[Determination of 8 N-nitrosamines in the workplace air by GC-MS/MS method].

Objective: To establish a method for the determination of eight N-nitrosamines (N-nitrosodimethylamine, N-nitrosodimethylamine, N-nitrosomethylmethylamine, N-nitrosodibutylamine, N-nitrosopropylamine, N-nitrosomorpholine, N-nitrosodianiline and N-nitrosopiperidine) in the air of workplace by gas chromatography-tandem mass spectrometry (GC-MS/MS) . Methods: From January to August 2023, eight N-nitrosamines in the air of workplace were collected by ThermoSorb/N column, eluted with 4 ml methanol-dichloromethane (1∶1 volume ratio), separated by VF-624 ms capillary column, detected by multiple reaction monitoring mode and quantified by external standard method. The detection limit and precision of the method were also analyzed. Results: The linear range of the method for the determination of eight N-nitrosamines was 1.0-20.0 µg/L, the correlation coefficient was 0.9993-0.9999, the detection limit was 0.051-0.132 µg/L, and the minimum quantitative concentration was 0.030-0.078 µg/m(3) (calculated by collecting 22.5 L of air sample and eluting with 4.0 ml stripping liquid). The within-run precisions were 2.05%-6.89% and the between-run precisions were 2.41%-8.26%. The desorption rates were 67.20%-102.60%. The sample can be kept at least 7 days at 4 ℃. Conclusion: GC-MS/MS method for the determination of eight N-nitrosamines in workplace air has high sensitivity and good precision, and can accurately determine the content of eight N-nitrosamines in workplace air.

[Two cases of Dent disease type 1 with Bartter-like phenotype and literature review].

The clinical presentation, treatment, and follow-up of two boys with type 1 Dent disease who exhibited a Bartter-like phenotype were retropectively analysed. The related literature of pediatric patients with type 1 Dent disease who had hypokalemia and metabolic alkalosis was screened through databases such as PubMed, CNKI, and Wanfang until February 1, 2024, and common features among these patients were summarized through literature review. A total of 7 literatures were included, and 9 children were included in the analysis. All patients were male, presenting with significant low molecular weight proteinuria and hypercalciuria. Other prominent characteristic phenotypes included short stature (7/8), hypophosphatemia (8/9), and rickets (6/8). Seven previously reported patients had missense or nonsense mutations, while 2 patients in this study carried possible pathogenic mutations in the CLCN5 gene, c.315+2T>A (p.?) and c.584dupT (p.I196Yfs*6), respectively. Five patients were able to maintain blood potassium levels around 3 mmol/L with oral potassium chloride solution combined with non-steroidal anti-inflammatory drugs (ibuprofen or indomethacin). The follow-up showed that 2 patients developed chronic kidney disease stage 4 and stage 3 at the age of 13 and 21 years, respectively. The phenotypic overlap between Dent disease and Batter syndrome is considerable,with the distinguishing feature being the presence of significant low molecular weight proteinuria. Patients with type 1 Dent disease presenting with the Bartter-like phenotype have a high prevalence of short stature, hypophosphatemia, and rickets. Non-steroidal anti-inflammatory drugs can be used to correct hypokalemia in patients under periodic renal function assessment.

[Olfactory neuroblastoma in children: clinical analysis of five cases].

The clinical data of five patients diagnosed with olfactory neuroblastoma (ONB) who were admitted to the Department of Pediatrics, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2012 to January 2024 were retrospectively analyzed. Two males and three females aged 6.2 (5.7-15.8) years were included. The symptoms mainly covered nasal congestion, increased nasal secretions, headache, decreased vision and so on. Pathological grade Ⅱ, Ⅲ and Ⅳ was identified in two cases, one case and two cases, respectively. Modified Kadish stage B, C and D was detected in one case, two cases and two cases, respectively. All patients underwent surgery, chemotherapy, and radiation therapy. Among the five patients, four survived and one died. The follow-up time was 22.3 (10.4-56.4) months, and the recurrence rate was 0. ONB should be suspected when tumors are presented in the upper and middle parts of the nasal cavity, especially dumbbell shaped masses that grow towards the nasal cavity and intracranial area based on imaging. The multimodality therapy of ONB comprising of surgery and chemotherapy, can achieve good therapeutic effects and prognosis, but long-term follow-up is required.

[Prediction model related to 6-year risk of frailty in older adults aged 65 years or above in China].

