PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study / 亚洲男科学杂志(英文版)

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.

Exosomes secreted by chemoresistant ovarian cancer cells promote angiogenesis.

BACKGROUND: Ovarian cancer (OC) has the highest mortality rate in gynecologic tumors. Despite decades of continuous efforts, the survival rate of patients has not improved significantly, mostly due to drug resistance. Exosomes are hot topics in recent years. Cells can affect the biological behaviors of other cells by transferring exosomes. So far, numerous researchers have found that tumor cells can secrete exosomes which play a important role in the development of tumors. Solid tumors can promote angiogenesis. When drug resistance occurs, it seems that more blood vessels form. We suppose that exosomes derived from chemoresistant OC cells can also promote angiogenesis. RESULTS: We investigate whether exosomes secreted by chemoresistant SKOV3-DDP cells (SKOV3-DDP-exo) and sensitive SKOV3 cells (SKOV3-exo) influence angiogenesis. After exosomes were extracted, exosomes were co-cultured with HUVECs. We found that SKOV3-DDP-exo and SKOV3-exo are absorbed by endothelial cells and promote the proliferation, migration, invasion and tube formation of endothelial cells. Moreover, SKOV3-DDP-exo is more powerful in angiogenesis, suggesting that parts of the components of SKOV3-DDP-exo are significantly radical. We also found that miR-130a was highly expressed in drug-resistant OC cells. Also, we found that miR-130a in SKOV3-DDP-exo is higher than SKOV3-exo. Therefore, we suggest that miR-130a in exosomes is the main cause of chemoresistant OC cells promoting angiogenesis.

PET/CT for guidance of lymphadenectomy of high-risk prostate cancer in patients with chronic lymphocytic leukemia: 1 case report / 上海交通大学学报（医学版）

A 70-year-old male with chronic lymphocytic leukemia (CLL) 9 years ago initially presenting elevation of prostate specific antigen (PSA) was diagnosed with high-risk prostate cancer in March, 2018. He received 18F-FDG positron emission tomography/computed tomography (PET/CT), which showed mild FDG-avidity in swollen lymph nodes across the entire body, considering CLL. Then he underwent neoadjuvant androgen deprivation therapy for 1 month and then robot-assisted radical prostatectomy and biopsy of the right iliac vascular obturator lymph nodes. The prostate pathology was prostate cancer, and the pathology of lymph nodes was CLL. His serum PSA levels 1 month and 3 months after operation both reached the level of cure. For the patients with concomitant high-risk prostate cancer and CLL, PET/CT may be valuable in distinguishing whether the swollen lymph nodes were infiltrated by prostate cancer and guiding the lymphadenectomy.

Effects of HPV Pseudotype Virus in Cutting E6 Gene Selectively in SiHa Cells / 华中科技大学学报（医学）（英德文版）

