Covid-19 Study, Diagnostic and Therapeutic Transition.

INTRODUCTION: The outbreak of coronavirus (severe acute respiratory syndrome coronavirus2, COVID-19, SARS-Co-2) in Wuhan, China occurred three years ago. However, the healthcare state and legislature for Covid-19 varied greatly worldwide. AIMS: After three years, the social life of most countries worldwide is gradually back to normal. Diagnosis and therapeutics worldwide are formalized now. Improvement of the knowledge about this devastating disease will shed new light on its management and spawn the development of new counter measures. Due to the differences in socioeconomic conditions and policies worldwide, the diagnostic and therapeutic transition should be established. METHODS: The schedules and techniques of vaccines, drugs, or other therapeutic strategies could be formalized in the future. The origin and hidden nature of Covid-19 biology (relationship between viral strain and drug targeting) should be further investigated. Knowledge and opinion breakthroughs may significantly heighten the quality of preventive and therapeutic strategies against Covid-19. RESULTS: To further stabilize the global situation, the issues of viral spread and induced mortality should be emphasized. Existing animal models, pathophysiological knowledge, and therapeutics for different infected patients played vital roles. The diagnostic widening, variants of COVID, and therapeutic selection worldwide totally solve the complex outcomes and promote the curability for infected patients. DISCUSSION: Different diagnostic platforms can reach different therapeutic selections, responses, and benefits in the clinic. It will provide advanced diagnostic dimensions, therapeutic paradigms, and drug selection strategies for the purpose of the greatest benefiting and recoveries of Covid-19 patients. CONCLUSION: To speed up the global fight against Covid-19, biomedical knowledge, prophylactic vaccines, and therapeutic paradigms should be updated in dynamic states.

HIV/AIDS Curability Study, Different Approaches and Drug Combination.

AIM: HIV infection is currently an incurable disease characterized by life-long drug utility. Its incurable causality and mechanism are still unknown to us. METHODS: To overcome this therapeutic setback, some breakthroughs should be made by utilizing different approaches. How to plan some experimental and clinical novelty for HIV curability is a modern challenge. In this article, new ideas and approaches for global HIV/AIDS therapeutic strategies are proposed and represented by scientific insights. RESULTS: Pharmaceutical characteristics, herbal medicine, novel drug targets, cutting-edge biotherapy, drug combination, animal modalities, and immune-stimuli for HIV latency, as well as clearance, are highlighted. DISCUSSION: To elucidate our understanding of curative treatment for HIV/AIDS, many new pathological discoveries, expansion, technical advances, and potential drug targets are constructed. After the discovery of novel pathogenesis and therapeutic evolution, HIV/AIDS therapeutic curability may become achievable and a reality. CONCLUSION: Transformation from animal model investigation to widespread therapies for larger volume of human population is a necessity in modern medicine. In this infectious treatment scenario, major breakthroughs in medicine and drug development are anticipated.

Drug Sensitivity Testing for Cancer Therapy, Technique Analysis and Trends.

The techniques and qualities of drug sensitivity testing (DST) for anticancer treatment have grown rapidly in the past two decades worldwide. Much of DST progress came from advanced systems of technical versatility (faster, highly-throughput, highly-sensitive, and smaller in tumor quantity). As the earliest drug selective system, biomedical knowledge and technical advances for DST are mutually supported. More importantly, many pharmacological controversies are resolved by these technical advances. With this technical stride, the clinical landscape of DST entered into a new phase (>500 samples per testing and extremely low quantity of tumor cells). As a forerunner of the drug selection system, DST awaits a new version that can adapt to complicated therapeutic situations and diverse tumor categories in the clinic. By upholding this goal of pathogenic and therapeutic diversity, DST could eventually cure more cancer patients by establishing high-quality drug selection systems. To smoothen DST development, there is a need to increase the understanding of cancer biology, pathology and pharmacology (cancer heterogeneity, plasticity, metastasis and drug resistance) with well-informative parameters before chemotherapy. In this article, medicinal and technical insights into DST are especially highlighted.

Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis / 中国中药杂志

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1β, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

Therapeutic effect and mechanism of Xiaoyao Kangai Jieyu Recipe on mice with breast cancer related depression through regulating COX pathway / 中国中药杂志

This study aimed to investigate the intervention effect and mechanism of Xiaoyao Kangai Jieyu Recipe(XKJR) on hip-pocampal microglia and neuronal damage in mice with breast cancer related depression. The mouse model of breast cancer related depression was established by inoculation of 4T1 breast cancer cells in axilla and subcutaneous injection of corticosterone(30 mg·kg~(-1)). The successfully modeled mice were randomly divided into a model group, a positive drug group(capecitabine 60 mg·kg~(-1)+fluoxetine 19.5 mg·kg~(-1)), and XKJR group(19.5 mg·kg~(-1) crude drug), with 6 in each group. Another 6 normal mice were taken as a normal group. The administration groups were given corresponding drugs by gavage, while the normal and model groups were given an equal volume of distilled water, once a day for 21 consecutive days. The depressive behavior of mice was assessed by glucose consumption test, open field test and novelty-suppressed feeding test. Hematoxylin and eosin(HE) staining and tumor suppression rate were used to evaluate the changes of axillary tumors. The mRNA expressions and the relative protein expressions of interleukin-1β(IL-1β), interleukin-18(IL-18), cyclooxyganese-2(COX-2) and glutamyl-prolyl-tRNA synthetase(EPRs) in the hippocampus of mice were determined by quantitative real-time polymerase chain reaction(qRT-PCR) and immunohistochemistry, respectively. Immunofluorescence was performed to detect the mean fluorescence intensity of CD11b, a marker of hippocampal microglia activation. Nissler staining and transmission electron microscopy were employed to observe the morphological changes and the ultramorphological changes of hippocampal neurons, respectively. The experimental results indicated that compared with the normal group, the model group had reduced glucose consumption and lowered number of total activities in open field test(P<0.05, P<0.01), prolonged first feeding latency in no-velty-suppressed feeding test(P<0.01), and significant depression-like behavior; the contents of IL-1β, IL-18, COX-2, and EPRs in hippocampus were increased(P<0.05, P<0.01), with hippocampal microglia activation and obvious neuronal damage. Compared with the model group, the positive drug group and the XKJR group presented an improvement in depressive behaviors, a decrease in the contents of IL-1β, IL-18, COX-2 and EPRs in hippocampus, and an alleviation in the activation of hippocampal microglia and neuronal damage; the tumor suppression rates of positive drug and XKJR were 40.32% and 48.83%, respectively, suggesting a lower tumor growth rate than that of the model group. In summary, XKJR may improve hippocampal microglia activation and neuronal damage in mice with breast cancer related depression through activating COX signaling pathway.

Two new ursane triterpenoids from Agastache rugosa (Fisch. et.Mey.) O. Kuntze / 药学学报

Two new ursane triterpenoids along with twelve known compounds were isolated from 80% ethanol extract of Agastache rugosa (Fisch. et. Mey.) O. Kuntze by using silica gel column, MCI column, ODS column and HPLC. The structures of the new compounds were identified as 2α,3α-dihydroxy-24-nor-urs-4(23),12(13)-dien-28-oic acid (1) and 2α,3α-dihydroxy-24-nor-urs-4(23),12(13),20(30) -trien-28-oic acid (2) by HR-ESI-MS, NMR and ECD spectral data, named agasursacid A and agasursacid B. In addition, compounds 3, 4, 6, 8 showed anti-coxsackievirus B3 (CVB3) activities with a IC50 as 4.77, 1.59, 11.11 and 25.87 μmol·L-1, resepectively.

Drug Sensitivity Testing for Cancer Therapy, Key Areas.

AIMS: Cancer is a high-mortality disease (9.6 million deaths in 2018 worldwide). Given various anticancer drugs, drug selection plays a key role in patient survival in clinical trials. METHODS: Drug Sensitivity Testing (DST), one of the leading drug selective systems, was widely practiced for therapeutic promotion in the clinic. Notably, DSTs assist in drug selection that benefits drug responses against cancer from 20-22% to 30-35% over the past two decades. The relationship between drug resistance in vitro and drug treatment benefits was associated with different tumor origins and subtypes. Medical theory and underlying DST mechanisms remain poorly understood until now. The study of the clinical scenario, sustainability and financial support for mechanism and technical promotions is indispensable. RESULTS: Despite the great technical advance, therapeutic prediction and drug selection by DST needs to be miniature, versatility and cost-effective in the clinic. Multi-parameters and automation of DST should be a future trend. Advanced biomedical knowledge and clinical approaches to translating oncologic profiles into drug selection were the main focuses of DST developments. With a great technical stride, the clinical architecture of the DST platform was entering higher levels (drug response testing at any stage of cancer patients and miniaturization of tumor samples). DISCUSSION: The cancer biology and pharmacology for drug selection mutually benefit the clinic. New proposals to reveal more therapeutic information and drug response prediction at genetic, molecular and omics levels should be estimated overall. CONCLUSION: By upholding this goal of non-invasive, versatility and automation, DST could save the life of several thousand annually worldwide. In this article, new insights into DST novelty and development are highlighted.

