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Objective This study aims to investigate the mortality among HIV/AIDS patients receiving antiretroviral therapy (ART) in Fangchenggang City, Guangxi Province, and to identify associated factors with AIDS-related and non-AIDS-related deaths, providing scientific evidence for reducing AIDS mortality. Methods We collected data from the National Comprehensive AIDS Prevention and Control Information System. These data included socio-demographic and follow-up records of 2 728 HIV-1 infected individuals receiving Antiretroviral Therapy (ART) treatment in Fangchenggang City from January 1, 2005 to July 5, 2022. This dataset included socio-demographic and follow-up records during the specified period, providing a comprehensive insight into the therapeutic responses, survival rates, and potential associated complications among ART-treated HIV/AIDS patients within Fangchenggang City. Socio-demographic and follow-up data were analyzed using the cumulative incidence function (CIF) under a competing risk framework and the Fine-Gray subdistribution hazard regression model to assess the associated factors with both AIDS-related and non-AIDS-related deaths. Results With an average follow-up period of 6.7 person-years, 295 cases experienced AIDS-related death with a mortality rate of 1.06/100 person-years, while 227 cases died from non-AIDS-related causes, with a mortality rate of 1.2/100 person-years. Under consideration of competing risks, the cumulative incidence of AIDS-related death at 1 year, 5 years, and 13 years post-diagnosis was 2.5%, 8.5%, and 15.0%, respectively. The factors associated with a higher risk of AIDS-related death included: age 60 years or older (aHR = 1.5, 95% CI: 1.05~2.15), current spouse's infection status unknown/not investigated (aHR = 1.39, 95 % CI: 1.03~1.90), history of prophylactic treatment for opportunistic infections (aHR = 1.4, 95% CI: 1.06~1.84), and occurrence of opportunistic infections or tumors (aHR = 1.65, 95% CI: 1.12~2.45) . On the contrary, factors associated with a lower risk of AIDS-related death included: being female (aHR = 0.61, 95% CI: 0.49~0.90), initial treatment regimen containing EFV (aHR = 0.41, 95% CI: 0.25~0.68), having changed the treatment regimen (aHR = 0.19, 95% CI: 0.12~0.29), first CD4 cell count ≥ 200 cells/µL (aHR = 0.30, 95% CI: 0.20~0.45), initial viral load (VL) between 50 to 1000 copies/ml (aHR = 0.31, 95% CI: 0.18-0.54), and VL < 50 copies/ml (aHR = 0.61, 95% CI: 0.44~0.84). Regarding non-AIDS related deaths, passive detection (aHR = 1.41, 95% CI: 1.0~1.98), uninvestigated/unknown spouse's infection status (aHR = 1.40, 95% CI: 1.01~1.95), and first CD4 cell count ≥200 cells/ (JLL (aHR = 1.68, 95% CI: 1.27~2.22) were found to be associated with increased risk. In contrast, lower risk factors included being female (aHR = 0.55, 95 % CI: 0.37-0.81), having experienced a change in antiviral treatment regimen post-initiation (aHR = 0.33, 95%CI :0.21-0.50), initial treatment regimens containing EFV (aHR = 0.55, 95% CI: 0.34-0.88), and NVP (aHR = 0.50, 95% CI: 0.3-0.83). Conclusion The mortality rate among HIV/AIDS patients receiving ART in Fangchenggang City is relatively low. This study underscores the importance of preventing and treating opportunistic infections or tumors for improving the survival of HIV/AIDS patients. HIV/AIDS care clinics should particularly focus on monitoring and following up on female patients, older patients, and those detected passively, enhancing medication adherence, expanding HIV testing among key populations, and thereby striving to reduce the mortality rate among AIDS patients. [ABSTRACT FROM AUTHOR]

Background The study purpose was to characterize the mycobiome and its associations with the expression of pathogenic genes in esophageal squamous cell carcinoma (ESCC). Methods Patients with primary ESCC were recruited from two central hospitals. We performed internal transcribed spacer 1 (ITS1) ribosomal DNA sequencing analysis. We compared differential fungi and explored the ecology of fungi and the interaction of bacteria and fungi. Results The mycobiota diversity was significantly different between tumors and tumor-adjacent samples. We further analysed the differences between the two groups, at the species level, confirming that Rhodotorula toruloides , Malassezia dermatis , Hanseniaspora lachancei , and Spegazzinia tessarthra were excessively colonized in the tumor samples, whereas Preussia persica , Fusarium solani , Nigrospora oryzae , Acremonium furcatum , Golovinomyces artemisiae , and Tausonia pullulans were significantly more abundant in tumor-adjacent samples. The fungal co-occurrence network in tumor-adjacent samples was larger and denser than that in tumors. Similarly, the more complex bacterial–fungal interactions in tumor-adjacent samples were also detected. The expression of mechanistic target of rapamycin kinase was positively correlated with the abundance of N. oryzae and T. pullulans in tumor-adjacent samples. In tumors, the expression of MET proto-oncogene, receptor tyrosine kinase (MET) had a negative correlation and a positive correlation with the abundance of R. toruloides and S. tessarthra , respectively. Conclusion This study revealed the landscape of the esophageal mycobiome characterized by an altered fungal composition and bacterial and fungal ecology in ESCC. [ABSTRACT FROM AUTHOR]

Human colorectal cancer (CRC), characterized by its high morbidity and lethality, seriously threatens human health and lives. MicroRNA‐487b (miR‐487b) is currently reported to be aberrantly expressed in several tumors, but the detailed functions and underlying mechanisms of miR‐487b in CRC remain unclear. Here, we found that miR‐487b is downregulated in CRC cell lines and is markedly decreased in tumor specimens derived from CRC patients. MiR‐487b inhibits cell proliferation, migration and invasion and promotes the apoptosis of CRC cells in vitro. Statistical analysis of clinical samples indicates that miR‐487b may serve as a biomarker for early CRC diagnosis. Inverse correlations between the expression levels of MYC, SUZ12, and KRAS and that of miR‐487b exist in vitro and in CRC patient tissue specimens. Further experiments demonstrated the regulatory effects of miR‐487b on MYC, SUZ12, and KRAS, and the disruption of these genes partially restores the miR‐487b inhibitor‐induced phenotype. Additionally, miR‐487b promoter region is in a DNA hypermethylated condition and the DNA methyltransferase inhibitor 5‐aza‐2'‐deoxycytidine (5‐Aza) increases the levels of miR‐487b but suppresses the expression of MYC, SUZ12, and KRAS in a time‐ and concentration‐dependent manner in CRC cells. Collectively, miR‐487b is regulated by DNA methylation and it functions as a tumor suppressor in CRC mainly through targeting MYC, SUZ12, and KRAS. Our study provides insight into the regulatory network in CRC cells, offering a new target for treating CRC patients. [ABSTRACT FROM AUTHOR]

Highlights: [•] SOD1 is succinylated and the succinylation decreases its activity. [•] SIRT5 binds to, desuccinylates and activates SOD1. [•] Mutation of SOD1 succinylation site inhibits the growth of lung tumor cells. [ABSTRACT FROM AUTHOR]

Introduction: X-ray repair cross-complementing protein 3 (XRCC3) is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy. Methods: A systematic review and meta-analysis was performed to evaluate the predictive value of XRCC3 Thr241Met polymorphism on clinical outcomes of advanced NSCLC receiving platinum-based chemotherapy. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were analyzed. Results: A number of 11 eligible studies were identified according to the inclusion criteria. Carriers of the variant XRCC3 241Met allele were significantly associated with good response to platinum-based chemotherapy (ThrMet/MetMet vs. ThrThr: OR  = 1.509, 95% CI: 1.099–2.072, Pheterogeneity  = 0.618). The XRCC3 Thr241Met polymorphism was not associated with OS (MetMet vs. ThrThr, HR  = 0.939, 95% CI:0.651–1.356, Pheterogeneity  = 0.112) or PFS (MetMet vs. ThrThr, HR  = 0.960, 95% CI: 0.539–1.710, Pheterogeneity  = 0.198). Additionally, no evidence of publication bias was observed. Conclusions: This systematic review and meta-analysis shows that carriers of the XRCC3 241Met allele are associated with good response to platinum-based chemotherapy in advanced NSCLC, while the XRCC3 Thr241Met polymorphism is not associated with OS or PFS. [ABSTRACT FROM AUTHOR]

Aim of the study: Hepatocellular carcinoma suppressor 1 (HCCS1) has been identified as a tumor suppressor gene in the high-frequency loss of heterozygosity (LOH) region on chromosome 17p13.3 in hepatocellular carcinoma (HCC). There was also a high frequency of LOH on chromosome 17p13.3 in non-small cell lung cancer (NSCLC). Therefore, the aim of this study was to explore the expression of HCCS1 in NSCLC as well as its clinical significance. Material and methods: Real-time PCR and immunohistochemistry were performed to detect the expression level of HCCS1 mRNA and protein in NSCLC and noncancerous tissues, respectively. Further, we explored the relationship between HCCS1 expression and various clinical features in NSCLC. Results: The mRNA and protein expression of HCCS1 were both significantly lower in NSCLC samples than those in noncancerous tissues. That is, the mRNA level of HCCS1 was 0.0044 ±0.0036 and 0.0067 ±0.0054 in NSCLC samples and noncancerous tissues, respectively. The protein level of HCCS1 was 4.67 ±1.15 and 6.13 ±1.24 in NSCLC samples and noncancerous tissues, respectively. Importantly, this difference in expression was significantly correlated with tumor lymph node metastasis (TNM) in NSCLC (p < 0.05), but not with gender and age of the patients, pathological types, TNM stages, or grades of cancers (p > 0.05). Conclusion: Our results suggest that HCCS1 may be involved in NSCLC carcinogenesis. [ABSTRACT FROM AUTHOR]

A correction to the article "Novel predictors of neurosyphilis among HIV-negative syphilis patients with neurological symptoms: an observational study" is presented.

Background The rabbit infectivity test (RIT) was previously described as a highly-sensitive method for clinically detecting Treponema pallidum . But our primary study indicated this result may have changed in current antibiotics era. Methods By inoculating rabbits testis with cerebrospinal fluid (CSF) (n = 63) and exudate from hard chancre lesions (n = 13), we re-evaluated the sensitivity of RIT in modern era. All isolated T. pallidum strains from the RIT were performed for the strain type based on “CDC subtype/ tp0548 ” method. Chi-square and Fisher's exact tests were used to determine the statistical significance of differences across data sets. Results Result indicated that 2 of 63 CSF (2/63, 3.17%) and 5 of 13 lesion exudate samples (5/13, 38.47%) were positive in the RIT, with a much longer time to detection for CSF samples. Only 1 of 28 samples from patients who admitted treatment with antibiotics prior to clinical exam was positive in the RIT; while 6 of 48 patients, who admitted no recent exposure to antibiotics or was unclear about the medical history, were positive in RIT. DNA sequence analysis revealed 6 strains of 14d/f subtype and one strain of 14a/f subtype. Conclusions In conclusions, RIT is no longer a highly sensitive method for detecting T. pallidum in clinical samples as before, and is not inadequately considered to be a reference method for measuring the sensitivity of other new methods, such as the PCR. These data represent the first reexamination of the sensitivity of RIT in the post-antibiotic era with a large clinical sample. [ABSTRACT FROM AUTHOR]

Background Neurosyphilis (NS) is difficult to diagnose, especially in syphilis patients with negative cerebrospinal fluid (CSF) rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) tests. Methods We conducted a cross-sectional study and an analysis of macrophage migration inhibitory factor (MIF) in syphilitic patients to identify a novel marker for the diagnosis of NS, with a focus on probable NS (NS with negative VDRL/RPR tests). For this purpose, CSF and serum MIF concentrations were determined in 43 NS and 43 syphilis/non-NS (N-NS) patients at the Zhongshan Hospital of the Medical College of Xiamen University from July 2014 to June 2015. Sixty-three blood donors were used as healthy controls. Results NS patients had higher CSF (median [IQR]: 8.77 ng/ml [4.76–19.13]) and serum (52.58 ng/ml [28.31–95.94]) MIF concentrations than N-NS patients did (4.08 [2.21–9.68] and 34.30 [19.77–59.75], respectively). Using a cut-off point of 6.63 ng/ml, CSF MIF had a sensitivity of 74.42% and a specificity of 67.74% for the diagnosis of NS. The sensitivity was higher than that of CSF RPR (39.53%) and increased protein (48.84%) tests and similar to that of CSF pleocytosis (67.44%). Additionally, the sensitivity of CSF MIF, which was 92.31% for the diagnosis of probable NS, was higher than that of CSF pleocytosis (65.38%) and increased protein (53.85%) tests. By integrating all CSF parameters (pleocytosis, increased protein and MIF), the sensitivity would be improved to 100% by parallel testing, which would avoid missed diagnoses. Moreover, the specificity would be improved to 100% by the serial testing algorithm, which would again avoid misdiagnosis. Conclusions CSF MIF concentrations can be used as a novel CSF marker to establish or exclude a diagnosis of NS. [ABSTRACT FROM AUTHOR]

BACKGROUND Histone H2A deubiquitinase MYSM1 has recently been shown to be essential for hematopoiesis and hematopoietic stem cell (HSC) function in both mice and humans. However, conventional MYSM1 knockouts cause partial embryonic lethality and growth retardation, and it is difficult to convincingly remove the effects of environmental factors on HSC differentiation and function. MATERIAL AND METHODS MYSM1 conditional knockout (cKO) mice were efficiently induced by using the Vav1-cre transgenic system. The Vav-Cre MYSM1 cKO mice were then analyzed to verify the intrinsic role of MYSM1 in hematopoietic cells. RESULTS MYSM1 cKO mice were viable and were born at normal litter sizes. At steady state, we observed a defect in hematopoiesis, including reduced bone marrow cellularity and abnormal HSC function. MYSM1 deletion drives HSCs from quiescence into rapid cycling, and MYSM1-deficient HSCs display impaired engraftment. In particular, the immature cycling cKO HSCs have elevated reactive oxygen species (ROS) levels and are prone to apoptosis, resulting in the exhaustion of the stem cell pool during stress response to 5-FU. CONCLUSIONS Our study using MYSM1 cKO mice confirms the important role of MYSM1 in maintaining HSC quiescence and survival.

This study aimed to determine whether a serological response could predict the normalization of cerebrospinal fluid (CSF) abnormalities at 6 months after treatment in human immunodeficiency virus (HIV)-negative neurosyphilis patients. A total of 123 neurosyphilis patients were recruited at baseline, 58 of these patients undergoing treatment, repeated CSF examinations and serological tests for syphilis at 6 months after treatment were included in the follow-up study. Before treatment, the CSF rapid plasma reagin (RPR) titer, CSF Treponema pallidum particle agglutination (TPPA) titer, CSF leukocyte count, and CSF protein concentration were correlated with both serum RPR and TPPA titers. At 6 months after treatment, 28 and nine patients achieved serological responses of RPR and TPPA tests, respectively. The sensitivities of the serological response of RPR and TPPA tests for identifying the normalization of CSF abnormalities were 60.0∼83.3% and 17.1~22.2%, respectively; and 75.0∼91.3% of patients showing serological response of RPR test also achieved CSF normalization, suggesting that the serological response could predict CSF normalization to some degree. Particularly, in patients with ≥8-fold decreases in the serum RPR titer, the CSF RPR, CSF leukocyte count, and CSF protein concentration had normalized, and follow-up lumbar puncture could be reduced considering the resolution of neurological symptoms.

Background: Known predictors of neurosyphilis were mainly drawn from human immunodeficiency virus (HIV)-infected syphilis patients, which may not be applicable to HIV-negative populations as they have different characteristics, particularly those with neurological symptoms. This study aimed to identify novel predictors of HIV-negative symptomatic neurosyphilis (S-NS)., Methods: From June 2005 to June 2015, 370 HIV-negative syphilis patients with neurological symptoms were recruited, consisting of 191 S-NS patients (including 123 confirmed neurosyphilis and 68 probable neurosyphilis patients) and 179 syphilis/non-neurosyphilis (N-NS) patients. Clinical and laboratory characteristics of S-NS were compared with N-NS to identify factors predictive of S-NS. Serum rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and their parallel testing format for screening S-NS were evaluated., Results: The likelihood of S-NS was positively associated with the serum RPR and TPPA titers. The serum TPPA titers performed better than the serum RPR titers in screening S-NS. The optimal cut-off points to recognize S-NS were serum RPR titer ≥1:4 and serum TPPA titer ≥1:2560 respectively. A parallel testing format of a serum RPR titer ≥1:2 and serum TPPA titer ≥1:1280 screened out 95.8% of S-NS and all confirmed cases of neurosyphilis. S-NS was independently associated with male sex, serum RPR titer ≥1:4, serum TPPA titer ≥1:2560, and elevated serum creatine kinase. Concurrence of these factors increased the likelihood of S-NS., Conclusions: Quantitation of serum TPPA is worthwhile and performs better than serum RPR in screening S-NS. Serum RPR, serum TPPA, male sex, and serum creatine kinase can predict S-NS. Moreover, patients with both a serum RPR titer <1:2 and a serum TPPA titer <1:1280 have a low probability of S-NS, suggesting that it is reasonable to reduce lumbar punctures in such individuals.

Aim of the Study: Hepatocellular carcinoma suppressor 1 (HCCS1) has been identified as a tumor suppressor gene in the high-frequency loss of heterozygosity (LOH) region on chromosome 17p13.3 in hepatocellular carcinoma (HCC). There was also a high frequency of LOH on chromosome 17p13.3 in non-small cell lung cancer (NSCLC). Therefore, the aim of this study was to explore the expression of HCCS1 in NSCLC as well as its clinical significance., Material and Methods: Real-time PCR and immunohistochemistry were performed to detect the expression level of HCCS1 mRNA and protein in NSCLC and noncancerous tissues, respectively. Further, we explored the relationship between HCCS1 expression and various clinical features in NSCLC., Results: The mRNA and protein expression of HCCS1 were both significantly lower in NSCLC samples than those in noncancerous tissues. That is, the mRNA level of HCCS1 was 0.0044 ±0.0036 and 0.0067 ±0.0054 in NSCLC samples and noncancerous tissues, respectively. The protein level of HCCS1 was 4.67 ±1.15 and 6.13 ±1.24 in NSCLC samples and noncancerous tissues, respectively. Importantly, this difference in expression was significantly correlated with tumor lymph node metastasis (TNM) in NSCLC (p < 0.05), but not with gender and age of the patients, pathological types, TNM stages, or grades of cancers (p > 0.05)., Conclusion: Our results suggest that HCCS1 may be involved in NSCLC carcinogenesis.

A novel angular probe using the Fabry-Perot etalon and angular scanning technique is proposed for absolute angular displacement determinations in this paper. The measurement theory is first derived, a setup constructed to implement the angular probe is then introduced and analyzed, and the experimental results from the uses of the setup are finally presented. The setup analyses reveal that the probe is with high measurement resolution and sensitivity. The experimental results not only confirm the validity, stability, accuracy, and repeatability, but also show an application of the angular probe.