Objective: To develop a prediction tool for 6-year incident risk of frailty among Chinese older adults aged 65 years or above. Methods: Data from the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 was used, including 13 676 older adults aged 65 years or above who were free of frailty at baseline. Key predictors of frailty were identified via the least absolute shrinkage and selection operator (LASSO) method, and were thereafter used to predict the incident frailty based on the Cox proportional hazards regression model. The model was internally validated by 2 000 Bootstrap resamples and evaluated for the performance of discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curve, respectively. The net benefit of the developed prediction tool was evaluated by decision-curve analysis. Results: The M(Q1, Q3) age and follow-up time of the participants were 81.0 (71.0, 90.0) years and 6.0 (4.1, 9.2) years, respectively. A total of 4 126 older persons (30.2%) were recorded with frailty incidents during the follow-up, with the corresponding incidence density of 41.8/1 000 person-years. A total of 15 key predictors of frailty were selected by LASSO, namely, age, sex, race, education years, meat consumption, tea drinking, performing housework, raising domestic animals, playing cards or mahjong, and baseline status of visual function, activities of the daily living score, instrumental activities of the daily living score, hypertension, heart disease, and self-rated health. The prediction model was internally validated with an AUC of 0.802, with the max Youden's index of 0.467 at a risk threshold of 19.0%. The calibration curve showed high consistency between predicted probabilities and observed proportions of frailty events. The decision curve indicated that higher net benefits could be obtained via the prediction model than did strategies based on intervention in all or none participants for any risk threshold less than 59%, and the model-based net benefit was estimated to be 0.10 at a risk threshold of 19.0%. Conclusions: The herein developed 6-year incident risk prediction model of frailty, based on easily accessible questionnaires and physical examination variables, has good predictive performance. It has application potential in identifying populations at high risk of incident frailty.

[Advances in thoracic consolidation radiotherapy after first-line immunotherapy combined with chemotherapy for extensive stage small cell lung cancer].

Small cell lung cancer (SCLC) accounts for about 13%~17% of primary bronchial lung cancer. Due to its rapid growth rate, aggressive behavior, early metastasis and poor prognosis, about 70% of patients were diagnosed with extensive-stage (ES) disease. Although most ES-SCLC patients are sensitive to initial chemotherapy, local recurrence and distant metastasis develop in the short term. Immunotherapy has brought the dawn to overcome it. At present, immune checkpoint inhibitor combined with chemotherapy has become an important strategy as first-line therapy for ES-SCLC. Nevertheless, patients are still at a high risk of chest lesion recurrence after initial systemic therapy. Whether the addition of thoracic consolidation radiotherapy (TRT) can reduce chest lesion recurrence rate remains to be determined. In this review, we summarized the latest research progress in the mode of first-line chemotherapy combined with immunotherapy followed by TRT in ES-SCLC, aiming to provide reference for clinical practice.

[Clinical characteristics and prognosis of 5 children with maturity onset of diabetes of the young 12 subtype].

Objective: To analyze the genetic and clinical characteristics, treatment and prognosis of patients diagnosed with maturity onset of diabetes of the young (MODY) 12 subtype. Methods: This retrospective study collected and analyzed data from 5 children with MODY12 subtype caused by ABCC8 gene variants who underwent inpatient and outpatient genetic testing at Beijing Children's Hospital from January 2016 to December 2023. Their clinical and genetic features, treatment, and follow-up results were analyzed. Results: Among the 5 patients with MODY12 subtype, 4 were male and 1 was female, with an age of 13.4 (5.5, 14.6) years. Four of the patients were born large for gestational age, while one was born small for gestational age. Two patients were overweight or obese. Three patients exhibited typical symptoms of diabetes, while 2 were incidentally found to have elevated blood glucose level. One patient was found to have diabetic ketoacidosis at onset, who was diagnosed with congenital hyperinsulinism during the neonatal period and received diazoxide treatment, and experienced intellectual developmental delay. All 5 patients had autosomal dominant inherited diabetes within 3 generations. The fasting blood glucose at onset was 7.5 (6.5, 10.0) mmol/L, the haemoglobin A1c (HbA1c) was 11.8% (7.5%, 13.5%), and the fasting C-peptide was 1.2 (1.1, 2.2) µg/L. The duration of follow-up was 15 (9, 32) months. One patient underwent lifestyle intervention, 2 received metformin orally, 1 received insulin therapy, and the other received subcutaneous injection of insulin combined with sulfonylurea orally. At the last follow-up, the median fasting blood glucose was 6.1 (5.1, 7.0) mmol/L, the HbA1c was 5.9% (5.7%, 7.1%), and the fasting C-peptide was 1.7 (0.9, 2.9) µg/L. One patient developed diabetic retinopathy. There were 4 missense variations in ABCC8 gene and one in-frame deletion, all of which were maternally inherited heterozygotes. Conclusions: MODY12 subtype is a heterogeneous disorder with the age of onset from infancy to adolescence. It can present as mild hyperglycemia or diabetic ketoacidosis, and has a high incidence of obesity. Definitive diagnosis can be achieved through genetic test, and individualized treatment is recommended based on glucose levels.

[Pulse oximetric saturation/fraction of inspired oxygen and partial pressure of oxygen/fraction of inspired oxygen in diagnosing acute respiratory distress syndrome: which is better?]

Acute Respiratory Distress Syndrome (ARDS) is distinguished by hypoxemia, contributing to heightened morbidity, elevated mortality rates, and substantial healthcare expenses, thereby imposing a significant burden on patients and society. Presently, effective treatments for ARDS are lacking, emphasizing the pivotal role of early diagnosis and timely intervention in its successful management. The partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2, P/F) has traditionally served as a crucial metric for assessing patient hypoxemia and disease severity. While relatively accurate, its reliance on advanced technical expertise and specific medical equipment conditions constrains its implementation in areas with underdeveloped medical standards, resulting in missed diagnoses and treatments for ARDS patients. Conversely, the Pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2, S/F) has garnered increasing attention owing to its straightforward, non-invasive, and sustainable monitoring attributes. This article seeks to meticulously compare the correlation, accuracy, and clinical feasibility of S/F with P/F in ARDS diagnosis, so as to propose diagnostic indicators for more quickly and accurately assessing the oxygenation status of ARDS patients.

Comparison of urinary incontinence following three different prostate apex disconnection techniques in transurethral thulium laser prostatectomy.

OBJECTIVE: This study investigates the incidence of urinary incontinence following transurethral thulium laser prostatectomy with three different prostate apex disconnection techniques: semi-separation, pre-separation, and post-separation. The findings aim to provide references for clinical treatment. PATIENTS AND METHODS: A retrospective analysis was conducted on 74 patients treated with transurethral thulium laser prostatectomy for prostatic hyperplasia from April 2022 to March 2023. Complete clinical and follow-up data were available for 52 patients. Clinical and follow-up data were collected for these patients. A comparison was made of urinary incontinence following the three different types of prostate apex disconnection in transurethral thulium laser prostatectomy. RESULTS: In this study, the immediate postoperative urinary incontinence rate for transurethral thulium laser prostatectomy was 9.62% (5/52), the short-term incontinence rate was 11.54% (5/52), and the long-term incontinence rate was 9.62% (5/52). The immediate postoperative incontinence rates for semi-separation, pre-separation, and post- separation were 8.33% (1/12), 8.33% (2/24), and 12.5% (2/16), respectively. The short-term incontinence rates for semi-separation, pre-separation, and post-separation were 8.33% (1/12), 8.33% (2/24), and 18.75% (3/16), respectively. The long-term incontinence rates for semi-separation, pre-separation, and post-separation were 8.33% (1/12), 8.33% (2/24), and 12.5% (2/16), respectively. CONCLUSIONS: The incidence of urinary incontinence following transurethral thulium laser prostatectomy was lower with semi-separation and pre-separation compared to post-separation.

AMPK inhibition sensitizes acute leukemia cells to BH3 mimetic-induced cell death.

BH3 mimetics, including the BCL2/BCLXL/BCLw inhibitor navitoclax and MCL1 inhibitors S64315 and tapotoclax, have undergone clinical testing for a variety of neoplasms. Because of toxicities, including thrombocytopenia after BCLXL inhibition as well as hematopoietic, hepatic and possible cardiac toxicities after MCL1 inhibition, there is substantial interest in finding agents that can safely sensitize neoplastic cells to these BH3 mimetics. Building on the observation that BH3 mimetic monotherapy induces AMP kinase (AMPK) activation in multiple acute leukemia cell lines, we report that the AMPK inhibitors (AMPKis) dorsomorphin and BAY-3827 sensitize these cells to navitoclax or MCL1 inhibitors. Cell fractionation and phosphoproteomic analyses suggest that sensitization by dorsomorphin involves dephosphorylation of the proapoptotic BCL2 family member BAD at Ser75 and Ser99, leading BAD to translocate to mitochondria and inhibit BCLXL. Consistent with these results, BAD knockout or mutation to BAD S75E/S99E abolishes the sensitizing effects of dorsomorphin. Conversely, dorsomorphin synergizes with navitoclax or the MCL1 inhibitor S63845 to induce cell death in primary acute leukemia samples ex vivo and increases the antitumor effects of navitoclax or S63845 in several xenograft models in vivo with little or no increase in toxicity in normal tissues. These results suggest that AMPK inhibition can sensitize acute leukemia to multiple BH3 mimetics, potentially allowing administration of lower doses while inducing similar antineoplastic effects.

Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer.

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1. Furthermore, we find that the infiltration of POSTN+ fibroblasts and SPP1+ macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8+ T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma.

[Platycodin D improves pulmonary fibrosis in mice by down-regulating TRPC6 expression and reducing ROS production in lung fibroblasts].

OBJECTIVE: To assess the effect of platycodin D (PD) for alleviating pulmonary fibrosis in mice and explore the underlying mechanism. METHODS: C57BL/6J mouse models of pulmonary fibrosis induced by bleomycin injection into the airway were treated with daily intragastric administration of 10 mg/kg PD for 28 days. The changes of pulmonary fibrosis and the expression and distribution of transient receptor potential cation channel subfamily C member 6 (TRPC6) were evaluated with immunohistochemistry, HE staining and Sirius Red staining. Western blotting was used to detect α-SMA expression in the lung tissues of the mice. Primary cultures of mouse lung fibroblasts were pretreated with PD (2.5, 5.0, and 10 µmol/L) or larixyl acetate (LA; 10 µmol/L) before exposure to 10 ng/mL transforming growth factor-ß1 (TGF-ß1), and the changes in cell survival rate, expressions of collagen Ⅰ, α-SMA and TRPC6, reactive oxygen species (ROS) production, mitochondrial membrane potential, and cell proliferation capacity were assessed. Network pharmacology analysis was performed to explore the mechanism by which PD alleviated pulmonary fibrosis. RESULTS: PD treatment significantly alleviated pulmonary fibrosis and reduced α-SMA expression in BLM-induced mouse models (P<0.05). In TGF-ß1-induced primary mouse lung fibroblasts, PD effectively inhibited the cell proliferation, reduced ROS production (P<0.0001), rescued the reduction of mitochondrial membrane potential (P<0.001), and inhibited the expressions of α-SMA and collagen Ⅰ (P<0.05). Network pharmacology analysis suggested that TRPC6 mediated the effect of PD for alleviating pulmonary fibrosis. Immunohistochemistry showed that PD significantly reduced TRPC6 expression in the lung tissues of BLM-induced mice. In primary mouse lung fibroblasts, PD significantly inhibited TGF-ß1-induced TRPC6 expression (P<0.05), and LA treatment obviously lowered the expression levels of TRPC6, α-SMA and collagenⅠ (P<0.05). CONCLUSION: PD alleviated pulmonary fibrosis in mice possibly by down-regulating TRPC6 and reducing ROS production.

[Echocardiographic two-dimensional strain evaluation of right ventricular function in healthy adults].

Objective: To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender. Methods: This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient (ICC). Results: A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions: Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.

[Determination of acetone in urine by headspace gas chromatography-mass spectrometry].

Objective: To establish a method for determination of acetone in urine by headspace gas chromatography-mass spectrometry. Methods: From March to June 2021, the 3.0 ml urine sample was placed in a headspace bottle with 4.0 g of anhydrous sodium sulfate and sealed. Equilibration time was 30 min at 85 ℃. The separation was carried out on a DB-5MS column. The urine sample was detected by mass spectrometry and quantified by external standard method. Results: The method for the determination of acetone in urine by headspace gas chromatography-mass spectrometry had good linearity in the range of 51.2-1024.0 µg/L, and the correlation coefficient was 0.9995. The detection limit and the lower limit of quantification of acetone were 16.4 µg/L and 54.6 µg/L. The average recoveries of samples ranged from 94.9% to 96.8%. The intra-assay precision and inter-assay precision were both less than 10%. Samples can be stored at least 7 d at 4 ℃ or -20 ℃. Conclusion: This method has simple sample preparation and high sensitivity. It can be used for monitoring and evaluation of urinary acetone in the general population and occupationally exposed populations.

