A Novel Multi-Strain E3 Probiotic Formula Improved the Gastrointestinal Symptoms and Quality of Life in Chinese Psoriasis Patients.

Psoriasis is a chronic immune-mediated inflammatory disease affecting the skin and other systems. Gastrointestinal disease was found to be correlated with psoriasis in previous studies and it can significantly affect the quality of life of psoriasis patients. Despite the importance of the gut microbiome in gut and skin health having already been demonstrated in many research studies, the potential effect of probiotics on GI comorbidities in psoriasis patients is unclear. To investigate the effects of probiotics on functional GI comorbidities including irritable bowel syndrome, functional constipation, and functional diarrhea in psoriasis patients, we conducted a targeted 16S rRNA sequencing and comprehensive bioinformatic analysis among southern Chinese patients to compare the gut microbiome profiles of 45 psoriasis patients over an 8-week course of novel oral probiotics. All the participants were stratified into responders and non-responders according to their improvement in GI comorbidities, which were based on their Bristol Stool Form Scale (BSFS) scores after intervention. The Dermatological Life Quality Index (DLQI) score revealed a significant improvement in quality of life within the responder group (DLQI: mean 10.4 at week 0 vs. mean 15.9 at week 8, p = 0.0366). The proportion of psoriasis patients without GI comorbidity manifestation at week 8 was significantly higher than that at week 0 (week 0: Normal 53.33%, Constipation/Diarrhea 46.67%; week 8: Normal 75.56%, Constipation/Diarrhea 24.44%, p = 0.0467). In addition, a significant difference in the gut microbiome composition between the responders and non-responders was observed according to alpha and beta diversities. Differential abundance analysis revealed that the psoriasis patients exhibited (1) an elevated relative abundance of Lactobacillus acidophilus, Parabacteroides distasonis, and Ruminococcus bromii and (2) a reduced relative abundance of Oscillibacter, Bacteroides vulgatus, Escherichia sp., and Biophila wadsworthia after the 8-week intervention. The responders also exhibited a higher relative abundance of Fusicatenibacter saccharivorans when compared to the non-responders. In summary, our study discovers the potential clinical improvement effects of the novel probiotic formula in improving GI comorbidities and quality of life in psoriasis patients. We also revealed the different gut microbiome composition as well as the gut microbial signatures in the patients who responded to probiotics. These findings could provide insight into the use of probiotics in the management of psoriasis symptoms.

CRISPR-Cas12-based nucleic acids detection systems.

Because of the outstanding contribution in genome editing, CRISPR has undoubtedly become the most popular technology around the world and two pioneers are awarded the Nobel Prize in Chemistry this year. Besides, along with the discovery of nonspecific trans-cleavage activities of several Cas proteins such as Cas12 and Cas13, many CRISPR-based molecular diagnostic systems have been successfully created, showing advantages in sensitivity, specificity and operation convenience. Among them, systems with Cas12, which targets DNA and trans-cleaves single-stranded DNA probes, are both simple and highly efficient. Here in this review, we mainly focus on the Cas12-based methods and briefly discuss their applications in nucleic acids detection and beyond.

Rethinking COVID-19 test sensitivity-a strategy for improving the detection limit.

Numerous genetic tests for the detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, including those based on the ever-popular real-time polymerase chain reaction (RT-qPCR) technique, have been reported. These diagnostic tests give false negatives particularly during the early and late stages of COVID-19 clearly indicating inadequate test sensitivity. The entire COVID-19 diagnostic workflow is often overlooked and given very little attention. Herein, we propose that volumetric modifications to COVID-19 workflows would significantly improve detection limits. We would therefore encourage researchers to adopt a holistic approach, in which all the steps of a COVID-19 diagnostic workflow, are carefully scrutinised, particularly those upstream factors at the viral sampling and pre-analytical stages.

Recent Advances in Understandings Towards Pathogenesis and Treatment for Intrauterine Adhesion and Disruptive Insights from Single-Cell Analysis.

