Biomechanical comparison of the therapeutic effect of a novel proximal femoral bionic intramedullary nail and traditional inverted triangle hollow screw on femoral neck fracture.

OBJECTIVE: A novel Proximal Femoral Bionic Nail (PFBN) has been developed by a research team for the treatment of femoral neck fractures. This study aims to compare the biomechanical properties of the innovative PFBN with those of the conventional Inverted Triangular Cannulated Screw (ITCS) fixation method through biomechanical testing. METHODS: Sixteen male femoral specimens preserved in formalin were selected, with the donors' age at death averaging 56.1 ± 6.3 years (range 47-64 years), and a mean age of 51.4 years. The femurs showed no visible damage and were examined by X-rays to exclude diseases affecting bone quality such as tumors, severe osteoporosis, and deformities. The 16 femoral specimens were randomly divided into an experimental group (n = 8) and a control group (n = 8). All femurs were prepared with Pauwels type III femoral neck fractures, fixed with PFBN in the experimental group and ITCS in the control group. Displacement and stress limits of each specimen were measured through cyclic compression tests and failure experiments, and vertical displacement and strain values under a 600 N vertical load were measured in all specimens through vertical compression tests. RESULTS: In the vertical compression test, the average displacement at the anterior head region of the femur was 0.362 mm for the PFBN group, significantly less than the 0.480 mm for the ITCS group (p < 0.001). At the fracture line area, the average displacement for the PFBN group was also lower than that of the ITCS group (0.196 mm vs. 0.324 mm, p < 0.001). The difference in displacement in the shaft area was smaller, but the average displacement for the PFBN group (0.049 mm) was still significantly less than that for the ITCS group (0.062 mm, p = 0.016). The situation was similar on the posterior side of the femur. The average displacements in the head area, fracture line area, and shaft area for the PFBN group were 0.300 mm, 0.168 mm, and 0.081 mm, respectively, while those for the ITCS group were 0.558 mm, 0.274 mm, and 0.041 mm, with significant differences in all areas (p < 0.001). The average strain in the anterior head area for the PFBN group was 4947 µm/m, significantly less than the 1540 µm/m for the ITCS group (p < 0.001). Likewise, in the fracture line and shaft areas, the average strains for the PFBN group were significantly less than those for the ITCS group (p < 0.05). In the posterior head area, the average strain for the PFBN group was 4861 µm/m, significantly less than the 1442 µm/m for the ITCS group (p < 0.001). The strain conditions in the fracture line and shaft areas also showed the PFBN group was superior to the ITCS group (p < 0.001). In cyclic loading experiments, the PFBN fixation showed smaller maximum displacement (1.269 mm vs. 1.808 mm, p < 0.001), indicating better stability. In the failure experiments, the maximum failure load that the PFBN-fixated fracture block could withstand was significantly higher than that for the ITCS fixation (1817 N vs. 1116 N, p < 0.001). CONCLUSION: The PFBN can meet the biomechanical requirements for internal fixation of femoral neck fractures. PFBN is superior in biomechanical stability compared to ITCS, particularly showing less displacement and higher failure resistance in cyclic load and failure experiments. While there are differences in strain performance in different regions between the two fixation methods, overall, PFBN provides superior stability.

Mycn ameliorates cardiac hypertrophy-induced heart failure in mice by mediating the USP2/JUP/Akt/ß-catenin cascade.

BACKGROUND: Pathological cardiac hypertrophy is associated with cardiac dysfunction and is a key risk factor for heart failure and even sudden death. This study investigates the function of Mycn in cardiac hypertrophy and explores the interacting molecules. METHODS: A mouse model of cardiac hypertrophy was induced by isoproterenol (ISO). The cardiac dysfunction was assessed by the heart weight-to-body weight ratio (HW/BW), echocardiography assessment, pathological staining, biomarker detection, and cell apoptosis. Transcriptome alteration in cardiac hypertrophy was analyzed by bioinformatics analysis. Gain- or loss-of-function studies of MYCN proto-oncogene (Mycn), ubiquitin specific peptidase 2 (USP2), and junction plakoglobin (JUP) were performed. The biological functions of Mycn were further examined in ISO-treated cardiomyocytes. The molecular interactions were verified by luciferase assay or immunoprecipitation assays. RESULTS: Mycn was poorly expressed in ISO-treated mice, and its upregulation reduced HW/BW, cell surface area, oxidative stress, and inflammation while improving cardiac function of mice. It also reduced apoptosis of cardiomyocytes in mice and those in vitro induced by ISO. Mycn bound to the USP2 promoter to activate its transcription. USP2 overexpression exerted similar myocardial protective functions. It stabilized JUP protein by deubiquitination modification, which blocked the Akt/ß-catenin pathway. Knockdown of JUP restored phosphorylation of Akt and ß-catenin protein level, which negated the protective effects of USP2. CONCLUSION: This study demonstrates that Mycn activates USP2 transcription, which mediates ubiquitination and protein stabilization of JUP, thus inactivating the Akt/ß-catenin axis and alleviating cardiac hypertrophy-induced heart failure.

