Along with the spread of human immunodeficiency virus 1 (HIV-1) infection in the world and the emergence of drug-resistant viral strains, it is urgent to seek the novel potent therapies. Chemokine receptor 5 (CCR5) is one of the main coreceptors involved in the entry of HIV-1 into target cells. Nowadays, a number of CCR5 antagonists have been developed and some of them have progressed to clinical trials or been approved. Research progress has also been made in the CCR5-targeted gene therapy. This review summarizes the recent research progress on the CCR5-targeted drug and gene therapy.
CCR5 Receptor Antagonists ; HIV Infections ; drug therapy ; genetics ; metabolism ; pathology ; HIV-1 ; drug effects ; Humans ; Molecular Targeted Therapy ; methods ; Receptors, CCR5 ; deficiency ; genetics ; metabolism

Objective To explore the genetic mutation in neonates who failed to pass hearing screening.Methods A total of 111 cases of neonates who failed to pass hearing screening and were conifrmed sensorineural deafness by auditory brainstem evoked potential (ABR) were randomly selected. The heel blood was collected and DNA was extracted.GJB2, SLC26A4, and 11 mutation hotspots in mitochondria gene12SrRNA were tested. The relationship between degree of hearing loss and gene mutation was analyzed.Results In 111 neonates, mutation in deafness gene were found in 24 cases (21.6%) . Among them 14 cases (12.6%) hadGJB2 gene mutation including 5 cases of 235delC single heterozygous mutation, 5 cases of 235delC, and 1 case each of 299_300delAT compound heterozygous mutation, 235delC homozygous mutation, 299_300delAT single heterozygous mutation, 176_191del16 and 235delC compound heterozygous mutation, and 299_300delAT and 508_511dupAACG compound heterozygous mutation respectively. Ten cases (9.0%) hadSLC26A4 gene mutation including 2 cases of IVS7-2A>G single heterozygous mutation, 3 cases of 1226G>A single heterozygous mutation, 2 cases of 2168A>G single heterozygous mutation, and 3 cases of IVS7-2A>G and 2168A>G compound heterozygous mutation. Mitochondrial gene mutations were not detected. Conclusions Deafness gene mutation is detected in more than 1/5 neonates who failed to pass newborn hearing screening. GJB2 gene mutation is the most commons. The implementation of hotspots deafness gene detection can improve the diagnostic rate of deafness.

Objective To investigate the expression of paired box2(Pax2),proliferation cell nuclear antigen(PCNA) and cell apoptosis in steroid-sensitive and steroid-resistant groups with primary nephrotic syndrome(PNS) and to find out the action of Pax2 expression in PNS with steroid-resistance.Method The expressions of Pax2,PCNA were evaluated by immunohistochemistry and cell apoptosis by fluorescence micoscope.Results Pax2 expression in renal tubule had a positive correlation with PCNA expression in steroid-sensitive group.In steroid-resistant group,Pax2 expression had no correlation with PCNA.Pax2 had a negative correlation with cell apoptosis.Conclusions Pax2 proper expression facilitate PCNA expression and repair tubulointerstitial lesions in steroid-sensitive group.Renal tubular epithelial cell proliferation coordinated with cell apoptosis.Pax2 overexpression in steroid-resistant group lead to the decrease of cell proliferation and cell apoptosis and lead to the severe tubule lesions,which made to glucocorticoid resistance.

0.05).Attention,ability of calculation(MMSE items)and DS scores were negatively correlated with left amygdala volumes(r=-0.51～-0.57,P

Objective To investigate the interventional effect of multidimensional strategy to reduce the incidence of neonatal ventilator-associated pneumonia.Methods The patients who were admitted to the NICU department and received mechanical ventilation (MV) for more than 48 hours from October 2012 to September 2014 were recruited. The control group received the experienced interventions from October 2012 to September 2013, neonates from October 2013 to September 2014 were recruited as the intervention group receiving multidimensional controlling strategy, including bundle care, education, pro-cess and outcome surveillance and feedback on the practices. The compliance of before-after implementation of interventions were quantitatively evaluated,and the rate of VAP was compared between the two groups.Results The compliance rate of hand hygiene and the qualiifed rate of sputum suction, oral care, drain condensation from ventilator circuit, semi-recumbent posi-tion, and preventing of stress-ulcers were increased 17.0%, 11.4%, 14.7%, 18.2%, 37.5% and 56.3% respectively after implemen-tation of multidimensional strategy, and had statistical difference (χ2=36.47-294.36,P<0.01). But the qualiifed rate of antibiotic use only was 66.1% in the post-VAP bundle phases, and showed no statistical difference before and after(P>0.05). The VAP rate was 41.7 cases per 1000 MV-days during control group and 19.7 cases per 1000 MV-days during intervention group, had statis-tical signiifcance (P<0.05). But the rate of ventilator application showed no statistical difference between two group (P>0.05). ConclusionThe multidimensional strategy can effectively prevent the incidence of VAP.