[Lead exposure aggravates Aß1-42-induced microglial activation and copper ion accumulation in microglial cells].

OBJECTIVE: To investigate the effect of lead (Pb) exposure on Aß1-42-induced microglial activation and copper ion accumulation in microglial cells and explore the regulatory mechanism of Pb-induced aggravation of Alzheimer's disease (AD)-like pathology. METHODS: Cultured microglial BV2 cells were treated with different concentrations of Aß1-42, lead acetate or their combination for 12 h, and the changes in cell viability and morphology were evaluated. Immunofluorescence assay was performed to detect iNOS and oxidative stress level in the treated cells, and the release of inflammatory factors was detected using ELISA. Western blotting and inductively coupled plasma-mass spectrometry (ICP-MS) were used to detect the expressions of CTR1 and ATP7A proteins and copper content in the cells. RESULTS: Treatment with 15 and 20 µmol/L Aß1-42 for 12 h significantly lowered the viability of BV2 cells. Treatment with Aß1-42 at 10 µmol/L for 12 h obviously increased the release of iNOS, TNF-α and IL-6 in the cells (P<0.05), and its combination with 15 or 20 µmol/L lead acetate more strongly lowered BV2 cell viability (P<0.05). Compared with 10 µmol/L Aß1-42 treatment alone, 10 µmol/L Aß1-42 combined with 10 µmol/L lead acetate for 12 h caused more obvious microglial activation, as manifested by enlarged cell bodies, increased cell protrusions and elongation, enhanced release of iNOS, TNF-α, IL-6, IL-1ß and ROS, and increased intracellular copper ion accumulation and expression of copper transporter CTR1 (P<0.05). Compared with the conditioned medium from activated BV2 cells, which caused obvious injuries in hippocampal neuron HT22 cells (P<0.001), the medium from BV2 cells treated with NAC and the copper ion chelating agent TM caused milder injuries in HT22 cells (P<0.05). CONCLUSION: Lead exposure aggravates neuronal damage caused by Aß1-42-treated microglial cells by increasing copper ion accumulation, oxidative stress, and inflammatory factor release to trigger microglial activation.

[Determination of phenylglyoxylic acid and mandelic acid in urine by ultra high performance liquid chromatography tandem mass spectrometry].

Objective: To develop a method for the analysis of phenylglyoxylic acid (PGA) and mandelic acid (MA) in urine by ultra-high performance liquid chromatography tandem mass spectrometry. Methods: The study was conducted in April 2022. Urine samples were directly diluted with the initial mobile phase, separated by Waters HSS T3 column after passing through the membrane, and analyzed under negative ionization mode (ESI(-)) and multiple reaction monitoring (MRM) conditions, the contents of PGA and MA in human urine were quantitatively determined by external standard method. Results: The determination of PGA and MA showed a good linear relationship within the range of 10-1000 ng/ml, with a correlation coefficient of 0.9999. The linear regression equation of PGA was y=1141.4x+2157.3, the detection limit and lower limit of quantification of the method were 0.081 ng/ml and 0.269 ng/ml, and the recovery rate was 90.47%-99.83%. The linear regression equation of MA was y=62.8x+140.3, the detection limit and lower limit of quantification of the method were 0.551 ng/ml and 1.836 ng/ml, and the recovery rate was 92.75%-101.09%. The intra and inter batch precision of PGA and MA were both<5%. Conclusion: An ultra-high performance liquid chromatography tandem mass spectrometry method for the analysis of PGA and MA in urine was established.The sample pretreatment operation is simple, and the accuracy and precision of the method meet the standard requirements. It can be used for monitoring and evaluating PGA and MA in urine of the general population and occupational contact population.

ZNF432 stimulates PARylation and inhibits DNA resection to balance PARPi sensitivity and resistance.

Zinc finger (ZNF) motifs are some of the most frequently occurring domains in the human genome. It was only recently that ZNF proteins emerged as key regulators of genome integrity in mammalian cells. In this study, we report a new role for the Krüppel-type ZNF-containing protein ZNF432 as a novel poly(ADP-ribose) (PAR) reader that regulates the DNA damage response. We show that ZNF432 is recruited to DNA lesions via DNA- and PAR-dependent mechanisms. Remarkably, ZNF432 stimulates PARP-1 activity in vitro and in cellulo. Knockdown of ZNF432 inhibits phospho-DNA-PKcs and increases RAD51 foci formation following irradiation. Moreover, purified ZNF432 preferentially binds single-stranded DNA and impairs EXO1-mediated DNA resection. Consequently, the loss of ZNF432 in a cellular system leads to resistance to PARP inhibitors while its overexpression results in sensitivity. Taken together, our results support the emerging concept that ZNF-containing proteins can modulate PARylation, which can be embodied by the pivotal role of ZNF432 to finely balance the outcome of PARPi response by regulating homologous recombination.

[Survey on the cognition of the "undetectable equals untransmittable" concept among HIV-infected men who have sex with men receiving antiviral treatment].

Objective: To explore the cognition of the "undetectable equals untransmittable" ("U=U") concept and associated factors among HIV-infected men who have sex with men (MSM) receiving antiviral treatment (ART) in Shenzhen, and provide evidence for designing promotion and advocacy strategies for the "U=U" concept. Methods: We recruited HIV-infected MSM receiving ART using convenient sampling method combined with routine follow-up in Shenzhen through conducting observational survey. The sample size was estimated to be 475. A questionnaire was administered to collect socio-demographic characteristics, sexual behaviors, ART, viral load testing and the cognition towards "U=U" in HIV-infected MSM. Logistic regression was used to access factors associated with acceptance of "U=U". Results: A total of 490 HIV-infected MSM receiving ART were recruited. Of whom, 60.2% (295/490) were aware of "U=U" and 50.6% (248/490) accepted "U=U". Multiple logistic regression showed that participants who had an educational level of college or above (aOR=1.76,95%CI: 1.12-2.75) were more likely to accept "U=U". Those who had no local residency (aOR=0.51,95%CI: 0.29-0.92), had viral load >0 copies/ml in the last testing (aOR=0.61,95%CI: 0.38-0.98) and were unaware of "U=U" (aOR=0.13, 95%CI: 0.09-0.21), were less likely to accept "U=U". Conclusions: HIV-infected MSM receiving ART had a low cognition level of "U=U" in Shenzhen. Promotion and advocacy on this concept through healthcare workers should be enhanced in combination with routine follow-up in order to improve their ART adherence and outcome of treatment. Furthermore, developing related guidelines on "U=U" according to the characteristics of HIV-infected individuals is warranted to improve the normalization of promotion and advocacy on "U=U".

[Evaluation of effects of comprehensive intervention based on key persons on AIDS-related high-risk behaviors in male sex workers in entertainment venues].

Objective: To evaluate the effect of comprehensive intervention model based on key persons in entertainment venues on the incidence of AIDS-related high-risk behaviors in male sex workers (MSW). Data from this study thus can be used to provide compelling evidence for the wider implementation of the intervention model. Methods: In this randomized controlled trial, MSW were recruited and followed-up from May to December, 2021 in entertainment venues in Wuxi, Jiangsu Province, with an estimated sample size of 320. The MSW in the intervention group were provided with comprehensive interventions via key persons in entertainment venues compared with the control group receiving routine interventions. The effect of the intervention model was assessed by comparing the behavioral differences between these two groups and in the intervention group before and after intervention. Results: A total of 330 MSW were recruited at baseline survey, in which 168 were divided into intervention group and 162 into control group. There was no significant difference in socio-demographic characteristics between two groups (all P>0.05). After intervention for 6 months, the rate of consistent condom use in commercial homosexual activities in the intervention group was 79.5% (101/127), higher than 63.2% (74/117) in the control group, and in the intervention group, 90.1% (73/81) of MSW used condom consistently in heterosexual activities, higher than in the control group (59.6%, 59/99) . Compared with 30.8% (36/117) of MSW with drug abuse history in the control group, a lower proportion of 9.4% (12/127) was observed in the intervention group. Differences in all of aforementioned variables were significant (all P<0.05). After intervention, the incidence of group sex was 3.9% (5/127) in the intervention group and 9.4% (11/117) in the control group, the incidence of anal sex post-alcohol consumption was 40.2% (51/127) in the intervention group and 32.5% (38/117) in control group, the differences were not significant (all P>0.05). Conclusions: The intervention model based on key persons in entertainment venues could promote consistent condom use in MSW in both commercial homosexual and heterosexual activities and help them reduce drug abuse, but had no significant effect on decreasing group sex and anal sex after alcohol consumption. It is crucial to improve the intervention model according to the specific characteristics of MSW in order to enhance the effects of comprehensive intervention.