GM-CSF-mediated inducement of bone marrow MDSCs by TSA and effect on survival of graft in mice.

OBJECTIVE: This study analyzed the effect of HDAC inhibitor, trichostatin A (TSA), in inducing granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated bone marrow (BM) cell differentiation to myeloid-derived suppressor cells (MDSCs) in vitro and in vivo. METHODS: BM cell differentiation to CD11b + GR-1 + MDSCs was achieved by in vitro culture with TSA and GM-CSF, and the collected cells were analyzed by mixed lymphocyte culture to identify suppressive actions against effector T cells. RT-PCR and ELISA were conducted to analyze the CCL5 mRNA and protein levels in TSA + GM-CSF + BM, GR-1 + MDSCs and GR-1 + MDSC + CCL5 groups. The survival of cardiac grafts was compared between groups. RESULTS: TSA was beneficial for the GM-CSF-mediated BM differentiation to CD11b + GR-1 + MDSCs. Adoptive transfer of GR-1 + MDSCs was powerful in suppressing CD4 + CD25-T cell proliferation and the effect was mediated by iNOS and HO-1; it also increased CCL5 gradient concentration between grafts and plasma to recruit Treg to grafts and prolong the survival of the grafts. Survival analysis revealed that the survival of grafts after adoptive transfer of GR-1 + MDSCs could be prolonged. CONCLUSION: This study helps in further research on the application value of MDSCs in the field of transplant, and may provide a new thought for the cell therapy in inducing immune tolerance in organ transplant.

Laparoscopy vs. Laparotomy for the Management of Abdominal Trauma: A Systematic Review and Meta-Analysis.

Background: There is still no consensus regarding the role of laparoscopy in trauma cases. The purpose of this paper is to assess the value of diagnostic and therapeutic laparoscopy for patients with blunt or penetrating abdominal trauma by performing a systematic review and meta-analysis. Methods: PubMed, Embase, and the Cochrane library were systemically searched for the randomized controlled trials (RCTs) and non-RCT comparative studies on effectiveness and safety of laparoscopy vs. laparotomy for the two authors independently performed the search, data extraction, and quality assessment. Results: A total of 5,517 patients were enrolled in 23 eligible studies that were published in English. Meta-analysis results suggest that there is no significant difference in the incidence of missed injury and mortality between abdominal trauma patients receiving laparoscopy and those receiving laparotomy. Concerning postoperative complications, compared with patients in the open surgery group, those in the laparoscopy group are at a similar risk of intra-abdominal abscesses, thromboembolism, and ileus, while there is a decreased incidence of wound infection and pneumonia. Besides, patients in the laparoscopy group experience shorter hospitalization times and procedure times. For most outcomes, the sensitivity analysis yielded similar results to the primary analysis. Conclusion: Laparoscopic surgery is a practical alternative to laparotomy for appropriate patients. The decision to perform laparoscopy should be based on the experience of the surgeon and the resources available.

Intelligent immune clonal optimization algorithm for pulmonary nodule classification.