The objectives of this study were to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudotype virus on SiHa cytobiology behavior by cutting the HPV16 E6 gene selectively and to explore the role of this system in the treatment of cervical cancer.After designing specific gRNA sequences targeting HPV 16 E6,generating hCas9-EGFP and E6-gRNA-RFP plasmids,and preparing the pseudovirus of HPV16 carrying E6-gRNA and Cas9 plasmids,we determined the titer of the pseudotype virus using the TCID50 method.We obtained the pseudotype virus of HPV16 carrying E6-gRNA and Cas9 plasmids to transfect cervical cancer SiHa cells.Experimental subjects were divided into control group,empty virus group,E6-gRNA transfected group,Cas9 transfected group and Cas9+E6-gRNA transfected group.The molecular size of the cutting sequence was detected using the T7E1 enzyme digestion method and agarose gel electrophoresis,and the cleavage function of CRISPR/Cas9 on the E6 gene was determined at the same time.RT-PCR and Western blotting were performed to detect the mRNA and protein expression levels of E6 in all the groups;the Transwell cell migration assay was performed to detect the cell migration ability and metastasis in all groups.Heterotopic transplantation tumors were incorporated into mice and were used to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudovirus on the tumorigenic ability of SiHa cells by selectively cutting HPV16 E6.The HPV16 pseudotype virus carrying E6-gRNA and Cas9 plasmids could successfully infect SiHa cells,and there were two cutting zones in the Cas9+E6-gRNA transfected group.However,the empty virus group,E6-gRNA transfected group and Cas9 transfected group had no corresponding zone.Compared with those in the control group,the empty virus group,E6-gRNA transfected group and Cas9 transfected group,the mRNA and protein expression levels of E6 in SiHa cells were downregulated in the Cas9+E6-gRNA transfected group (P＜0.01).In addition,the proliferation and migration abilities of SiHa cells were significantly inhibited (P＜0.01).There were no significant differences among the other groups.In contrast to the control group,the HPV pseudotype virus carrying E6-gRNA and Cas9 plasmids could significantly delay the growth of tumor cells of the ectopic tumor transplantation model (P＜0.01).The CRISPR/Cas9 system mediated by the HPV pseudotype virus to knockout E6 gene expression exhibited a clear inhibitory effect on the biological function of SiHa cells,which indicated that knocking out the E6 gene using the CRISPR/Cas9 system mediated by the HPV pseudotype virus had a potential effect of eliminating HPV infection and inhibiting the growth of HPV-related tumors.Taken together,these findings provide insight into a new treatment strategy for the prevention and treatment of hr-HPV infected disease,particularly in HPV-related tumors.

Peripheral Leptin Signaling Mediates Formalin-Induced Nociception / 神经科学通报·英文版

Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a high-fat diet, we found that: (1) the acute thermal pain sensory threshold did not change in obese mice; (2) the model obese mice had fewer nociceptive responses in formalin-induced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation; (3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice, indicating the dysmodulation of topical leptin-leptin receptor signaling in these mice; and (4) leptin-leptin receptor signaling-deficient mice (ob/ob and db/db) or leptin-leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wild-type mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin-leptin receptor pathway could be a peripheral target against acute inflammatory pain.

Effects of HPV Pseudotype Virus in Cutting E6 Gene Selectively in SiHa Cells / 华中科技大学学报（医学）（英德文版）

The objectives of this study were to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudotype virus on SiHa cytobiology behavior by cutting the HPV16 E6 gene selectively and to explore the role of this system in the treatment of cervical cancer.After designing specific gRNA sequences targeting HPV 16 E6,generating hCas9-EGFP and E6-gRNA-RFP plasmids,and preparing the pseudovirus of HPV16 carrying E6-gRNA and Cas9 plasmids,we determined the titer of the pseudotype virus using the TCID50 method.We obtained the pseudotype virus of HPV16 carrying E6-gRNA and Cas9 plasmids to transfect cervical cancer SiHa cells.Experimental subjects were divided into control group,empty virus group,E6-gRNA transfected group,Cas9 transfected group and Cas9+E6-gRNA transfected group.The molecular size of the cutting sequence was detected using the T7E1 enzyme digestion method and agarose gel electrophoresis,and the cleavage function of CRISPR/Cas9 on the E6 gene was determined at the same time.RT-PCR and Western blotting were performed to detect the mRNA and protein expression levels of E6 in all the groups;the Transwell cell migration assay was performed to detect the cell migration ability and metastasis in all groups.Heterotopic transplantation tumors were incorporated into mice and were used to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudovirus on the tumorigenic ability of SiHa cells by selectively cutting HPV16 E6.The HPV16 pseudotype virus carrying E6-gRNA and Cas9 plasmids could successfully infect SiHa cells,and there were two cutting zones in the Cas9+E6-gRNA transfected group.However,the empty virus group,E6-gRNA transfected group and Cas9 transfected group had no corresponding zone.Compared with those in the control group,the empty virus group,E6-gRNA transfected group and Cas9 transfected group,the mRNA and protein expression levels of E6 in SiHa cells were downregulated in the Cas9+E6-gRNA transfected group (P＜0.01).In addition,the proliferation and migration abilities of SiHa cells were significantly inhibited (P＜0.01).There were no significant differences among the other groups.In contrast to the control group,the HPV pseudotype virus carrying E6-gRNA and Cas9 plasmids could significantly delay the growth of tumor cells of the ectopic tumor transplantation model (P＜0.01).The CRISPR/Cas9 system mediated by the HPV pseudotype virus to knockout E6 gene expression exhibited a clear inhibitory effect on the biological function of SiHa cells,which indicated that knocking out the E6 gene using the CRISPR/Cas9 system mediated by the HPV pseudotype virus had a potential effect of eliminating HPV infection and inhibiting the growth of HPV-related tumors.Taken together,these findings provide insight into a new treatment strategy for the prevention and treatment of hr-HPV infected disease,particularly in HPV-related tumors.