Intrauterine adhesion is a major cause of menstrual irregularities, infertility, and recurrent pregnancy losses and the progress towards its amelioration and therapy is slow and unsatisfactory. We aim to summarize and evaluate the current treatment progress and research methods for intrauterine adhesion. We conducted literature review in January 2020 by searching articles at PubMed on prevention and treatment, pathogenesis, the repair of other tissues/organs, cell plasticity, and the stem cell-related therapies for intrauterine adhesion. A total of 110 articles were selected for review. Uterine cell heterogeneity, expression profile, and cell-cell interaction were investigated based on scRNA-seq of uterus provided by Human Cell Landscape (HCL) project. Previous knowledge on intrauterine adhesion (IUA) pathogenesis was mostly derived from correlation studies by differentially expressed genes between endometrial tissue of intrauterine adhesion patients/animal models and normal endometrial tissue. Although the TGF-ß1/SMAD pathway was suggested as the key driver for IUA pathogenesis, uterine cell heterogeneity and distinct expression profile among different cell types highlighted the importance of single-cell investigations. Cell-cell interaction in the uterus revealed the central hub of endothelial cells interacting with other cells, with endothelial cells in endothelial to mesenchymal transition and fibroblasts as the strongest interaction partners. The potential of stem cell-related therapies appeared promising, yet suffers from largely animal studies and nonstandard study design. The need to dissect the roles of endometrial cells, endothelial cells, and fibroblasts and their interaction is evident in order to elucidate the molecular and cellular mechanisms in both intrauterine adhesion pathogenesis and treatment.

Correction to: Involvement of gut microbiome in human health and disease: brief overview, knowledge gaps and research opportunities.

[This corrects the article DOI: 10.1186/s13099-018-0230-4.].

Involvement of gut microbiome in human health and disease: brief overview, knowledge gaps and research opportunities.

The commensal, symbiotic, and pathogenic microbial community which resides inside our body and on our skin (the human microbiome) can perturb host energy metabolism and immunity, and thus significantly influence development of a variety of human diseases. Therefore, the field has attracted unprecedented attention in the last decade. Although a large amount of data has been generated, there are still many unanswered questions and no universal agreements on how microbiome affects human health have been agreed upon. Consequently, this review was written to provide an updated overview of the rapidly expanding field, with a focus on revealing knowledge gaps and research opportunities. Specifically, the review covered animal physiology, optimal microbiome standard, health intervention by manipulating microbiome, knowledge base building by text mining, microbiota community structure and its implications in human diseases and health monitoring by analyzing microbiome in the blood. The review should enhance interest in conducting novel microbiota investigations that will further improve health and therapy.

Insights into intercontinental spread of Zika virus.

The epidemic of Zika virus (ZIKV) infection in South America has led to World Health Organization's declaration of a Public Health Emergency of International Concern. To further inform effective public health policy, an understanding of ZIKV's transmission mechanisms is crucial. To characterize the intercontinental transmission of ZIKV, we compiled and analyzed more than 250 gene sequences together with their sequence-related geographic and temporal information, sampled across 27 countries spanning from 1947 to 2016. After filtering and selecting appropriate sequences, extensive phylogenetic analyses were performed. Although phylogeographic reconstruction supported the transmission route of the virus in Africa, South-eastern Asia, Oceania and Latin America, we discovered that the Eastern Africa origin of ZIKV was disputable. On a molecular level, purifying selection was found to be largely responsible for the evolution of non-structural protein 5 and envelope protein E. Our dataset and ancestral sequences reconstruction analysis captured previously unidentified amino acid changes during evolution. Finally, based on the estimation of the time to the most recent common ancestors for the non-structural protein 5 gene, we hypothesized potential specific historic events that occurred in the 1940s and might have facilitated the spread of Zika virus from Africa to South-eastern Asia. Our findings provide new insights into the transmission characteristics of ZIKV, while further genetic and serologic studies are warranted to support the design of tailored prevention strategies.

Evidence-Based interventions of Norovirus outbreaks in China.

BACKGROUND: In resource-limited settings where laboratory capacity is limited and response strategy is non-specific, delayed or inappropriate intervention against outbreaks of Norovirus (NoV) are common. Here we report interventions of two norovirus outbreaks, which highlight the importance of evidence-based modeling and assessment to identify infection sources and formulate effective response strategies. METHODS: Spatiotemporal scanning, mathematical and random walk modeling predicted the modes of transmission in the two incidents, which were supported by laboratory results and intervention outcomes. RESULTS: Simulation results indicated that contaminated water was 14 to 500 fold more infectious than infected individuals. Asymptomatic individuals were not effective transmitters. School closure for up to a week still could not contain the outbreak unless the duration was extended to 10 or more days. The total attack rates (TARs) for waterborne NoV outbreaks reported in China (n = 3, median = 4.37) were significantly (p < 0.05) lower than worldwide (n = 14, median = 41.34). The low TARs are likely due to the high number of the affected population. CONCLUSIONS: We found that school closure alone could not contain Norovirus outbreaks. Overlooked personal hygiene may serve as a hotbed for infectious disease transmission. Our results reveal that evidence-based investigations can facilitate timely interventions of Norovirus transmission.