Computer-aided diagnosis (CAD) of pulmonary nodules is an effective approach for early detection of lung cancers, and pulmonary nodule classification is one of the key issues in the CAD system. However, CAD has the problems of low accuracy and high false-positive rate (FPR) on pulmonary nodule classification. To solve these problems, a novel method using intelligent immune clonal selection and classification algorithm is proposed and developed in this work. First, according to the mechanism and characteristics of chaotic motion with a logistic mapping, the proposed method utilizes the characteristics of chaotic motion and selects the control factor of the optimal chaotic state, to generate an initial population with randomness and ergodicity. The singleness problem of the initial population of the immune algorithm was solved by the proposed method. Second, considering on the characteristics of Gaussian mutation operator (GMO) with a small scale, and Cauchy mutation operator (CMO) with a big scale, an intelligent mutation strategy is developed, and a novel control factor of the mutation is designed. Therefore, a Gauss-Cauchy hybrid mutation operator is designed. Ultimately, in this study, the intelligent immune clonal optimization algorithm is proposed and developed for pulmonary nodule classification. To verify its accuracy, the proposed method was used to analyze 90 CT scans with 652 nodules. The experimental results revealed that the proposed method had an accuracy of 97.87% and produced 1.52 false positives per scan (FPs/scan), indicating that the proposed method has high accuracy and low FPR.

Effects of off-pump coronary artery bypass graft on the clinical efficacy, surgical indicators, and cardiac function of patients with coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is a common clinical cardiovascular disease. This study aimed to analyze the effects of off-pump coronary artery bypass graft on the clinical efficacy, surgical indicators, and cardiac function of patients with CHD. METHODS: We retrospectively analyzed the clinical data of 120 patients with CHD who were treated in our hospital from May 2017 to May 2020. And they were divided into the control group (extracorporeal coronary artery bypass graft) and the observation group (off-pump coronary artery bypass graft). The clinical efficacy, surgical indicators, cardiac function, myocardial injury, the degree of cardiac autonomic nerve imbalance, incidence of complications and quality of life one year after the operation in the 2 groups were compared. RESULTS: The total effective rate of the observation group was significantly higher than that of the control group. Intraoperative blood loss, operation time, intraoperative blood transfusion, and hospital stay in the observation group were significantly better than those in the control group. After treatment, the levels of cardiac index (CI), ejection fraction (EF), stroke volume (SV), and cardiac output (CO) in the observation group and the control group were higher than those before treatment, especially in the observation group. Compared with those before operation, CK-MB and cTnI of the two groups significantly increased at all time points after surgery. After treatment, SDNN, LF, HF, and TP of patients in the two groups increased, which was significant in the observation group. The incidence of complications such as myocardial infarction, ischemic changes, respiratory insufficiency, and intraoperative ventricular fibrillation in the observation group was significantly lower than that in the control group. The score of quality of life in the observation group was significantly higher than the control group. CONCLUSIONS: In the treatment of patients with CHD, off-pump coronary artery bypass graft has good clinical effects, which can significantly improve the heart function, and cardiac autonomic nerve imbalance of patients, reduce myocardial damage, decrease the incidence of complications, and improve the quality of life. Therefore, off-pump coronary artery bypass graft is worthy of clinical application.

Hessian-MRLoG: Hessian information and multi-scale reverse LoG filter for pulmonary nodule detection.

Computer-aided detection (CADe) of pulmonary nodules is an effective approach for early detection of lung cancer. However, due to the low contrast of lung computed tomography (CT) images, the interference of blood vessels and classifications, CADe has the problems of low detection rate and high false-positive rate (FPR). To solve these problems, a novel method using Hessian information and multi-scale reverse Laplacian of Gaussian (LoG) (Hessian-MRLoG) is proposed and developed in this work. Also, since the intensity distribution of the LoG operator and the lung nodule in CT images are inconsistent, and their shapes are mismatched, a multi-scale reverse Laplacian of Gaussian (MRLoG) is constructed. In addition, in order to enhance the effectiveness of target detection, the second-order partial derivatives of MRLoG are partially adjusted by introducing an adjustment factor. On this basis, the Hessian-MRLoG model is developed, and a novel elliptic filter is designed. Ultimately, in this study, the method of Hessian-MRLoG filtering is proposed and developed for pulmonary nodule detection. To verify its effectiveness and accuracy, the proposed method was used to analyze the LUNA16 dataset. The experimental results revealed that the proposed method had an accuracy of 93.6% and produced 1.0 false positives per scan (FPs/scan), indicating that the proposed method can improve the detection rate and significantly reduce the FPR. Therefore, the proposed method has the potential for application in the detection, localization and labeling of other lesion areas.

HTR2A promotes the development of cardiac hypertrophy by activating PI3K-PDK1-AKT-mTOR signaling.

5-Hydroxytryptamine receptor 2A (HTR2A) is a central regulator of fetal brain development and cognitive function in adults. However, the roles of HTR2A in the cardiovascular system are not fully understood. Here in this study, we explored the function of HTR2A in cardiac hypertrophy. Significantly, the expression levels of HTR2A mRNA and protein levels were upregulated in hypertrophic hearts of human patients. Besides, the expression of HTR2A was also upregulated in isoproterenol (ISO)-induced cardiac hypertrophy in the mouse. Next, the expression of HTR2A was knocked down with shRNA or overexpressed with adenovirus in neonatal rat cardiomyocytes, and ISO was used to induce cardiomyocyte hypertrophy. We showed that HTR2A knockdown repressed ISO-induced cardiomyocyte hypertrophy, which was demonstrated by decreased cardiomyocyte size and repressed expression of hypertrophic fetal genes (e.g., myosin heavy chain beta (ß-Mhc), atrial natriuretic peptide (Anp), and brain natriuretic peptide (Bnp)). By contrast, HTR2A overexpression promoted cardiomyocyte hypertrophy. Of note, we observed that HTR2A promoted the activation (phosphorylation) of AKT-mTOR (mammalian target of rapamycin) signaling in cardiomyocytes, and repression of AKT-mTOR with perifosine or rapamycin blocked the effects of HTR2A on cardiomyocyte hypertrophy. Finally, we showed that HTR2A regulated AKT-mTOR signaling through activating the PI3K-PDK1 pathway, and inhibition of either PI3K or PDK1 blocked the roles of HTR2A in regulating AKT-mTOR signaling and cardiomyocyte hypertrophy. Altogether, these findings demonstrated that HTR2A activated PI3K-PDK1-AKT-mTOR signaling and promoted cardiac hypertrophy.

FBXW7 promotes pathological cardiac hypertrophy by targeting EZH2-SIX1 signaling.

F-box and WD repeat domain-containing 7 (FBXW7) is an E3-ubiquitin ligase, which serves as one of the components of the SKP1, CUL1, and F-box protein type ubiquitin ligase (SCF) complex. Previous studies reveal that FBXW7 participates in cancer, inflammation and Parkinson's disease. FBXW7 also contributes to angiogenesis of endothelial cells. However, the function of FBXW7 in cardiac homeostasis remains to elucidate. Here we identified the critical role of FBXW7 during cardiac hypertrophy in humans and rodents. Quantitative real-time PCR (qRT-PCR) and Western blot revealed that the mRNA and protein levels of FBXW7 were upregulated significantly in hypertrophic hearts in human and mouse as well as Angiotensin II (Ang II)-induced hypertrophic neonatal rat cardiomyocytes (NRCM). Gain-of-function (adenovirus) and loss-of-function (siRNA) experiments provided evidence that FBXW7 promoted Ang II-induced cardiomyocyte hypertrophy as demonstrated by the increase in the size of cardiomyocytes and overexpression of hypertrophic fetal genes myosin heavy chain 7 (Myh7) natriuretic peptide a (Nppa), brain natriuretic peptide (Nppb). Further mechanism study revealed that FBXW7 promoted the expression of sine oculis homeobox homolog 1 (SIX1) in cardiomyocytes, which relied on regulation of the stability of the histone methyltransferase EZH2 (Enhancer of zeste homolog 2). Previous work revealed the pro-hypertrophic role of the EZH2-SIX1 axis in rodents. Indeed, our genetic and pharmacological evidence showed that the EZH2-SIX1 signaling was critically involved in FBXW7 functions in Ang II-induced cardiomyocyte hypertrophy. Therefore, we identified FBWX7 as an important regulator of cardiac hypertrophy via modulating the EZH2-SIX1 axis.

Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling.

Carboxypeptidase A4 (CPA4) is a member of the metallocarboxypeptidase family. Current studies have identified the roles of CPA4 in cancer biology and insulin sensitivity. However, the roles of CPA4 in other diseases are not known. In the present study, we investigated the roles of CPA4 in cardiac hypertrophy. The expression of CPA4 was significantly increased in the hypertrophic heart tissues of human patients and isoproterenol (ISO)-induced hypertrophic heart tissues of mice. We next knocked down Cpa4 with shRNA or overexpressed Cpa4 using adenovirus in neonatal rat cardiomyocytes and induced cardiomyocyte hypertrophy with ISO. We observed that Cpa4 overexpression promoted whereas Cpa4 knockdown reduced ISO-induced growth of cardiomyocyte size and overexpression of hypertrophy marker genes, such as myosin heavy chain ß (ß-Mhc), atrial natriuretic peptide (Anp), and brain natriuretic peptide (Bnp). Our further mechanism study revealed that the mammalian target of rapamycin (mTOR) signaling was activated by Cpa4 in cardiomyocytes, which depended on the phosphoinositide 3-kinase (PI3K)-AKT signaling. Besides, we showed that the PI3K-AKT-mTOR signaling was critically involved in the roles of Cpa4 during cardiomyocyte hypertrophy. Collectively, these results demonstrated that CPA4 is a regulator of cardiac hypertrophy by activating the PI3K-AKT-mTOR signaling, and CPA4 may serve as a promising target for the treatment of hypertrophic cardiac diseases.

Effectiveness and Safety of Combination Therapy of Transarterial Chemoembolization and Apatinib for Unresectable Hepatocellular Carcinoma in the Chinese Population: A Meta-Analysis.

BACKGROUND: The combination of transarterial chemoembolization (TACE) and apatinib has been used in the treatment of intermediate or advanced hepatocellular carcinoma (HCC). However, its effectiveness and safety are also argued. METHODS: Eligible studies were collected from a computer search of literatures published from the database establishment to May 2019 in PubMed, Web of Science, EMBASE, Ovid, the Cochrane Library, Wanfang Database, China National Knowledge Infrastructure, and China Biology Medicine Disc. The objective response rate (ORR), the disease control rate (DCR), survival rate (SR), and the incidences of treatment-related adverse effects (AEs) were collected as the relevant outcomes. Data were analyzed through fixed/random effects of meta-analysis models with RevMan 5.3 software. RESULTS: Eight randomized controlled clinical trials comprising 528 patients and 4 cohort studies comprising 226 patients were eventually included. Compared to the control group treated with TACE solely, combination therapy group, in which intermediate or advanced HCC patients were treated with TACE and apatinib, significantly enhanced ORR (relative risk [RR] 2.06, 95% CI 1.63-2.61, p < 0.001), DCR (RR 1.65, 95% CI 1.24-2.20, p < 0.001), and whole SRs of 6-month (RR 1.52, 95% CI 1.08-2.14, p = 0.02), 1-year (RR 1.52, 95% CI 1.25-1.84, p < 0.001), and 2-year (RR 1.84, 95% CI 1.34-2.54, p < 0.001). The incidence of hand foot syndrome, proteinuria, hypertension, and diarrhea was significantly increased in the combination therapy group compared with the control group (p < 0.05), and the incidence of nausea and vomiting, fever, and myelosuppression, respectively, was similar in 2 groups (p > 0.05). CONCLUSIONS: The combination therapy of TACE and apatinib can enhance the clinical effectiveness better than TACE solely in patients with intermediate or advanced HCC, while increase in the AEs is usually tolerable.

Deletion of Nrf2 leads to hepatic insulin resistance via the activation of NF-κB in mice fed a high-fat diet.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Insulin resistance (IR) is important in the development and progression of NAFLD. Nuclear erythroid 2­related factor 2 (Nrf2) has previously been reported to be a novel regulator in NAFLD. The present study determined that Nrf2 knockdown accelerated the onset of obesity and non­alcoholic steatohepatitis (NASH), via the induction of hepatic IR in mice fed a high­fat diet (HFD), which was confirmed by an increase in total and hepatic weight in Nrf2­null­HFD mice, in addition to marked structural disorder in liver tissues from the Nrf2­null­HFD group analyzed by histopathological examination. Subsequently, it was demonstrated that hepatic IR in Nrf2­null­HFD mice was influenced by oxidative stress; this was confirmed by an increase in malondialdehyde levels and a decrease in glutathione levels. In addition, it was determined that the induction of hepatic IR by Nrf2 knockdown in HFD-treated mice was regulated by activation of the nuclear factor­κB (NF­κB) signaling pathway, as detected by an increase in the expression levels of nuclear NF­κB, and its downstream effectors interleukin­6 and tumor necrosis factor­α. The present study provides insight into the function of Nrf2 in NAFLD, indicating that Nrf2 deletion may lead to hepatic IR by activation of NF­κB, which is often associated with oxidative stress. Therefore, activation of Nrf2 may limit disease progression and act as a therapeutic approach for the treatment of NASH.