Objective To explore the impact of berberine on serum levels of insulin resistance and cytokines in schizophrenia patients treated with risperidone. Methods Sixty-four schizophrenia patients treated with risperidone were randomized to berberine group (n=31) and control group (n=33). The fasting plasma blood glucose (FBG) and fasting insulin (Fins) were detected before and after treatment in two groups. The homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. The serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α) were evaluated by enzyme linked immunosorbent assay before and after the treatment. Results Compared with control group and pre-treatment group, the levels of FBG, Fins, HOMA-IR, IL-1β, IL-6 and TNF-α were significantly decreased after treatment in berberine group (P<0.05). The FBG level was significantly higher, the levels of IL-1β, IL-6 and TNF-αwere significantly lower, after treatment in control group (P < 0.01). There were no significant changes in Fins and HOMA-IR after treatment (P > 0.05). There was positive correlation between HOMA-IR and IL-1β, IL-6 and TNF-α in berberine group (r=0.316, 0.351 and 0.401, P<0.01). Conclusion Berberine can significantly decrease FBG, Fins, HOMA-IR, IL-
1β, IL-6 and TNF-α levels in schizophrenia patients treated with risperidone. The HOMA-IR level is closely correlated with IL-1β, IL-6 and TNF-αlevels.

Objective To investigate the syndrome types of traditional Chinese medicine ( TCM) in senile hypertension patients by cluster analysis. Methods Case report sheet for senile hypertension was formed, and then the general data and TCM syndrome information of 495 cases of senile hypertension were recorded. The frequency of syndrome information of the enrolled cases was analyzed, and then the syndrome types were classified by cluster analysis. Results The symptoms with high frequency in senile hypertension patients were dizziness ( 75.9%) , insomnia ( 33.1%) , chest distress ( 29.9%) , poor appetite ( 23.2%) , headache (22.4%), slippery pulse (54.9%), greasy fur (51.7%), stringy pulse (49.7%), and white fur (47.8%) . The main syndrome patterns of 495 cases of senile hypertension were upward hyperactivity of liver yang (23.8%), Qi deficiency and phlegm turbidity (21%), kidney qi deficiency (19.8%), phlegm blended with blood stasis (18.4%), and phlegm heat (17.0%) . Conclusion Senile hypertension patients are dominated with the syndrome types of upward hyperactivity of liver yang, Qi deficiency and kidney deficiency, and are usually complicated with phlegm turbidity, phlegm heat and blood stasis. The complicated syndromes of phlegm turbidity and blood stasis are commonly-seen. The results of cluster analysis are expected to supply evidence for the syndrome differentiation of senile hypertension.

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly malignancies world-wide,with many patients failing to benefit sustainably from emerging immunotherapies and targeted thera-pies due to drug resistance.Current commonly used biomarkers,such as alpha-fetoprotein (AFP ),tumor mutation burden (TMB),and programmed cell death protein 1 (PD-1),lack efficacy in indica-ting the outcomes of HCC immunotherapy and targeted therapy.Therefore,identifying effective biomark-ers to accurately predict therapeutic efficacy is crucial for optimizing clinical decision-making.Recent studies have shown that N6-methyladenosine (m6 A) modification,one of the most common and important RNA modifications in eukaryotes,plays a significant role in the HCC resistance to immunotherapy and targeted therapy.We summarize the research progress regarding to the roles and mechanisms of m6 A modification and its functional proteins in the resistance to immunotherapy and targeted therapy in HCC,and also discuss the potential application of m6 A modification as biomarkers for predicting the efficacy of these treatments.

Objectives To investigate the clinical features,prognosis and risk factors of patients with cryptococcal meningitis.Methods Totally 146 patients with cryptococcal meningitis who were hospitalized in Huashan Hospital from January 2000 to December 2006 were enrolled in this study.The clinical data including diagnosis and misdiagnosis,experimental and etiology tests,treat- ments and prognosis from all the patients were analyzed retrospectively.Results Among the 146 patients enrolled in the study,78 patients(53.4%)had concomitant diseases.The misdiagnosis rate of all patients was 72.6%(106/146).The positive rate of cerebrospinal fluid(CSF)India ink smear was 59.6%(87/106),while 43.2%(63/146)cases of cryptococcus neoformans culture in CSF was positive.The positive rate of Latex agglutination test(LAT)was 91.7%(134/146)in CSF among all patients.The treatments were as follows:combination of Amphotericin B(AmpB)or its lipid formula- tions with flucytosine(5-FC)(98 cases),including combination with Fluconazole initally(62 cases), single therapy of Fluconazole(13 cases).Ommaya implanted for lateral cerebral ventricle drainage(53 cases)and AmpB intrathecal injection(53 cases).The average dose of AmpB is 3.06 g.The course of treatment lasted from 12 weeks to 20 months.There were 104 patients(71.2%)cured,27(18.5%) improved,15(10.3%)died and 34(23.3%)relapsed.Conclusions High misdiagnosis rate is common in patients with cryptococcal meningitis.Immunodeficiency is the major risk factor for cryp- tococcal meningitis.CSF LAT is the most sensitive diagnostic test.Early diagnosis,combination of AmpB with 5-FC antifungal therapy and control of acute intracranial hypertension are the keys to im- prove prognosis of cryptococcal meningitis.

To study the effect of Wansheng Huafeng Dan (WSHFD) and mercuric chloride on renal mercury (Hg) extraction transporters (Oat1, Oct2), renal mercury excretion transporters (Mrp4, Mate2K), renal mercury accumulation and kidney injury molecule-1 (Kim-1). The ancient prescription of WSHFD containing 10-fold Hg caused much lower renal mercury accumulation and renal toxicity than HgCl2 in rats, with less effect on renal transporters than HgCl2. The above indicators had no significant difference in WSHFDO, WSHFD2 and WSHFD3 groups, indicating no effect of WSHFD with reduced or no cinnabar.
Animals ; Ardisia ; chemistry ; Biological Transport ; drug effects ; Cell Adhesion Molecules ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Gene Expression ; drug effects ; Kidney ; drug effects ; metabolism ; Male ; Mercuric Chloride ; metabolism ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley