Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan.

BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.

Disclosure Concerns and the Correlation Among Gay, Bisexual, and Other Men Who Have Sex With Men Living With HIV Receiving Antiretroviral Therapy in Taiwan.

Gay, bisexual, and other men who have sex with men (GBMSM) are associated with the widespread human immunodeficiency virus (HIV) transmission in Taiwan. Additionally, little is known about disclosure patterns and rates, as well as factors influencing disclosure, among GBMSM living with HIV in the country. HIV prevention for GBMSM is effective when HIV status is disclosed. For instance, GBMSM disclosing their HIV status can result in early pre-exposure prophylaxis with a serodiscordant partner. In this cross-sectional study of 200 GBMSM living with HIV conducted from June to November 2020, we assessed internalized homophobia (IHP Scale) and social support (Multidimensional Scale of Perceived Social Support), as well as self-reported disclosure and non-disclosure. Among the participants, 75.5% revealed their HIV status within 3 months of diagnosis. Younger age, occupation type, and number of sexual partners were some factors associated with disclosure. Those receiving more social support and who experienced less IHP were more likely to reveal their HIV status. On the contrary, older GBMSM and GBMSM living with HIV who worked in educational enterprises still experienced severe IHP. Policymakers and healthcare practitioners should be aware of the problems faced by GBMSM living with HIV and offer practical assistance to improve their mental health.

Comparable clinical outcomes with same-day versus rapid initiation of antiretroviral therapy in Taiwan.

OBJECTIVES: WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. METHODS: We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. RESULTS: At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. CONCLUSIONS: SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.

The value of serum LBP and CXCL-10 in the differential diagnosis of acute upper respiratory tract bacterial infection in children and its influencing factors / 国际检验医学杂志

Objective To investigate the differential diagnostic value of serum lipopolysaccharide binding protein(LBP)and serum CXC chemokine ligand-10(CXCL-10)in children with acute upper respiratory tract bacterial infection and its influencing factors.Methods A total of 90 children with acute upper respiratory tract infection admitted to the hospital from July 2021 to June 2022 were enrolled in the study as the study group,and 40 healthy children who underwent physical examination in the hospital during the same period were enrolled as the healthy group.According to the results of sputum bacterial culture,the study group was divided into bacterial infection group(51 cases)and non-bacterial infection group(39 cases).The serum levels of LBP and CXCL-10 were detected by using enzyme-linked immunosorbent assay.Receiver operating charac-teristic(ROC)curve was used to evaluate the value of serum LBP and CXCL-10 in the differential diagnosis of acute upper respiratory tract bacterial infection in children.Multivariate Logistic regression was used to ana-lyze the influencing factors of acute upper respiratory tract bacterial infection in children.Results The serum levels of LBP and CXCL-10 in the study group were higher than those in the healthy group(P＜0.05).The se-rum levels of LBP and CXCL-10 in the bacterial infection group were higher than those in the non-bacterial in-fection group(P＜0.05).The area under curves(AUCs)of serum LBP and CXCL-10 alone and in combina-tion for the diagnosis of acute upper respiratory tract bacterial infection in children were 0.779(95％CI:0.724-0.822),0.843(95％CI:0.796-0.898),0.906(95％CI:0.852-0.959),respectively.Compared with the non-bacterial infection group,the bacterial infection group had significantly higher proportions of family members with smoking,iron deficiency,and calcium deficiency,annual average times of antibacterial drug use,and serum LBP and CXCL-10 levels(P＜0.05).Logistic multivariate regression analysis showed that the av-erage annual use of antibiotics ≥2 times(OR=2.305,95％CI:1.483-3.582),LBP≥104.26 ng/mL(OR=2.573,95％CI:1.446-4.578)and CXCL-10≥112.98 pg/mL(OR=1.208,95％CI:0.110-1.314)were the influencing factors of acute upper respiratory tract bacterial infection in children(P＜0.05).Conclusion The elevated serum LBP and CXCL-10 levels are closely related to acute upper respiratory tract bacterial infection in children,which can be used as indicators for the differential diagnosis of acute upper respiratory tract bacte-rial infection,and the combination of the two has higher diagnostic efficiency.

The impact of apoB/apoA1 on lupus nephritis and renal insufficiency and its diagnostic value / 中国医师杂志

Objective:To analyze the impact and diagnostic value of apoB/apoA1 on lupus nephritis (LN) and its renal dysfunction.Methods:A total of 134 patients diagnosed with systemic lupus erythematosus (SLE) at the Taihe Hospital of Anhui University of Traditional Chinese Medicine from July 2019 to January 2023 were selected and divided into LN group ( n=82) and simple SLE group ( n=52). According to the glomerular filtration rate (e-GFR), LN was divided into a group with normal renal function ( n=42) and a group with renal insufficiency ( n=40). We compared the differences in clinical data between different groups and analyzed the diagnostic value of apoB, apoA1, and apoB/apoA1 for LN and its renal insufficiency. Results:The results of binary logistic regression analysis showed that apoB/apoA1, SLE disease activity index (SLEDAI), anti double stranded DNA (dsDNA), complement 3 (C3), and albumin (ALB) were independent influencing factors for LN ( OR=4.033, 1.179, 3.148, 0.374, 0.879, all P<0.05). The area under the curve (AUC) of apoB, apoA1, and apoB/apoA1 for diagnosing LN were 0.623, 0.662, and 0.742, respectively. The diagnostic efficacy of apoB/apoA1 was higher than that of apoB and apoA1, and the differences are statistically significant (all P<0.05). Regardless of whether confounding factors were adjusted or not, apoB/apoA1 were all risk factors for LN with e-GFR>60 ml/(min·1.73 m 2), e-GFR 30-60 ml/(min·1.73 m 2), and e-GFR<30 ml/(min·1.73 m 2) (all P<0.05). ApoB/apoA1, anti dsDNA, C3, and ALB were all independent influencing factors for renal insufficiency LN ( OR=3.778, 2.669, 0.415, 0.884, all P<0.05). The AUC for diagnosing renal insufficiency LN in apoB, apoA1, and apoB/apoA1 were 0.623, 0.640, and 0.730, respectively. The diagnostic efficacy of apoB/apoA1 was higher than that of apoB and apoA1, and the differences were statistically significant (all P<0.05). Conclusions:ApoB/apoA1 is an independent influencing factor for the occurrence of LN and renal insufficiency LN, and has good diagnostic value for LN and renal insufficiency LN.

Treatment responses to integrase strand-transfer inhibitor-containing antiretroviral regimens in combination with short-course rifapentine-based regimens for latent tuberculosis infection among people with HIV.

BACKGROUND: Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor (InSTI)-containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with HIV (PWH). METHODS: From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment, and the secondary outcomes included treatment completion rate and safety of LTBI regimens. RESULTS: During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200 copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate. CONCLUSION: Combinations of short-course rifapentine-based regimens and InSTI-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events.

Loss of ATOH1 in Pit Cell Drives Stemness and Progression of Gastric Adenocarcinoma by Activating AKT/mTOR Signaling through GAS1.

Gastric cancer stem cells (GCSCs) are self-renewing tumor cells that govern chemoresistance in gastric adenocarcinoma (GAC), whereas their regulatory mechanisms remain elusive. Here, the study aims to elucidate the role of ATOH1 in the maintenance of GCSCs. The preclinical model and GAC sample analysis indicate that ATOH1 deficiency is correlated with poor GAC prognosis and chemoresistance. ScRNA-seq reveals that ATOH1 is downregulated in the pit cells of GAC compared with those in paracarcinoma samples. Lineage tracing reveals that Atoh1 deletion strongly confers pit cell stemness. ATOH1 depletion significantly accelerates cancer stemness and chemoresistance in Tff1-CreERT2; Rosa26Tdtomato and Tff1-CreERT2; Apcfl/fl ; p53fl/fl (TcPP) mouse models and organoids. ATOH1 deficiency downregulates growth arrest-specific protein 1 (GAS1) by suppressing GAS1 promoter transcription. GAS1 forms a complex with RET, which inhibits Tyr1062 phosphorylation, and consequently activates the RET/AKT/mTOR signaling pathway by ATOH1 deficiency. Combining chemotherapy with drugs targeting AKT/mTOR signaling can overcome ATOH1 deficiency-induced chemoresistance. Moreover, it is confirmed that abnormal DNA hypermethylation induces ATOH1 deficiency. Taken together, the results demonstrate that ATOH1 loss promotes cancer stemness through the ATOH1/GAS1/RET/AKT/mTOR signaling pathway in GAC, thus providing a potential therapeutic strategy for AKT/mTOR inhibitors in GAC patients with ATOH1 deficiency.

Microfluidic integrated D-shaped optical fiber SERS probe with high sensitivity and ability of multi-molecule detection.

In order to enhance the sensitivity, integration, and practical application capability of Raman detection systems, we propose a multi-channel microfluidic integrated D-shaped optical fiber SERS (Surface-enhanced Raman scattering) probe structure. Firstly, a microfluidic polydimethylsiloxane (PDMS) channel was fabricated using a self-designed multi-channel microfluidic template. Secondly, a uniform layer of silver nanoparticles was deposited on the D-shaped optical fiber using the liquid-liquid interface method. Finally, the D-shaped optical fiber was plasma-bonded to the multi-channel microfluidic channel and a cover glass, resulting in a microfluidic integrated D-shaped optical fiber SERS probe. The prepared sample exhibited excellent detection performance for R6G (rhodamine 6 G) with a detection limit as low as 10-11 mol/L and an enhancement factor of 1.14 × 109. Moreover, the multi-channel configuration enables simultaneous detection of multiple molecules, demonstrating excellent multi-channel multiplexing capability.

Optimal Frequency of Hepatitis C Virus (HCV) RNA Testing for Detection of Acute HCV Infection Among At-risk People With Human Immunodeficiency Virus: A Multicenter Study.

Using 3-stage pooled-plasma hepatitis C virus (HCV) RNA testing performed quarterly among at-risk people with human immunodeficiency virus (PWH), we found that if testing had been performed every 6 or 12 months, 58.6%-91.7% of PWH who recently acquired HCV would be delayed for diagnosis and might contribute to onward HCV transmission with longer durations.

Evolution of estimated glomerular filtration rate in HIV/HCV-coinfected patients who received direct-acting antivirals: A multicenter retrospective study.

BACKGROUND: The short-term impact of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) combined with antiretroviral therapy (ART) on renal function in patients with HIV/HCV-coinfection remains controversial. METHODS: This multicenter, retrospective study aimed to sequentially record the estimated glomerular filtration rate (eGFR) at baseline, end of therapy (EOT), 12 weeks off-treatment (SVR12), and at time points after SVR12 (post-SVR12) and to identify the factors associated with an eGFR decline to <60 ml/min/1.73 m2 in HIV/HCV-coinfected patients receiving DAAs. The evolution of mean eGFRs between different ART and DAAs combinations among patients of different HIV transmission routes were compared using a generalized linear mixed effects model. The periods between baseline and EOT, between EOT and post-SVR12, and between baseline and post-SVR12 were defined as the on-treatment, post-treatment, and all-course periods, respectively. Acute kidney disease (AKD) was defined as a decline of eGFR to <60 ml/min/1.73 m2. RESULT: A total of 445 patients with baseline eGFRs >60 ml/min/1.73 m2 were included. We found that eGFRs declined during the on-treatment period in the tenofovir-containing ART and SOF-based DAA groups. There were no differences in the slope coefficient during the on-treatment and post-treatment periods among all risk groups except for people who inject drug. Increasing age and plasma HIV RNA >20 copies/ml before DAA treatment were factors independently associated with AKD during the on-treatment period while increasing age was independently associated with AKD during the all-course period. CONCLUSION: Only increasing age was an independent factor associated with AKD among HIV/HCV-coinfected patients during and after DAA treatments.

Week 96 Results of Switching from Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide among HIV/Hepatitis B Virus-Coinfected Patients.

Data regarding the durability of tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) in maintaining hepatitis B virus (HBV) viral suppression among HIV/HBV-coinfected patients are limited. Between February and October 2018, 274 HIV/HBV-coinfected participants who had achieved HIV RNA of <50 copies/mL with tenofovir disoproxil fumarate (TDF)-containing ART and switched to elvitegravir/cobicistat/emtricitabine/TAF were prospectively enrolled. Serial plasma HIV and HBV viral loads, HBV and hepatitis D virus (HDV) serology, renal parameters, metabolic profiles, and bone mineral density (BMD) were assessed through 96 weeks. At baseline and weeks 48, 72, and 96, 5.8%, 5.1%, 5.8%, and 5.1% of the participants had plasma HBV DNA of ≥20 IU/mL, and 0%, 0.7%, 1.5%, and 2.2% had HIV RNA of ≥50 copies/mL, respectively. Hepatitis B surface antigen (HBsAg) loss occurred in 1.5% of 274 participants, and hepatitis B e-antigen (HBeAg) loss or seroconversion occurred in 14.3% of 35 HBeAg-positive participants. Compared with baseline, the median urine protein-to-creatinine ratio (79 versus 63 mg/g, P < 0.001) and ß2-microglobulin-to-creatinine ratio (165 versus 83 µg/g, P < 0.001) continued to decrease at week 96. BMD of the spine and hip slightly increased (mean change, +0.9% and +0.5%, respectively). The median triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol increased from baseline to week 96 (116 versus 141, 166 versus 190, 99 versus 117, and 42 versus 47 mg/dL, respectively; all P < 0.001), and most of the increases occurred in the first 48 weeks of the switch. Our study showed that switching from TDF-containing ART to elvitegravir/cobicistat/emtricitabine/TAF maintained HBV and HIV viral suppression through 96 weeks among HIV/HBV-coinfected patients. Proteinuria continued to improve, while fasting lipids increased and BMD stabilized at 96 weeks after the switch. IMPORTANCE Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide as a maintenance therapy showed durable and high rates of viral suppression for HIV/HBV-coinfected patients, with only 5.1% and 2.2% of patients having HBV DNA of ≥20 IU/mL and HIV RNA of ≥50 copies/mL, respectively, at 96 weeks. Our study fills the data gap on the long-term clinical effectiveness of tenofovir alafenamide-containing antiretroviral therapy in people living with HIV who have HBV coinfection.

The evolution of approach in the resuscitation of neonates born with meconium-stained amniotic fluid: a tale of two countries, China and U.S.A., in the past 60 years / 中国当代儿科杂志

Neonates born through meconium-stained amniotic fluid (MSAF) may develop complications including meconium aspiration syndrome, persistent pulmonary hypertension of newborn and death. The approach to the resuscitation of these neonates has significantly evolved for the past few decades. Initially, under direct visualization technique, neonates with MSAF were commonly suctioned below the vocal cords soon after delivery. Since 2015, Neonatal Resuscitation Program (NRP®) of the American Academy of Pediatrics has recommended against "routine" endotracheal suctioning of non-vigorous neonates with MSAF but favored immediate resuscitation with positive pressure ventilation via face-mask bagging. However, the China neonatal resuscitation 2021 guidelines continue to recommend routine endotracheal suctioning of non-vigorous neonates born with MSAF at birth. This review article discusses the differences and the rationales in the approach in the resuscitation of neonates with MSAF between Chinese and American NRP® guidelines over the past 60 years.

Preparation of 4-sulfonylcalix6arene-modified cotton for uranium contamination removal / 中国辐射卫生

Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.

Intervention effect of Tuina pressing and kneading the Huantiao (GB30) acupoint on NF-κB p65 protein at spinal cord dorsal horn in sciatica rats / 中国骨伤

OBJECTIVE@#To observe the analgesic effect of Tuina by pressing and kneading the Huantiao (GB30) acupoint on rats with chronic constriction injury (CCI) and to explore the analgesic mechanism of Tuina on sciatica rats.@*METHODS@#Thirty-two SPF male SD rats weighing 180 to 220 g were randomly divided into fore groups:blank group (without any treatment), sham group (only exposed without sciatic nerve ligating), model group (sciatic nerve ligating) and Tuina group (manual intervention after lsciatic nerve ligating). The CCI model was prepared by ligating the right sciatic nerve of the rats, on the third day of modeling, the rats in the Tuina group were given pressing and kneading the Huantiao (GB30) point for 14 days, and the changes of paw withdrawal threshold(PWT), paw withdrawal latency(PWL) were measured before and on the 1st, 3rd, 7th, 10th, 14th and 17th days after modeling. The changes of sciatic functional index(SFI) were measured before and on the 1st and 17th day after modeling. The morphological changes of the sciatic nerve were observed by hematoxylin-eosin(HE) staining;and the differences in NF-κB protein expression in the right dorsal horn of the spinal cord of rats were detected.@*RESULTS@#Following modeling, there was no significant difference in PWT, PWL and SFI between the blank group and the sham group (P>0.05), but the PWT, PWL and SFI of the model group and the Tuina group decreased significantly (P<0.01). After manual intervention, the pain threshold of rats in Tuina group increased. On the 8th day of manual intervention (the 10th day after modeling), PWT in Tuina group increased significantly compared with that in model group (P<0.01). On the 5th day of manual intervention (the 7th day after modeling), the PWL of the massage group was significantly higher than that of the model group (P<0.01). The pain threshold of rats in Tuina group continued to rise with the continuous manipulation intervention. After 14 days of manipulative intervention, the sciatic nerve function index of rats in the Tuina group increased significantly(P<0.01). Compared with the blank group and sham group, the myelinated nerve fibers of sciatic nerve in the model group were disordered and the density of axons and myelin sheath was uneven. Compared with the model group, the nerve fibers of rats in the Tuina group were gradually continuous and the axons and myelin sheath were more uniform than those in the model group. Compared with the blank group and sham group, the expression of NF-κB protein in the right spinal dorsal horn of the model group was significantly increased(P<0.01). Compared with the model group, the expression of NF-κB protein in the right spinal dorsal horn of rats in Tuina group decreased significantly(P<0.01).@*CONCLUSION@#Pressing and kneading the Huantiao (GB30) point restores nerve fiber alignment;and improves the PWT、PWL and SFI in the CCI model by decreasing NF-κB p65 protein expression in the spinal dorsal horn. There fore, Tuina demmstrates an analgesic effect and improves the gait of rats with sciatica.

Diagnosis and treatment of malignant mesothelioma of the tunica vaginalis testis: a series of 7 cases / 中华外科杂志

Objective: To investigate the clinical features, diagnosis, prognosis of malignant mesothelioma of the tunica vaginalis testis (MMTVT). Methods: The clinicopathological data of 7 patients with MMTVT who treated at Sun Yat-sen University Cancer Center between January 2010 and October 2022 were retrospectively reviewed. Cases were first diagnosed at (M (IQR)) 49 (23) years old (range: 27 to 64 years old). The main clinical manifestations were scrotal enlargement (7 cases) and hydrocele (2 cases). Results: Three patients underwent radical orchiectomy as initial treatment, 2 cases underwent hydrocelectomy due to diagnosis of hydrocele, followed by radical orchiectomy at Sun Yat-sen University Cancer Center, and 2 cases underwent transscrotal orchiectomy. Common tumor markers of testicular cancer were not significantly elevated in MMTVT. The expression of tumor PD-L1 was positive in 2 out of the 3 cases. One patient received adjuvant chemotherapy and 2 patients received first-line chemotherapy after tumor recurrence. Chemotherapy regimens used include cisplatin+pemetrexed. Up to October 2022, 3 cases relapsed, of which 2 cases died. The median overall survival was 35 months (range: 4 to 87 months) and the median progression-free survival was 6 months (range: 2 to 87 months). Conclusions: MMTVT at early stage should be treated with early radical orchiectomy and followed up closely after surgery. The cisplatin+pemetrexed regimen is a common option for the treatment of metastatic MMTVT, while whether immune checkpoint inhibitors could serve as a second-line treatment option deserves further research.

The effect of SIRT3 on lung cancer cell apoptosis by regulating ROS-mediated oxidative stress under hypoxic conditions / 安徽医科大学学报

Objective To investigate the effect of sirtuin 3(SIRT3)on the oxidative stress response and hypoxia inducible factor-1α(HIF-1α)expression in lung cancer cells through reactive oxygen species(ROS)under hypoxic conditions and its mechanism.Methods Human non-small cell lung cancer A549 cells were exposed to hypoxia for 0 h,12 h,24 h and 48 h.The mRNA and protein expressions of HIF-1α and SIRT3 were detected by RT-PCR and Western blot to determine the optimal time of hypoxia induction.A549 cells were divided into 5 groups:control group,hypoxia group,hypoxia+ROS inhibitor n-acetylcysteine(NAC)group,hypoxia+(SIRT3 overexpression)SIRT3-OE group and hypoxia+SIRT3-OE+NAC group.Cell proliferation was detected by MTT assay.Cell apop-tosis was detected by flow cytometry.The mRNA and protein expressions of HIF-1 α and SIRT3 in each group were detected by RT-PCR and Western blot.ROS content in each group was detected by flow cytometry.The contents of malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in the cells of each group were detected by biochemical kits.Results The optimal induction time of hypoxia was 24 h.Compared with the control group,the apoptosis rate,SIRT3 mRNA and protein levels,SOD and GSH contents in the hypoxia group signifi-cantly decreased(P＜0.01),the cell proliferation ability,HIF-1 α mRNA and protein levels,ROS and MDA con-tent in cells significantly increased(P＜0.01).Compared with the hypoxia group,the apoptosis rate,SIRT3 mR-NA and protein levels,SOD and GSH contents in the hypoxia+NAC and hypoxia+SIRT3-OE groups increased(P＜0.05),the cell proliferation ability,HIF-1 α mRNA and protein levels,ROS and MDA content in cells de-creased(P＜0.05).Compared with the hypoxia+NAC group,the apoptosis rate,SIRT3 mRNA and protein lev-els,SOD and GSH contents in the hypoxia+SIRT3-OE+NAC group significantly increased(P＜0.01),the cell proliferation ability,HIF-1 α mRNA and protein levels,ROS and MDA content in cells significantly decreased(P＜0.01).Conclusion Under hypoxic conditions,SIRT3 can promote cell apoptosis and inhibit lung cancer pro-gression by mediating ROS to inhibit oxidative stress response and HIF-1 α expression in lung cancer cells.

Significance of white blood cells count, C-reactive protein and procalcitonin for the detection of infectious complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy / 国际外科学杂志

Objective:To investigate the risk factors for infection after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+ HIPEC), and observe the infection in patients who underwent this combined procedure, to explore the predictive value of postoperative white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT) and systemic immune inflammation index (SII) for postoperative infection.Methods:Clinical data of 106 patients who underwent CRS + HIPEC in the Fifth Medical Clinical College of Shanxi Medical University between July 2019 and July 2022 were retrospectively analyzed. These patients, including 61 males and 45 females, (58.93±10.65) years old, were divided into the infection group ( n=19) and the non-infection group ( n=87) according to the presence of postoperative infection. Risk factors were analyzed for patients in the infection group, and postoperative WBC, CRP, PCT and SII were determined for patients in both groups to determine their prognostic values. Risk factors for postoperative secondary infection in patients with CRS+ HIPEC were analyzed using univariate and multivariate logistic regression. Predictive values of WBC, PCT, CRP and SII for postoperative infection were evaluated by receiver operating characteristic (ROC) curve, and the optimal cutoff values of these variables were determined by Youden index and evaluated using sensitivity, specificity, positive predictive value, and negative predictive value as evaluation indexes. Nomogram prediction model was constructed using R software and samples were included in this model to calculate the total score of these patients. ROC curve analysis and calibration curve verification were then performed. Results:Univariate analysis showed significant differences in age, body mass index (BMI), postoperative fistulization, preoperative serum albumin, combined multiple organ resection, and operation duration between the infection and non-infection groups ( P<0.05). WBC, CRP, PCT and SII were compared between the infection group and the non-infection group on were compared on postoperative days 1, 3, 5 and 7, and the ROC curves were plotted accordingly. The area under the ROC curve (AUC) of the WBC, CRP, PCT and SII on postoperative Days 1, 3, 5 and 7, and their 95% CI, sensitivities and specificities were compared. It was found that the predictive values of the 5th postoperative day WBC and PCT, and the 7th postoperative day CRP were superior to those determined on other postoperative days, and SII was not significant in predicting postoperative secondary infection in patients who underwent CRS+ HIPEC. The cut-off values of the 5th postoperative day WBC and PCT and the 7th postoperative day CRP were 7.7×10 9/L, 2.068 ng/mL and 76.43 mg/L, respectively, and AUCs and their 95% CI were 0.754 and (0.625, 0.883), 0.830 and (0.717, 0.943), 0.715 and (0.584, 0.846), respectively, with sensitivities of 78.9%, 68.4% and 63.2%, respectively, and specificities of 70.1%, 96.5% and 75.9%, respectively. The predictive values of PCT on postoperative days 1, 3, 5 and 7 were superior to those of WBC, CRP and SII determined on each corresponding day. The cut-off values of the 5th postoperative day WBC and PCT and the 7th postoperative day CRP were used as the classification thresholds, and the results after classification as well as significant variables in univariate analysis, including age, BMI≥25 kg/m 2, postoperative fistulization, preoperative serum albumin≥35 g/L, number of organs resected and operation duration were included in multivariate logistic regression analysis. The results showed that BMI≥25 kg/m 2, combined multiple organ resection, WBC and PCT on the 5th postoperative day and, CRP on the 7th postoperative day were independent risk factors for secondary infection ( P<0.05). A Nomogram prediction model was then constructed. Points indicated the scores for each variable, and the corresponding scores were 70 when BMI was ≥25 kg/m 2, 80 when multiple organ resection was combined, 100 when the 5th postoperative day WBC was ≥7.7×10 9/L, and 79 when the 7th postoperative day CRP was ≥76.3. The sum of the scores for all variable was calculated and used as total score for the patient. The total score obtained from the Nomogram prediction model was used for ROC curve analysis and calibration curve verification. The ROC curve analysis showed that the AUC was 0.966, with a sensitivity of 0.895 and specificity of 0.966, indicating an excellent discriminative power of the model. The significance level of the calibration curve was 0.05, and the absolute error between the predicted and actual incidences of postoperative infection after CRS+ HIPEC was 0.038. Conclusions:The incidence of secondary infection after CRS+ HIPEC is related to factors such as BMI and combined multiple organ resection. Inflammation markers in peripheral blood, including PCT, CRP and WBC, can serve as predictors for postoperative secondary infection in patients with CRS+ HIPEC, and the fifth postoperative day WBC and PCT and the seventh postoperative day CRP among others have the highest diagnostic values for postoperative infections. In addition, the predictive value of combined diagnosis is superior to that of individual testing.

Switching to coformulated bictegravir, emtricitabine, and tenofovir alafenamide maintained viral suppression in adults with historical virological failures and K65N/R mutation.

OBJECTIVES: Real-world experience with coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is sparse as a switch regimen among people living with HIV (PLWH) having achieved viral suppression after previous virologic failures with the emergence of K65N/R. METHODS: In this retrospective study, PLWH aged ≥20 years who had previous virologic failures with emergent K65N/R were included for switching to BIC/FTC/TAF after having achieved plasma HIV RNA load (PVL) <200 copies/ml for ≥3 months. PLWH were excluded if integrase inhibitor resistance-associated mutations were detected. The primary end point was losing virologic control (PVL >50 copies/ml) at week 48 using a modified US Food and Drug Administration snapshot algorithm. RESULTS: A total of 72 PLWH with K65N/R who switched to BIC/FTC/TAF were identified. A total of 42 (59.7%) had concurrent M184V/I, and 9 (12.5%) had ≥1 thymidine analog mutations. The median duration of viral suppression was 4.7 years (interquartile range 2.3-5.8), and 97.2% (n = 70) had PVL <50 copies/ml before switching. After a median observation of 98.6 weeks (interquartile range 77.9-120.3), 94.4% (n = 68) continued BIC/FTC/TAF. At week 48, the rate of losing virologic control was 2.8% (2/72). M184V/I was not associated with viral rebound. CONCLUSION: Despite the emergence of K65N/R +/- M184V/I after virologic failures, BIC/FTC/TAF could be an option for simplification after viral suppression.

Research progress of hyperthermic intraperitoneal chemotherapy in the treatment of colorectal cancer / 国际外科学杂志

Colorectal cancer is a common digestive system malignant tumor in the world, its incidence and mortality rate is in the forefront, with the social progress and the change of diet structure, the incidence of colorectal cancer is gradually increasing, and there is a trend of younger age. Among them, peritoneal metastasis is the main cause of death in patients with colorectal cancer. Non-surgical treatment has been used in the past, but the prognosis is poor. How to treat and prevent peritoneal metastasis in colorectal cancer patients and improve the prognosis of such patients as much as possible is a question worth our in-depth study. The hyperthermic intraperitoneal chemotherapy provides a new direction for the treatment of colorectal cancer patients, usually combined with surgical treatment, and co-applied in the clinic as a new treatment model. This article reviews the treatment mode of hyperthermic intraperitoneal chemotherapy, the choice of drugs, and the progress of research in the treatment and prevention of peritoneal metastasis in colorectal cancer.