237/517). The cluster risk factors were 60-81 age group (compared with 14-24 age group, OR=2.690, 95%CI:1.058-6.844), married (compared with unmarried, OR=1.698, 95%CI:1.003-2.875), CRF07_BC subtype (compared with CRF01_AE, OR=2.203, 95%CI:1.426-3.404). The largest molecular cluster, CRF07_BC-1, consisted of 50 cases (including 21 cases confirmed in 2017 cases and 29 confirmed in 2018). Multivariate analysis showed that characteristics of unmarried (compared with married, OR=2.482, 95%CI:1.140-5.402), gays (compared with heterosexual, OR=3.163, 95%CI:1.543-6.483), cases with high-risk transmission (compared with other cases, OR=7.631, 95%CI:1.783-32.654), confirmed in Nanhu and Pinghu districts of Jiaxing (compared with other districts, OR=2.225, 95%CI:1.074-4.608) were risks for entering the largest molecular cluster. There were seven suspected high-risk transmission MSM in the largest molecular cluster. The first debut of homosexual behavior was from 2010 to 2018, and the median number of gay partners was 20 (P25, P75：10, 100) within two years before being diagnosed. Six reported a recent history of looking for gay partners in an MSM dating place in Nanhu district. Conclusions: The HIV-1 subtypes of newly confirmed HIV/AIDS were diverse, mainly sporadic in Jiaxing from 2017 to 2018. There were geographical aggregation characteristics and suspected some high-risk transmission cases, suggesting that rapid transmission and targeted intensive intervention are needed.

[Comparable study of alternative-level and all-level Arch mini-plate fixation for unilateral open-door laminoplasty].

Objectives: To compare the clinical effect of alternative-level and all-level Arch mini-plate fixation in patients undergoing unilateral open-door laminoplasty. Methods: Clinical data of 134 patients administrated in the Peking University International Hospital for multistage cervical spondylotic myelopathy from March 2015 to March 2019 were reviewed retrospectively. There were 63 males and 71 females with an average age of (62±8) years and a mean disease course of (18±7) months (3-37 months). All the patients underwent posterior cervical unilateral open-door laminoplasty with Arch titanium plate fixation. All the patients were divided into two groups according to the different amount of titanium plates used during operation as follow: group A, Arch plates were fixed at the door sides of C3, C5 and C7 (n=68) and group B, Arch plates were fixed at the door sides of C3, C4, C5, C6 and C7 (n=66). Operation time, intraoperative blood loss, postoperative hospitalization days and the cost of consumables, the Japanese orthopaedic association (JOA) score, cervical dysfunction index (NDI), the rates of improved JOA score, cervical curvature index, C2-7 Cobb angle, cervical range of motion, sagittal diameter of vertebral canal, opening angle of laminar, hinges bone healing and surgery related complications (axial symptoms, C5 nerve root palsy, screw loosening, laminar re-closing, cervical kyphosis, etc.) were recorded and compared between the two groups. Results: There was no complications during the operation, and the mean follow-up was (20±8) months (14-48 months). There was no statistically significant difference between the two groups in terms of gender, age, course of disease and compression segments (all P>0.05). There was no statistically significant differences between the two groups in operation time, intraoperative blood loss and postoperative hospital stay too (all P>0.05). The cost of consumables in group A was (34 970±1 325) yuan, and it was (57 450±2 161) yuan in group B, the difference between the two groups was statistically significant (P<0.01). The JOA and NDI score were significantly improved 3 months and 1 year after operation in both groups (both P<0.05). The sagittal diameter of each segment of the spinal canal at C3, C4, C5, C6 and C7 were all significantly increased in both groups 3 months and 1 year after surgery (all P<0.05). The C2-7 Cobb angle and cervical curvature index were all significantly reduced in both groups 3 months and 1 year after surgery (all P<0.05). The cervical range of motion in both groups was significantly reduced 3 months and 1 year after surgery compared with that before surgery (both P<0.05). The range of motion of the cervical spine in group A was significantly higher than that in group B (P<0.05). The opening angles of C4 and C6 segment lamina in group A 3 months and 1 year after operation were significantly lower than those in group B (all P<0.05). At 3 months after the operation, the hinges healing rate of C4 and C6 in group B was significantly better than that of group A (both P<0.05). At 1 year after the operation, there was no difference in the hinges healing rate of C4 and C6 in the two groups (both P>0.05). There was no statistically significant difference in postoperative complications between the two groups (P>0.05). Conclusions: The safety and early clinical efficacy of alternative-level and all-level Arch titanium plate fixation in posterior cervical unilateral open-door laminoplasty are comparable, alternative-level fixation can effectively reduce the cost of hospitalization. The open Angle loss and lower early hinges healing rate of the non-fixed segment in the alternative-level fixed group does not lead to laminar re-closing in early period of post operation.