Antitumor activity of a sulfated polysaccharide from Enteromorpha intestinalis targeted against hepatoma through mitochondrial pathway.

A sulfated polysaccharide (EI-SP), extracted from Enteromorpha intestinalis that is a kind of algae, is found to have anticancer activity. This study was designed to investigate the anti-tumor effect of EI-SP on human hepatoma HepG2 cell line and its possible mechanisms. An MTT assay showed that EI-SP could specifically inhibit the growth of human hepatoma HepG2 cells in a dose-dependent manner. Analysis by flow cytometry indicated that the apoptosis of tumor cells increased after treatment with EI-SP in range of 100-400 µg/ml. Furthermore, Western blot analysis showed that EI-SP treatment led to decreased protein expression of Bcl-2 and an increase in Bax, cleaved caspase-3, cleaved caspase-9 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, it was found that EI-SP caused a loss of mitochondrial membrane potential (Δψ m) and the release of cytochrome c to the cytosol. Collectively, our results showed that the EI-SP induces apoptosis in HepG2 cells involving a caspases-mediated mitochondrial signalling pathway.

HIV reverse transcriptase activity assay: a feasible surrogate for HIV viral load measurement in China.

The quantitation of HIV viral load using an assay that measures the activity of reverse transcriptase (RT) may provide an alternative strategy for the monitoring of HIV viral load within resource-limited areas in China. Plasma viral load analyses of 215 samples from 87 patients infected with HIV were detected using the RT activity assay (ExaVir Load versions 2 and 3; Cavidi, Uppsala, Sweden) and RT polymerase chain reaction (PCR) (COBAS TaqMan 48, Amplink version 3.2; Roche Molecular Systems, Branchburg, NJ). The RT activity assay versions 3 (RT3) and 2 (RT2) could detect 95.3% and 86.9% of samples with measurable RNA by RT-PCR, respectively. A stronger correlation was observed between viral loads detected by RT3 and RT-PCR than between RT2 and RT-PCR (r = 0.95, P < 0.001, and r = 0.92, P < 0.001, respectively). The correlation between serial samples collected from 6 patients at 1, 3, 6, 12, 18, and 24 months after beginning triple combination antiretroviral therapy, using the 2 different methodologies, was also strong (r = 0.99, P < 0.001, for RT3 and RT-PCR, r = 0.98, P < 0.001, for RT2 and RT-PCR). The viral loads detected by RT activity assay were inversely correlated with CD4(+) T-cell counts. Reproducibility of the RT activity assay was assessed by testing 3 samples in triplicate by 3 different operators. Viral load testing using assays that measure HIV RT activity is an affordable, feasible, simple, and reliable alternative for HIV RNA viral load determination in laboratories in China and other developing countries.

Association between HIV Type 1-specific T cell responses and CD4+ T cell counts or CD4+:CD8+ T cell ratios in HIV Type 1 subtype B infection in China.

CD4+ T cell counts and CD4+:CD8+ T cell ratios represent key determinants of HIV disease progression and infectivity. However, the relationship between the HIV-1-specific cytotoxic T lymphocyte (CTL) response and these determinants has not been elucidated for all HIV-1B and HIV-1C proteins. In the present study, virusspecific T cell responses to HIV-1B and HIV-1C proteins were analyzed with interferon gamma (IFN-gamma) enzyme- linked immunospot (ELISpot) assays using synthetic overlapping peptides corresponding to naturally occurring HIV-1B and HIV-1C consensus sequences. For Gag/Gag p24/Gag p17, a correlation between T cell responses and CD4+ T cell count in HIV-1 clade B and clade C was seen: elevated T cell response resulted in higher CD4+ T cell production. A statistically significant correlation between the Pol-specific T cell response and CD4+ T cell counts was also found in HIV-1 subtype C. For all HIV-1B and HIV-1C proteins, a correlation between the HIV-1-specific T cell response and CD4+:CD8+ T cell ratios was found for Tat and Pol proteins. CD4+ T cell counts in patients with Tat and/or Rev T cell response were higher than in patients without Tat and/or Rev T cell response. We suggest that this correlation within HIV-1B and HIV-1C Gag p24/Gag p17 responses makes the Gag p24/Gag p17 region a potential vaccine candidate and that HIV-1-specific CTL epitopes toward Pol are important in controlling HIV-1 infection; we emphasize that future vaccination strategies should include these early antigens, Tat and Rev.