Meteorological Factors for Dengue Fever Control and Prevention in South China.

Dengue fever (DF) is endemic in Guangzhou and has been circulating for decades, causing significant economic loss. DF prevention mainly relies on mosquito control and change in lifestyle. However, alert fatigue may partially limit the success of these countermeasures. This study investigated the delayed effect of meteorological factors, as well as the relationships between five climatic variables and the risk for DF by boosted regression trees (BRT) over the period of 2005-2011, to determine the best timing and strategy for adapting such preventive measures. The most important meteorological factor was daily average temperature. We used BRT to investigate the lagged relationship between dengue clinical burden and climatic variables, with the 58 and 62 day lag models attaining the largest area under the curve. The climatic factors presented similar patterns between these two lag models, which can be used as references for DF prevention in the early stage. Our results facilitate the development of the Mosquito Breeding Risk Index for early warning systems. The availability of meteorological data and modeling methods enables the extension of the application to other vector-borne diseases endemic in tropical and subtropical countries.

An optimized protocol for generation and analysis of Ion Proton sequencing reads for RNA-Seq.

BACKGROUND: Previous studies compared running cost, time and other performance measures of popular sequencing platforms. However, comprehensive assessment of library construction and analysis protocols for Proton sequencing platform remains unexplored. Unlike Illumina sequencing platforms, Proton reads are heterogeneous in length and quality. When sequencing data from different platforms are combined, this can result in reads with various read length. Whether the performance of the commonly used software for handling such kind of data is satisfactory is unknown. RESULTS: By using universal human reference RNA as the initial material, RNaseIII and chemical fragmentation methods in library construction showed similar result in gene and junction discovery number and expression level estimated accuracy. In contrast, sequencing quality, read length and the choice of software affected mapping rate to a much larger extent. Unspliced aligner TMAP attained the highest mapping rate (97.27 % to genome, 86.46 % to transcriptome), though 47.83 % of mapped reads were clipped. Long reads could paradoxically reduce mapping in junctions. With reference annotation guide, the mapping rate of TopHat2 significantly increased from 75.79 to 92.09 %, especially for long (>150 bp) reads. Sailfish, a k-mer based gene expression quantifier attained highly consistent results with that of TaqMan array and highest sensitivity. CONCLUSION: We provided for the first time, the reference statistics of library preparation methods, gene detection and quantification and junction discovery for RNA-Seq by the Ion Proton platform. Chemical fragmentation performed equally well with the enzyme-based one. The optimal Ion Proton sequencing options and analysis software have been evaluated.

Association of immune recovery with hyperlipidaemia and apolipoprotein gene polymorphisms following highly active antiretroviral therapy in a cohort of Chinese HIV patients.

OBJECTIVE: To examine the associations between CD4 recovery, dyslipidaemia and apolipoprotein (APO) gene single nucleotide polymorphisms (SNPs) following highly active antiretroviral therapy (HAART). DESIGN: Retrospective observational cohort study. SETTING: A major HIV care clinic in Hong Kong. PARTICIPANTS: 197 Chinese treatment-naïve HIV patients. OUTCOME MEASURES: Maximum CD4 count and its rise 2-3 years after HAART initiation and their association with abnormal total cholesterol (TC), triglyceride (TG) and 8 selected APO SNP at multiple time points. RESULTS: Before HAART, abnormal levels of TC, TG, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were detected in 13%, 26%, 59% and 19% of the recruited patients, respectively. APOA5 -1131T>C and c.553G>T were significantly associated with high pre-HAART TG while APOE 2198C>T was correlated with high TG at baseline and/or a rise 2-3 years following HAART initiation. Poor CD4 achievement, defined as the highest CD4 count <350/µL and a net gain of <100/µL, was associated with a low CD4 count ≤200/µL at baseline and a rise of TC beyond 5.17 mmol/L following HAART with or without the use of antilipid agents. Conversely, satisfactory CD4 achievement was associated with APOC3 3238GG genotype. Applying a linear generalised estimating equation, APOA5 -1131T>C was shown to be a predictor of a weaker temporal trend for CD4 response in the presence of a low baseline CD4≤200/µL. CONCLUSIONS: Dyslipidaemia plays a predictive role in impacting immunological recovery following HAART, which could be partly explained by the APO gene SNP.

Phylogenetic and Structural Significance of Dihydrofolate Synthase (folC) Mutations in Drug-Resistant Mycobacterium tuberculosis.