[Clinicopathological features of polymorphous low-grade neuroepithelial tumor of the young].

Objective: To investigate the clinicopathological features, diagnosis and prognosis of polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Methods: Two cases of PLNTY diagnosed during January 2016 to December 2019 were collected from Ningbo Diagnostic Pathology Center, Zhejiang, China. The clinical features, histopathological characteristics, immunohistochemical and molecular genetic findings were analyzed and the relevant literature was reviewed. Results: The two patients were both female, at the ages of 14 and 25 years, respectively. Both patients presented with seizure attacks. The imaging study showed a mixed signal in the cerebral cortex, located in the occipital and temporal lobes, respectively. Microscopically, the tumors were characterized by the invariable presence of oligodendroglioma-like appearance, often with calcification. Immunohistochemically, the tumors were diffusely and intensely CD34 positive with ramified, CD34-expressing neural elements in regional cortex. The tumors were positive for GFAP, Olig2 and ATRX, and negative for IDH1, Neu N, nestin and EMA. The Ki-67 labeling index was less than 2%. The case number 2 harbored the BRAF V600E mutation, while the case number 1 was negative for both the BRAF V600E mutation and 1p/19q codeletion. Both patients recovered very well and were free of seizures after the following-up of 2 and 24 months, respectively. Conclusions: PLNTY is an uncommon neuroepithelial tumor. Histopathologic and immunohistochemical examinations are necessary for establishing the diagnosis and for excluding oligodendroglioma. PLNTY should be considered as a benign tumor corresponding to WHO Grade I. The prognosis is overall good after complete tumor-resection.

[Expert consensus on the management of adverse events of ErbB family tyrosine kinase inhibitors in breast cancer].

Human epidermal growth factor receptor-2 (HER-2) tyrosine kinase inhibitors (TKI) is the targeted drug of HER-2-positive breast cancer. Lapatinib, pyrotinib and neratinib, as ErbB family TKIs, have been approved by National Medical Products Administration and applied in the treatment of HER-2 positive breast cancer in China. The most common adverse effects (AEs) of TKI agents include diarrhea, drug-induced liver injury (DILI), nausea, vomiting, skin toxicity, cardiotoxicity and oral mucositis. The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence and characteristics of AEs of TKI, evaluated the manifestations and severity of AEs, and formulated the consensus of the management of common AEs based on the clinical experiences and updated advances from domestic and abroad studies. This consensus aims to provide the practical strategy for clinicians in the management of ErbB-family TKI-related AEs in China, and eventually enhance the patients' compliance and improve the therapeutic efficacy.

[Comparison of percutaneous pedicle screw placement under O-arm navigation with traditional percutaneous pedicle screw placement in patients with thoracolumbar fractures without neurological symptoms].