Two new labdane diterpenoids from the leaves of Callicarpa formosana Rolfe / 药学学报

Two new labdane diterpenoids were isolated from 95% ethanol extract of the leaves of Callicarpa formosana Rolfe by using silica gel column, MCI column, ODS column and HPLC. Their structures were elucidated by HR-ESI-MS, NMR and ECD spectral data. All of them are new compounds, named 13E-6β-hydroxylabda-8(17),13-dien-15-oic acid (1) and 13E-7α-hydroxylabda-8(17),13-dien-15-oic acid (2). Compounds 1 and 2 were tested for antioxidant activity, and none of them had obvious activity.

Effect of conversion of tacrolimus dosage forms from immediate-release to extended-release on kidney function in stable kidney transplant recipients / 中华器官移植杂志

Objective:To observe the effect of conversion from immediate-release tacrolimus (Tac) to extended-release Tac on kidney function in stable kidney transplant recipients.Methods:83 stable kidney transplant recipients who were converted from immediate-release Tac to extended-release Tac in the second people's hospital of Shanxi province from December 2011 to June 2019 were followed up for 12-36 months, and 83 stable kidney transplant recipients who continued to take immediate-release Tac were selected as control group.The changes of kidney function indexes, Tac trough concentration intra-patient variability (IPV) and compliance, the incidence of rejection and the survival rate of grafts and recipients were observed after the conversion from immediate-release Tac to extended-release Tac in stable kidney transplant recipients.Results:The conversion time from immediate-release Tac to extended-release Tac was (42.76±30.50)months after transplantation. At 24 months after conversion, the serum creatinine (SCr) was significantly lower than that before conversion ( P=0.013), and the estimated glomerular filtration rate(eGFR)was significantly higher than that before conversion( P=0.005). In the experimental group , the SCr was significantly lower than that of the control group at 36 months after conversion ( P= 0.017), eGFR was significantly higher than that of the control group ( P=0.038). In the experimental group, the score of Immunosuppressant Therapy Barrier Scale (ITBS) was (20.23±2.89) before conversion and (17.63 ±3.08) after conversion ( P= 0.000). The daily dose of Tac was (2.09 ±0.84) mg before conversion and (2.10 ±0.83) mg after conversion. The trough concentration of Tac before conversion was (7.22 ±2.84) ng/mL, which reduced significantly after conversion. No rejection occurred after conversion, and the recipients/grafts survived healthily during the follow-up period. Conclusions:After conversion from immediate-release Tac to extended-release Tac in stable kidney transplant recipients, the kidney function is stable and better than that of before conversion, the compliance is significantly improved, the IPV of Tac trough concentration is significantly reduced, and long-term use of extended-release Tac has good clinical efficacy and safety.

Antiviral effects of selected IMPDH and DHODH inhibitors against foot and mouth disease virus.

Foot-and-mouth disease virus (FMDV) is an important pathogen that affects livestock breeding and causes huge economic losses worldwide. Currently, the development of antiviral agents to combat FMDV infection at the early stages is being explored. As viral replication critically depends on the host for nucleoside supply, host enzymes involved in nucleotides biosynthesis may represent potential targets for the development of antiviral agents. In the present study, the effects of IMP dehydrogenase (AVN-944 and mycophenolate mofetil) and dihydroorotate dehydrogenase (teriflunomide) inhibitors were evaluated both in vitro and in vivo. The results revealed that these compounds were effective in suppressing FMDV (O/MY98/BY/2010 and A/GD/MM/2013) infection. With regard to the antiviral mechanism, time-of-addition experiments revealed that these compounds were effective when added at the early stages of viral lifecycle (0-8 h post infection). However, exogenous guanosine/uridine eliminated the antiviral activity of these compounds. Importantly, treatment AVN-944 and teriflunomide significantly improved the survival of mice that were subcutaneously treated with FMDV. Together, the results of the present study indicate the broad-spectrum activities of anti-FMDV agents targeting IMP dehydrogenase or dihydroorotate dehydrogenase, which could be useful in developing strategies to prevent FMD.

Pharmacological and psychological interventions for generalized anxiety disorder in adults: A network meta-analysis.