The aim of this study is to investigate the mutation pattern of the folC gene in drug-resistant Mycobacterium tuberculosis (MTB) clinical isolates of global and Hong Kong cohorts. The public sequence read archives of 1,124 MTB genomes from three independent studies were retrieved and folC mutations existing solely in drug-resistant MTB strains were identified. A phylogenetic tree was constructed to analyze the segregation of mutation-related amino acid residues in the FolC structure. These mutation sites were further supported by direct Sanger sequencing of the folC gene among 254 clinical MTB isolates in a Hong Kong cohort. Homology modeling of wild-type and mutated FolC was performed, and the predicted structures were docked with hydroxydihydropteroate, the metabolic derivative of para-aminosalicylic acid (PAS), to evaluate the resultant binding affinity changes. Combining the results of three previous cohorts and our cohort, E40, I43, S150, and E153 are the most frequently affected amino acid residues in resistant isolates. Based on the distribution of mutations in the genome-based phylogenetic tree, lineage-specific mutation patterns were observed. Regarding the segregation of affected amino acid residues, the four most frequently affected residues are all in close proximity of the binding pocket for the PAS derivative. Molecular modeling results showed that mutations at E40, I43, and S150 can alter the structure of FolC putative binding pocket, causing the PAS derivative to bind outside of the now deformed pocket. This might ablate the interaction between the protein and the PAS derivative. To conclude, this study is the first comprehensive mutation pattern and bioinformatics analysis of the folC gene in MTB drug-resistant isolates. The distribution of mutations in phylogenetic lineages and protein structure is reported, analyzed, and discussed.

Genome-guided Investigation of Antibiotic Substances produced by Allosalinactinospora lopnorensis CA15-2(T) from Lop Nor region, China.

Microbial secondary metabolites are valuable resources for novel drug discovery. In particular, actinomycetes expressed a range of antibiotics against a spectrum of bacteria. In genus level, strain Allosalinactinospora lopnorensis CA15-2(T) is the first new actinomycete isolated from the Lop Nor region, China. Antimicrobial assays revealed that the strain could inhibit the growth of certain types of bacteria, including Acinetobacter baumannii and Staphylococcus aureus, highlighting its clinical significance. Here we report the 5,894,259 base pairs genome of the strain, containing 5,662 predicted genes, and 832 of them cannot be detected by sequence similarity-based methods, suggesting the new species may carry a novel gene pool. Furthermore, our genome-mining investigation reveals that A. lopnorensis CA15-2(T) contains 17 gene clusters coding for known or novel secondary metabolites. Meanwhile, at least six secondary metabolites were disclosed from ethyl acetate (EA) extract of the fermentation broth of the strain by high-resolution UPLC-MS. Compared with reported clusters of other species, many new genes were found in clusters, and the physical chromosomal location and order of genes in the clusters are distinct. This study presents evidence in support of A. lopnorensis CA15-2(T) as a potent natural products source for drug discovery.

Circulating microbial RNA and health.

Measurement of health indicators in the blood is a commonly performed diagnostic procedure. Two blood studies one involving extended observations on the health of an individual by integrative Personal Omics Profiling (iPOP), and the other tracking the impact of Left Ventricular Assist Device (LVAD) placement on nine heart failure patients were examined for the association of change in health status with change in microbial RNA species. Decrease in RNA expression ratios of human to bacteria and viruses accompanying deteriorated conditions was evident in both studies. Despite large between-subject variations in bacterial composition before LVAD implantation among all the patients, on day 180 after the implantation they manifested apparent between-subject bacterial similarity. In the iPOP study three periods, namely, pre-respiratory syncytial virus (RSV) infection with normal blood glucose level, RSV infection with normal blood glucose level, and post-RSV infection with high blood glucose level could be defined. The upsurge of Enterobacteria phage PhiX 174 sensu lato and Escherichia coli gene expression, in which membrane transporters, membrane receptors for environment signalling, carbohydrate catabolic genes and carbohydrate-active enzymes were enriched only throughout the second period, which suggests a potentially overlooked microbial response to or modulation of the host blood glucose level.

Virtual Pharmacist: A Platform for Pharmacogenomics.

We present Virtual Pharmacist, a web-based platform that takes common types of high-throughput data, namely microarray SNP genotyping data, FASTQ and Variant Call Format (VCF) files as inputs, and reports potential drug responses in terms of efficacy, dosage and toxicity at one glance. Batch submission facilitates multivariate analysis or data mining of targeted groups. Individual analysis consists of a report that is readily comprehensible to patients and practioners who have basic knowledge in pharmacology, a table that summarizes variants and potential affected drug response according to the US Food and Drug Administration pharmacogenomic biomarker labeled drug list and PharmGKB, and visualization of a gene-drug-target network. Group analysis provides the distribution of the variants and potential affected drug response of a target group, a sample-gene variant count table, and a sample-drug count table. Our analysis of genomes from the 1000 Genome Project underlines the potentially differential drug responses among different human populations. Even within the same population, the findings from Watson's genome highlight the importance of personalized medicine. Virtual Pharmacist can be accessed freely at http://www.sustc-genome.org.cn/vp or installed as a local web server. The codes and documentation are available at the GitHub repository (https://github.com/VirtualPharmacist/vp). Administrators can download the source codes to customize access settings for further development.

The Effectiveness of Age-Specific Isolation Policies on Epidemics of Influenza A (H1N1) in a Large City in Central South China.

During the early stage of a pandemic, isolation is the most effective means of controlling transmission. However, the effectiveness of age-specific isolation policies is not clear; especially little information is available concerning their effectiveness in China. Epidemiological and serological survey data in the city of Changsha were employed to estimate key model parameters. The average infectious period (date of recovery-date of symptom onset) of influenza A (H1N1) was 5.2 days. Of all infected persons, 45.93% were asymptomatic. The basic reproduction number of the influenza A (H1N1) pandemic was 1.82. Based on the natural history of influenza A (H1N1), we built an extended susceptible-exposed-infectious/asymptomatic-removed model, taking age groups: 0-5, 6-14, 15-24, 25-59, and ≥60 years into consideration for isolation. Without interventions, the total attack rates (TARs) in each age group were 42.73%, 41.95%, 20.51%, 45.03%, and 37.49%, respectively. Although the isolation of 25-59 years-old persons was the most effective, the TAR of individuals of aged 0-5 and 6-14 could not be reduced. Paradoxically, isolating individuals ≥60 year olds was not predicted to be an effective way of reducing the TAR in this group but isolating the age-group 25-59 did, which implies inter-age-group transmission from the latter to the former is significant. Isolating multiple age groups increased effectiveness. The most effective combined isolation target groups were of 6-14 + 25-59 year olds, 6-14 + 15-24 + 25-59 year olds, and 0-5 + 6-14 + 25-59 + ≥60 year olds. The last of these isolation schemas reduced the TAR of the total population from 39.64% to 0.006%, which was exceptionally close to the effectiveness of isolating all five age groups (TAR = 0.004%).

The draft genome, transcriptome, and microbiome of Dermatophagoides farinae reveal a broad spectrum of dust mite allergens.

BACKGROUND: A sequenced house dust mite (HDM) genome would advance our understanding of HDM allergens, a common cause of human allergies. OBJECTIVE: We sought to produce an annotated Dermatophagoides farinae draft genome and develop a combined genomic-transcriptomic-proteomic approach for elucidation of HDM allergens. METHODS: A D farinae draft genome and transcriptome were assembled with high-throughput sequencing, accommodating microbiome sequences. The allergen gene structures were validated by means of Sanger sequencing. The mite's microbiome composition was determined, and the predominant genus was validated immunohistochemically. The allergenicity of a ubiquinol-cytochrome c reductase binding protein homologue was evaluated with immunoblotting, immunosorbent assays, and skin prick tests. RESULTS: The full gene structures of 20 canonical allergens and 7 noncanonical allergen homologues were produced. A novel major allergen, ubiquinol-cytochrome c reductase binding protein-like protein, was found and designated Der f 24. All 40 sera samples from patients with mite allergy had IgE antibodies against rDer f 24. Of 10 patients tested, 5 had positive skin reactions. The predominant bacterial genus among 100 identified species was Enterobacter (63.4%). An intron was found in the 13.8-kDa D farinae bacteriolytic enzyme gene, indicating that it is of HDM origin. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed a phototransduction pathway in D farinae, as well as thiamine and amino acid synthesis pathways, which is suggestive of an endosymbiotic relationship between D farinae and its microbiome. CONCLUSION: An HDM genome draft produced from genomic, transcriptomic, and proteomic experiments revealed allergen genes and a diverse endosymbiotic microbiome, providing a tool for further identification and characterization of HDM allergens and development of diagnostics and immunotherapeutic vaccines.

Investigation of key interventions for shigellosis outbreak control in China.