Peripheral monocyte count: An independent diagnostic and prognostic biomarker for prostate cancer-A large Chinese cohort study / 亚洲男科学杂志(英文版)

Increasing evidence indicates that inflammation may play important roles in tumorigenesis and progression, and an elevated peripheral monocyte count predicts a poor prognosis in various types of malignancies. Here, we evaluate the roles of peripheral monocyte count in the diagnosis and prognosis for prostate cancer in Chinese patients. A total of 1107 consecutive patients who had undergone prostate biopsy and 290 prostate cancer patients receiving androgen deprivation therapy as first-line therapy were retrospectively analyzed. The parameters were measured at the time of diagnosis. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors of a positive biopsy. Patients were categorized in two groups using a cutoff point of 0.425 × 109 l-1 as calculated by the receiver-operating curve analysis for prognosis. Univariate and multivariate Cox regression analyses were performed to determine the associations of monocyte count with progression-free survival, cancer-specific survival, and overall survival. Multivariate logistic regression analyses showed that monocyte count, age, prostate-specific antigen (PSA), free/total PSA, and prostate volume were independent predictors for prostate cancer. Multivariate Cox regression analyses identified an elevated monocyte count as an independent prognostic factor for worse cancer-specific survival (hazard ratio = 2.244, P < 0.05) and overall survival (hazard ratio = 1.995, P < 0.05), but not progression-free survival (P = 0.117). Our results indicated that an elevated monocyte count was an independent diagnostic biomarker for prostate cancer, and pretreatment peripheral monocyte count might play a significant role in the prognosis of prostate cancer patients treated with androgen deprivation therapy.

Meta analysis about the efficacy and safety of anti-ocular hypertension eye drops without benzalkonium chloride

OBJECTIVE@#To explore the safety and efficacy of eye drops without benzalkonium chloride (BAK) in treating glaucoma and ocular hypertension.@*METHODS@#The clinical case-control literatures about eye drops without BAK treating glaucoma and ocular hypertension were retrieved in PubMed, EMBASE, Cochrane and Chinese Biological and Medical database. Meta 5.0 software was used to analyze the literatures.@*RESULTS@#Five clinical control studies were included. The results indicated both eye drops could lower the intraocular pressure, and the intraocular pressure-lowering difference between two eye drops was 0.07 mmHg (95% CI: 0.04, 0.19) (P>0.05). Two adverse reactions occurred more were conjunctival injection (10.78%) and allergic conjunctivitis (4.78%). The odd ratio of two eye drops occurring conjunctival injection and allergic conjunctivitis was 0.67 (95% CI, 0.25, 1.10) and 0.82 (95% CI, 0.09, 1.54), respectively (P<0.05) in fixed effect model.@*CONCLUSIONS@#There is no difference between the eye drops with or without BAK in lowering intraocular pressure, but the latter is of higher safety. In consideration of the relatively small sample size of this research, more high-quality clinical research contrasts are needed as evidence.

Spectral studies on the interaction between Cu2+ and urease.

The interactions of Cu(2+) with urease were investigated by fluorescence, UV/vis, CD, synchronous fluorescence, and three-dimensional fluorescence spectra techniques. Cu(2+) effectively quenched the intrinsic fluorescence of urease via static quenching. The binding constant K(A), the binding site n and the thermodynamic parameters are obtained. The process of binding Cu(2+) to urease was a spontaneous molecular interaction procedure with electrostatic interaction. The conformation of urease was discussed by UV/vis, CD, synchronous and three-dimensional fluorescence techniques.

Epidemiologic study on patients with invasive fungal infectious / 中华流行病学杂志

Objective To investigate the epidemiological features of patients with nosoeomial invasive fungal infection. Methods Fungi in blood were identified by BaeT ALERT 3D, other clinical samples were cultured by Sabouraud' s dextrose agar (SDA) medium. Candidas were isolated and identified by CHRO Magar candida color medium. Fungus-cultured positive cases from Jan. 2004 to Nov. 2007 were analyzed on items as patients' age, underlying disease, sample, strain, and species distribution. All statistical analyses were carried out by SPSS 13.0. Results The overall incidence rate of invasive fungal infections was 4.12%. The average age of patients was 7-96 with most patients were male, with geriatric problems and different kinds of underlying diseases. Lower respiratory tract infection was the most frequent infection site, followed by urinary tract, gastrointestinal tract. The main pathogens of invasive fungal infections were Candidas (93.80%). Strains of Candida albicans were the most frequent organisms which accounted for 67.29% of all the isolates. Mould fungus infections accounted for only 6.20%. During the 4 years of observation, the detection rate of fungi, specimen sources and the distribution of species and compartment were different with significant differences (P<0.0083). Conduslon The epidemiological properties such as the source of specimen, the distribution of species and composition sections of invasive fungal infections were changing. Candida slaP. were still the main pathogens of invasive fungal infections but the sections of fungi changed. The incidence of Aspergillus infections had been increasing recently.

Is functional state of spinal microglia involved in the anti-allodynic and anti-hyperalgesic effects of electroacupuncture in rat model of monoarthritis?

Spinal microglia play a key role for creating exaggerated pain following tissues inflammation or injury. Electroacupuncture (EA) can effectively control the exaggerated pain both in humans with inflammatory disease and animals with experimental inflammatory pain. However, little is known about the relationship between spinal glial activation and EA analgesia. Using immunohistochemistry, RT-PCR analysis, and behavioral testing, the present study demonstrated that (1) Unilateral intra-articular injection of CFA produced a robust microglial activation and the up-regulation of the tumor necrosis factor (TNF)-alpha, interleukin (IL-1beta), and IL-6 mRNA levels in the spinal cord; (2) Repeated intrathecal (i.t.) injection of minocycline (100 microg), a microglial inhibitor, or EA stimulation of ipsilateral "Huantiao"(GB30) and "Yanglingquan" (GB34) acupoints significantly suppressed CFA-induced nociceptive behavioral hypersensitivity and spinal microglial activation; (3) Combination of EA with minocycline significantly enhanced the inhibitory effects of EA on allodynia and hyperalgesia. For the first time, these data provide direct evidence for the involvement of spinal microglial functional state in anti-nociception of EA. Thus, anti-neuroinflammatory effect of EA might be considered as one of the mechanisms of its anti-arthritic pain effects, and thereby a multidisciplinary integrated approach to treating symptoms related to arthritis might be raised.

A digital tongue image analysis instrument for Traditional Chinese Medicine / 中国医疗器械杂志

A digital tongue image analysis instrument (TIAI) based on computer for Traditional Chinese Medicine is introduced. Some of the key techniques, including the image acquiring condition and method, the evaluation of tongue characters, and the management of tongue image data, are discussed as well. TIAI can provide a non-invasive, quantitative, and objective analysis approach and enhance the theory level and practical ability of the Traditional Chinese tongue diagnosis.