Objective: To investigate the accuracy and clinical efficacy of percutaneous pedicle screw placement under O-arm navigation and traditional fluoroscopy in patients with thoracolumbar fractures without neurological symptoms. Methods: From July 2016 to July 2018, 72 patients with thoracolumbar fractures in Peking University International Hospital without neurological symptoms were divided into two groups, group A and group B. In group A, 36 patients underwent the surgery of percutaneous pedicle screw implantation under traditional fluoroscopy and 168 pedicle screws were inserted. In group B, 36 patients underwent the surgery of percutaneous pedicle screw implantation under O-arm guided fluoroscopy and 164 pedicle screws were inserted by the same surgeon. The general condition, operation condition, radiation dose, fluoroscopy time of single screw, screw placement time and accuracy, visual analogue score (VAS) score, Oswestry dysfunction index (ODI), kyphosis Cobb's angle, anterior edge height of 1 week and 6 months after surgery were compared. The data were compared with paired t test between the two groups. Results: There was no significant differences between the two groups in general condition, intraoperative blood loss, length of hospital stay, VAS, ODI, kyphosis Cobb's angle, and anterior edge height of the injured vertebra (all P>0.05). The operation time was (99±14) min in group A and (75±10) min in group B, the average screw setting time was (15.8±2.6) min in group A and (11.8±3.3) min in group B, the fluoroscopy time of each screw was (38.0±2.0) s in group A and (28.5±2.8) s in group B, the radiation dose of each surgery was (563±163) cGy/cm(2) in group A and (378±70) cGy/cm(2) in group B; the above-mentioned data of group A were all superior to those in group B and the differences between the two groups were all statistically significant (t=8.48, 5.73, 16.30, 6.25, all P<0.05). Rampersaud grading in group A was better than group B, and the differences between the two groups was statistically significant(χ(2)=12.2, P<0.05). Conclusion: The O-arm navigation system could not only provide high-definition navigation images and achieve high-precision navigation operations, which is more accurate than traditional pedicle screws placement, but also contribute to the reconstruction of spinal stability and reduce radiation dose, pedicle screws placement and operating time.

MiR-224-5p targets EGR2 to promote the development of papillary thyroid carcinoma.

OBJECTIVE: Various microRNAs (miRNAs) have been reported to be involved in the pathogenesis and development of human cancers, including papillary thyroid carcinoma (PTC). However, the role of miR-224-5p in PTC progression remains unclear. Therefore, the purpose of this study is to illuminate the function of miR-224-5p in PTC. PATIENTS AND METHODS: Expression of miR-224-5p and EGR2 was examined in PTC by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Transwell assay was used to detect cell migration and invasion. Western blot analysis was used to detect epithelial-mesenchymal transition (EMT). The relationship between miR-224-5p and EGR2 was confirmed by Dual-Luciferase assay. RESULTS: Upregulation of miR-224-5p and downregulation of EGR2 expression were detected in PTC tissues and cells. Upregulation of miR-224-5p was found to be associated with TNM stage and lymph node metastasis. Meanwhile, it also predicted poor prognosis in PTC patients. Functionally, upregulation of miR-224-5p promoted cell metastasis and EMT in PTC. In addition, miR-224-5p was detected to directly target EGR2. EGR2 expression was negatively correlated with EGR2 expression in PTC. Of note, overexpression of EGR2 attenuated the carcinogenic effects of miR-224-5p in PTC. CONCLUSIONS: MiR-224-5p promotes cell migration, invasion, and EMT in PTC by targeting EGR2.

[Etiological diagnosis and clinical evaluation of isolated fetal ascites].

Objective: To explore the correlation between prenatal clinical data with etiological diagnosis and neonatal outcome in isolated fetal ascites. Methods: Totally, 36 pregnancy cases diagnosed as isolated fetal ascites by ultrasound in Provincial Hospital Affiliated to Shandong University from June 22nd, 2016 to September 28th, 2018 were collected. Invasive prenatal diagnosis was performed by taking fetal cord blood, amniotic fluid, and fetal ascites respectively for cytogenetics, molecular genetics and biochemical examination and the impact of intrauterine therapeutic procedures on neonatal outcomes was evaluated as well. The correlation among prenatal examination, pathogeny and prognosis was analyzed by Fisher's exact test. Results: (1) The prognosis of isolated fetal ascites initially presenting ≥28 weeks was better than that before 28 weeks, survival rate of 1-year-old were 13/15 and 9/17,respectively, the difference was statistically significant (P<0.05). (2) The etiologic diagnosis rate of ascites before delivery was 31%(11/36), which increased to 53%(19/36) totally after birth. Characteristics of cases which were defined prenatally were as follows: 8 cases of digestive tract diseases showed ultrasonic abnormalities, including echogenic bowel, bowel dilatation and polyhydramnios; platelet level in umbilical cord blood of fetuses infected with cytomegalovirus were below 100 × 10(9)/L in 2 cases; 1 case of urinary system malformation showed megalocystis and hydronephrosis. Cases which were defined causes after birth included: 3 fetuses with chyloperitonium presented persistent fetal ascites; 3 cases of digestive-related causes were rectal duplication with infection, mesentery stenosis, and intestinal atresia; other causes included Pierre-Robin syndrome and Budd-Chiari syndrome. (3) The live birth rate was 72% (26/36) and survival rate of 1-year-old was 61% (22/36). And 9/10 of infants who underwent surgeries got good outcomes. Fetal ascites due to abdominal or pelvic factors turned well in 13/16 of cases. Conclusions: The pregnancy outcome of fetal isolated ascites depends mainly on primary causes. Gastrointestinal abnormality is one of the most common causes. Excluded intrauterine infection, chromosomal abnormality and abnormal systemic ultrasonic findings, fetus with reduced ascites as the pregnancy progresses will get good outcome.