Shigellosis is a major public health concern in China, where waterborne disease outbreaks are common. Shigellosis-containing strategies, mostly single or multiple interventions, are implemented by primary-level health departments. Systematic assessment of the effectiveness of these measures is scarce. To estimate the efficacy of commonly used intervention strategies, we developed a Susceptible-Exposed-Infectious/Asymptomatic-Recovered-Water model. No intervention was predicted to result in a total attack rate (TAR) of 90% of the affected population (95% confidence interval [CI]: 86.65-92.80) and duration of outbreak (DO) of 89 days, and the use of single-intervention strategies can be futile or even counter-productive. Prophylactics and water disinfection did not improve TAR or DO. School closure for up to 3 weeks did not help but only increased DO. Isolation alone significantly increased DO. Only antibiotics treatment could shorten the DO to 35 days with TAR unaffected. We observed that these intervention effects were additive when in combined usage under most circumstances. Combined intervention "Isolation+antibiotics+prophylactics+water disinfection" was predicted to result in the lowest TAR (41.9%, 95%CI: 36.97-47.04%) and shortest DO (28 days). Our actual Shigellosis control implementation that also included school closure for 1 week, attained comparable results and the modeling produced an epidemic curve of Shigellosis highly similar to our actual outbreak data. This lends a strong support to the reality of our model that provides a possible reference for public health professionals to evaluate their strategies towards Shigellosis control.

Quick, sensitive and specific detection and evaluation of quantification of minor variants by high-throughput sequencing.

Minor variants have significant implications in quasispecies evolution, early cancer detection and non-invasive fetal genotyping but their accurate detection by next-generation sequencing (NGS) is hampered by sequencing errors. We generated sequencing data from mixtures at predetermined ratios in order to provide insight into sequencing errors and variations that can arise for which simulation cannot be performed. The information also enables better parameterization in depth of coverage, read quality and heterogeneity, library preparation techniques, technical repeatability for mathematical modeling, theory development and simulation experimental design. We devised minor variant authentication rules that achieved 100% accuracy in both testing and validation experiments. The rules are free from tedious inspection of alignment accuracy, sequencing read quality or errors introduced by homopolymers. The authentication processes only require minor variants to: (1) have minimum depth of coverage larger than 30; (2) be reported by (a) four or more variant callers, or (b) DiBayes or LoFreq, plus SNVer (or BWA when no results are returned by SNVer), and with the interassay coefficient of variation (CV) no larger than 0.1. Quantification accuracy undermined by sequencing errors could neither be overcome by ultra-deep sequencing, nor recruiting more variant callers to reach a consensus, such that consistent underestimation and overestimation (i.e. low CV) were observed. To accommodate stochastic error and adjust the observed ratio within a specified accuracy, we presented a proof of concept for the use of a double calibration curve for quantification, which provides an important reference towards potential industrial-scale fabrication of calibrants for NGS.

The Association between Yang-Deficient Constitution and Clinical Outcome of Highly Active Antiretroviral Therapy on People Living with HIV.

Objective. To determine the association between Yang-Deficient Constitution and the clinical outcomes of HIV/AIDS patients who have initiated highly active antiretroviral therapy (HAART). Method. A total of 197 antiretroviral-naive adults who initiated HAART between 2009 and 2011 were recruited. The participants were asked to complete a questionnaire twice to assess their Yang-Deficient Constitution status before HAART. During the study, signs and symptoms and CD4 or CD8 T cell counts were recorded. Routine blood and biochemical tests were conducted. For the patients who were found to have infections, pathologic examination was performed. Statistical test of association of clinical attributes and demographic factors with Yang-Deficient Constitution was conducted. Result. Good test-retest reliability was observed for Yang-Deficient Constitution scoring. The median Yang-Deficient Constitution score of 142 eligible participants was 25. Female (score = 32.14, P < 0.05), hepatotoxicity (32.14, P < 0.1), nephrotoxicity (37.50, P < 0.1), total number of adverse events (P < 0.1), and mortality (39.29, P < 0.05) were associated with Yang-Deficient Consitution, while annual changes or nadir values of CD4 or CD8 T lymphocytes, and newly acquired infections after starting HAART were not. Mortality was also associated with total number of adverse events (P < 0.05), hepatotoxicity (P < 0.05), and nephrotoxicity (P < 0.05). Conclusion. Yang-Deficient Constitution score has a potential to be developed as a predictor for early HIV-related mortality and side effects. The interrelation and underlying mechanisms should be further investigated for evidence-based design of a more appropriate treatment strategy.