Generalized anxiety disorder (GAD) is a significant and common mental illness with a lifetime prevalence of 3.7%. Regardless of the complexity of treatment decisions for GAD, few studies have conducted systematic comparisons of the efficacies of varying interventions. Thus, this study performed a valid network meta-analysis (NMA) of randomized controlled trials (RCTs) to synthesize direct and indirect evidence for alternative interventions for GAD. We searched four major bibliographic databases, the Cochrane Central Register of Controlled Trials, Embase, PsycINFO, and PubMed, for published RCTs of adult patients with a diagnosis of GAD and allowed for all comorbidities. A total of 91 articles (14,812 participants) were identified in the final NMA. The results showed that all pharmacological treatments except for serotonin modulators and second-generation antipsychotics had greater effects than placebo: norepinephrine-dopamine reuptake inhibitors (standardized mean difference (SMD) -1.84, 95% credible interval -3.05 to -0.62), noradrenergic and specific serotonergic antidepressants (-0.91, -1.62 to -0.20), melatonergic receptor agonists (-0.68, -1.15 to -0.21), selective serotonin reuptake inhibitors (SSRIs; -0.67, -0.90 to -0.43), azapirones (-0.58, -1.00 to -0.17), anticonvulsants (-0.56, -0.85 to -0.28), serotonin-norepinephrine reuptake inhibitors (SNRIs; -0.54, -0.79 to -0.30), and benzodiazepines (BZDs; -0.40, -0.65 to -0.15). Most psychological and self-help interventions exerted greater effects than the waitlist group. However, no psychological interventions had greater effects compared with the psychological placebo. Overall, most pharmacological interventions had larger effect sizes than psychological interventions, and most psychological interventions showed larger effect sizes than self-help interventions.

RETRACTED: Human Suicide, Modern Diagnosis Assistance and Magic Bullet Discovery

The article entitled "Human Suicide, Modern Diagnosis Assistance and Magic Bullet Discovery", by Da-Yong Lu, Peng- Peng Zhu, Hong-Ying Wu, Nagendra Sastry Yarla, Bin Xu, Jian Ding, Ajit Varki and Ting-Ren Lu, has been retracted on the request of the co-authors, Dr. Ajit Varki, Dr. Nagendra Sastry Yarla and Dr. Jian Ding available at: Cent Nerv Syst Agents Med Chem 2019; 19(1): 15-23. http://www.eurekaselect.com/169003/article.The Corresponding Author Dr. Da-Yong Lu has included the names of the co-authors, Dr. Ajit Varki, Dr. Nagendra Sastry Yarla and Dr. Jian Ding without their consent and the manuscript has been published in the journal, Central Nervous System Agents in Medicinal Chemistry (CNSAMC). Kindly see Bentham Science Policy on Article retraction at the link given below:(https://benthamscience.com/journals/central-nervous-system-agents-in-medicinal-chemistry/author-guidelines/)Submission of a manuscript to the respective journals implies that all authors have read and agreed to the content of the Copyright Letter or the Terms and Conditions. As such, this article represents a severe abuse of the scientific publishing system. Bentham Science Publishers takes a very strong view on this matter and apologizes to the readers of the journal for any inconvenience this may cause.

Ebola Therapeutic Study and Future Directions.

The constant Ebola epidemic outbreaks in Africa arisen in waves of panic worldwide. There is a high mortality rate (30-70%) among the Ebola-infected people in virus- stricken areas. Despite these horrors, the medical capabilities against this deadly viral disease were provided by limited therapeutic agents/options. As a result, several patented agents, biotherapies or prophylactic/therapeutic vaccines need to be reviving into the global markets-including patents of small molecular chemicals, short sequences or oligomers of DNA/RNA, linkages of chemicals with bio-molecules, herbal medicine and so on. In addition, the possible mechanisms of action of these therapeutic options are underway. To promote Ebola biomedical study, the multiple characters of Ebola infections-its origin, pathologic progress, genomic changes, therapeutic context and economic considerations are outlined in this review. Finally, a great difference can be expected after these types of efforts.

Cerebral functional abnormalities in patients with nasopharyngeal carcinoma after radiotherapy: an observational magnetic resonance resting-state study / 中华医学杂志(英文版)

Background@#Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT.@*Methods@#From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups.@*Results@#After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P < 0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (P < 0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar–cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (P < 0.001, corrected by AlphaSim).@*Conclusions@#Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.

Personality and depression: A review of theory model and behavior and neural mechanism / 生理学报

The analysis of the relationship between personality and depression can facilitate the development of subclinical preventive measures and clinical treatment schemes. Moreover, the personality is associated with a variety of mental diseases, and there is substantial comorbidity between depression and some other mental diseases. So, to reveal pathological relationships between personality and depression is helpful to understand the etiology of the comorbidity between depression and multiple mental disorders. In this review, we first summarize the empirical researches on the relationship between personality and depression from the aspects of behavior and neural mechanisms, and then discuss the hypothetical model to explain the relationship between personality and depression. In a word, high neuroticism, low extroversion and conscientiousness, and other related traits (rumination, self-criticism, dependency, etc.) have a moderate to strong correlation with depression. Among them, neuroticism is the most concerned. To a certain extent, it can predict the onset of depression and affect the duration and treatment outcome of depression. Other traits, such as positive emotionality/ extroversion and effortful control/responsibility, can moderate the relationship between negative emotionality/neuroticism and depression. And after the onset of depression, the neuroticism may change, but the extroversion does not seem to change.

Cerebral functional abnormalities in patients with nasopharyngeal carcinoma after radiotherapy: an observational magnetic resonance resting-state study / 中华医学杂志(英文版)

BACKGROUND@#Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT.@*METHODS@#From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups.@*RESULTS@#After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P < 0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (P < 0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar-cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (P < 0.001, corrected by AlphaSim).@*CONCLUSIONS@#Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.

HIV/AIDS Curable Study: New Forms of Therapeutic Trinity.

BACKGROUND AND AIMS: AIDS (acquired immune deficient syndrome), a deadly human infectious disease is caused by HIV (human immunodeficiency viruses) infection. Patient's mortality was eventually reduced to one-fourth by combined chemotherapy (usually 3 chemical drugs simultaneously) than earlier HIV/AIDS treatments (single drug or vaccine) in the clinic. RESULTS: Combined treatments against HIV/AIDS are still incurable for all patients despite a high rate of patient's survival. Basic viral pathological study and advancing drug development systems for curable medications are indispensable nowadays and in the future. CONCLUSION: Up to date, therapeutic trinity (combined therapy) against HIV/AIDS is generally among chemical drugs. In this article, several forms of other therapeutic attempts for effectively curing efforts against HIV/AIDS are proposed-including the development of next generation therapeutic HIV vaccines and schedules, new categories of bio-therapy, different pathways of immune-modulation, herbal medicines in general (allopathic, Ayurveda and traditional Chinese medicines), high quality of physical exercises, and especially therapeutic combinations guided by latest medical discovery and principles (new forms of therapeutic trinity against HIV-induced pathogenesis and human mortality).

Human Suicide Risk and Treatment Study.

INTRODUCTION: Suicide is still a major event of human mortality worldwide. Yet human suicide prediction, prevention and therapeutic systems at this moment are generally ineffective in the clinic. No diagnostic system is reliable for significantly suicidal prevention and mortality reduction. As a result, human suicide etiopathologic investigation (especially at genetic/molecular levels in the clinical settings) is quite necessary. In order to boost human suicide researches, emerging human suicide diagnostic/treatment study will be transformed from clinical symptom observations into new generations of candidate drug targets and therapeutics. To achieve this goal, associations between suicidal etiopathologic identification, genetic/bioinformatics-based diagnostics and putative drug targets must be exploited than ever before. After all, the interaction and relationships between environmental/ genetic/molecular clues and overall patient's risk prediction (environmental influences and different therapeutic targets/types) should be found out. CONCLUSION: In the future, effective clinical suicide prediction, prevention and therapeutic systems can be established via scientific expeditions and causality discovery.

Risperidone-Associated Neuroleptic Malignant Syndrome in an Inpatient With Schizophrenia, With Successful Rechallenge and 3 Year Follow-Up.

Neuroleptic malignant syndrome (NMS) is rare but one of the most serious adverse effects of antipsychotics. Here, we report a case of risperidone-associated NMS in which a successful rechallenge of risperidone was observed with a positive follow-up. A 47-year-old female with schizophrenia was treated with risperidone 4 mg/d for 8 months in 2009 and was admitted to our hospital in 2015 owing to violent behavior under persecutory delusions. Risperidone 2 mg/d was initiated and increased to 4 mg/d 54 days later. Further, long-acting injectable (LAI) risperidone 25 mg per 2 weeks was added on hospital day 15. On hospital day 116, NMS occurred and thus we discontinued all antipsychotics including LAI risperidone, then NMS improved. We resumed LAI risperidone 25 mg per 2 weeks on hospital day 148, thus we waited for 22 days before re-starting the drug treatment. She was discharged on hospital day 371, then switched to LAI paliperidone 150 mg per 4 weeks 2 months later. At the time of a follow-up 3 years later, NMS had not reoccurred. This case reports on an unusual presentation of NMS in which no hyperthermia was observed. Furthermore, this case indicated that NMS may occur in a dose-dependent manner. In conclusion, this case reported important information for clinicians with regard to antipsychotic drug rechallenges and proper dosing of APs to avoid or reverse NMS.