Epigenetic modulations and lineage plasticity in advanced prostate cancer.

Prostate cancer is the most common cancer and second leading cause of cancer-related death in American men. Antiandrogen therapies are part of the standard of therapeutic regimen for advanced or metastatic prostate cancers; however, patients who receive these treatments are more likely to develop castration-resistant prostate cancer (CRPC) or neuroendocrine prostate cancer (NEPC). In the development of CRPC or NEPC, numerous genetic signaling pathways have been under preclinical investigations and in clinical trials. Accumulated evidence shows that DNA methylation, chromatin integrity, and accessibility for transcriptional regulation still play key roles in prostate cancer initiation and progression. Better understanding of how epigenetic change regulates the progression of prostate cancer and the interaction between epigenetic and genetic modulators driving NEPC may help develop a better risk stratification and more effective treatment regimens for prostate cancer patients.

[The expression of VHL/HIF signaling pathway in the erythroid progenitor cells with chronic mountain sickness].

Objective: To investigate the expression and interaction of VHL/HIF-α pathways including HIF-1α, HIF-2α as well as VHL in erythroid progenitor cells of bone marrow from chronic mountain sickness (CMS) patients. Methods: A total of 25 patients with CMS and 21 healthy controls were recruited for this study. The CD71(+)CD235a(+) cells in bone marrow mononuclear cells, marked as erythroid progenitor cells, were isolated using MACS separation technology. The expression levels of HIF-1α, HIF-2α and VHL in erythroid progenitor cells were detected by Western blotting and real-time fluorescence quantitative PCR. Results: The mRNA levels of HIF-2α were higher in erythroid progenitor cells of CMS than in healthy controls [1.68 (0.81, 2.22) vs 0.98 (0.60, 1.19), P<0.05], while HIF-1α and VHL mRNA levels were similar between the two groups (P>0.05). Spearman analyses indicated that HIF-2α mRNA was positively associated with hemoglobin (Hb) levels in the erythroid progenitor cells of CMS (ρ=0.504, P<0.05). Furthermore, the mRNA level of HIF-2α was correlated with the mRNA level of VHL in the erythroid progenitor cells of CMS (ρ=0.647, P<0.05).The protein levels of HIF-2α in the erythroid progenitor cells of CMS were higher than that of healthy controls [0.94(0.68, 3.30) vs 0.59(0.30, 0.88), P<0.05], but the protein levels of HIF-1α and VHL were similar between the two groups (P>0.05). Conclusions: The abnormal increased expression of HIF-2α in the erythroid progenitor cells of CMS patients leads to the abnormal expression of hypoxia sensitive genes downstream, participating in the occurrence and development of CMS.

Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.

Co-receptor tropism has been identified to correlate with HIV-1 transmission and the disease progression in patients. A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1. In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%. Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85). No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus. The co-receptor tropism appeared to be associated with the virus genotype; a significantly more CXCR4-use was predicted in CRF01_AE infections whereas all CRF07_BC and CRF08_BC were predicted to use CCR5 co-receptor. Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P < 0.05). The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses. Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B. These findings may offer important implications for clinical practice and enhance our understanding of HIV-1 biology.

[Preliminary study of auditory cortex resting-state fMRI features for adult post-lingual deafness].

Objective: To understand the auditory cortex resting-state fMRI features for adult post-lingual deafness.Method: The author performed functional connectivity analysis on the study subjects with resting-state fMRI,the region of interest(ROI) of which were based separately on the left and right sides of primary auditory cortex. The data were collected from 8 cases with severe or above sensorineurally post-lingual deafness,compared to a control group of 8 cases with normal hearing. Result: When ROI were based on the left A1 areas of all subjects, the main activating area in the control group was bilateral superior temporal gyrus(STG), while the post-lingual deafness group included the bilateral STG, pre-central gyri, left Transverse temporal gyrus(TTG), post-central gyri and right TTG (P<0.01); when ROI were based on the right A1 areas of all subjects, the main activating area in the control group was the bilateral STG, while the post-lingual deafness group included the bilateral STG, right precentral gyri and post-central gyr i(P<0.01). The data showed statistical significance(P<0.05). Conclusion: After hearing loss functional reorganization takes place in the brains of adults with post-lingual deafness, resulting in possible enhancement of visual sense, tactile sense and other sensory systems in order to compensate information acquisition in daily life. .

[Epidemiological characteristics of molecular transmission cluster among reported HIV/AIDS cases in Jiaxing city, Zhejiang province, 2017].

Objective: To understand the epidemiological characteristics of one large HIV molecular transmission cluster in Jiaxing city, Zhejiang province, 2017 in order to select those people under high-risk and providing basis for programs on prevention. Methods: During 2017, newly diagnosed HIV/AIDS cases in this city were recruited. Plasma samples were collected from subjects, followed by RNA extraction, RT-PCR and nest-PCR for pol gene amplification, before being sequenced and aligned. Mega 6.0 software was used to construct phylogenetic tree, and Cytoscape 3.6.0 software was used to identify HIV molecular transmission clusters. Cases within the large transmission clusters were investigated, using a field-epidemiology-questionnaire. Data related to socio-demographics and previous sexual behaviors were collected and EpiData 3.0 and SPSS 20.0 software were used. Results: In the large transmission cluster with subtype identified as CRF07_BC, in Jiaxing, 2017, 26 cases of the total 30 cases were investigated. A total of 80.8% (21/26) could be identified as newly infected within the last two years and 30.8%(8/26) could be identified as newly infected within the last one year, including 22 cases infected locally. Among several infected cases who were at age 45 years or older, they admitted that they had experienced unprotected sexual contacts in local city for long time and having had more than 10 disclosed sexual contacts within the last two years at the local venues. Conclusions: This molecular cluster had been formed and scaled up quickly in recent two years, it has played an important role in promoting and scaling up the HIV transmission. Three cases identificed as high risk played an importantrde role in scaling up this cluster.

[Experimental study on dendritic cells modified by dust mite allergen gene in the treatment of allergic rhinitis in mouse].

Objective: To explore the therapeutic effects of dendritic cells (DC) modified by the dust-mite-allergen(Der p1) gene on mouse model of allergic rhinitis (AR). Methods: DC modified by the Der p1 gene (Der p1-DC) were prepared.Using random number table, 24 Balb\c mice were divided into four groups: immature DC (imDC)/AR group, dexamethasone/AR group, Der p1-DC/AR group and control group, with 6 mice in each group.AR mouse model was built with Der p1 and the mouse model of AR was established.The AR mice were respectively given by abdominal injection of Der p1-DC, imDC and dexamethasone.Normal control mice were treated with physiologic saline.ELISA method was used for determining the content of IgE, IgG1and histamine in blood.The relative expression of mRNA of IL-4 and IL-13 on nasal mucosa with protein was analyzed by RT-PCR and Westen blot methods.All the data were statistically analyzed by SPSS 19.0 statistical software, and the variance analysis was used in multiple groups of average samples. Results: The contents of IgE, IgG1 and histamine in the mice of Der p1-DC/AR group were lower than those in imDC/AR group ((0.560±0.110) OD 450 nm vs (1.150±0.280) OD 450 nm, (0.690±0.054) OD 450 nm vs (0.920±0.125) OD 450 nm, (4 145±670) pg/ml vs (7 685±669) pg/ml, t value was 4.80, 4.14, 9.16, respectively, all P<0.05), and the expression of IL-4 and IL-13 on nasal mucosa in Der p1-DC/AR group was remarkedly lower than those in imDC/AR group (0.41±0.25 vs 1.59±1.02, 0.26±0.01 vs 1.10±0.09, t value was 2.75, 22.72, respectively, all P<0.05). There was no statistically significant difference between the mice treated with Der p1-DC and dexamethasone group. Conclusions: The results showed that Der p1-DC could reduce inflammation in AR mice and decrease the expression of IL-4 and IL-13. It suggested that Der p1-DC can be used in the immunotherapy of AR mouse.