Lipoprotein(a) is associated with recurrent cardiovascular events in patients with coronary artery disease and prediabetes or diabetes.

PURPOSE: Elevated lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are both associated with adverse events in high-risk patients with established coronary artery disease (CAD). Currently, the association between Lp(a) levels and recurrent cardiovascular (CV) events (CVEs) remained undetermined in patients with different glucose status. Therefore, this study aimed to investigate the prognostic significance of Lp(a) levels for recurrent CVEs in high-risk CAD patients who suffered from first CVEs according to different glycemic metabolism. METHODS: We recruited 5257 consecutive patients with prior CVEs and followed up for recurrent CVEs, including CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. Patients were assigned to low, medium, and high groups according to Lp(a) levels and further stratified by glucose status. RESULTS: During a median 37-month follow-up, 225 (4.28%) recurrent CVEs occurred. High Lp(a) was independently associated with recurrent CVEs [adjusted Hazard Ratio (HR), 1.57; 95% confidence interval (CI) 1.12-2.19; P = 0.008]. When participants were classified according to Lp(a) levels and glycemic status, high Lp(a) levels were associated with an increased risk of recurrent CVEs in pre-DM (adjusted HR, 2.96; 95% CI 1.24-7.05; P = 0.014). Meanwhile, medium and high Lp(a) levels were both associated with an increased risk for recurrent CVEs in DM (adjusted HR, 3.09; 95% CI 1.30-7.34; P = 0.010 and adjusted HR, 3.13, 95% CI 1.30-7.53; P = 0.011, respectively). CONCLUSIONS: This study demonstrated that elevated Lp(a) levels were associated with an increased recurrent CVE risk in patients with CAD, particularly among those with pre-DM and DM, indicating that Lp(a) may provide incremental value in risk stratification in this population.

Kidney Transplant Clinicians' Perceptions of Palliative Care for Patients With Failing Allografts in the US: A Mixed Methods Study.

RATIONALE & OBJECTIVE: Kidney transplant patients with failing allografts have a physical and psychological symptom burden as well as high morbidity and mortality. Palliative care is underutilized in this vulnerable population. We described kidney transplant clinicians' perceptions of palliative care to delineate their perceived barriers to and facilitators of providing palliative care to this population. STUDY DESIGN: National explanatory sequential mixed methods study including an online survey and semistructured interviews. SETTING & PARTICIPANTS: Kidney transplant clinicians in the United States surveyed and interviewed from October 2021 to March 2022. ANALYTICAL APPROACH: Descriptive summary of survey responses, thematic analysis of qualitative interviews, and mixed methods integration of data. RESULTS: A total of 149 clinicians completed the survey, and 19 completed the subsequent interviews. Over 90% of respondents agreed that palliative care can be helpful for patients with a failing kidney allograft. However, 46% of respondents disagreed that all patients with failing allografts benefit from palliative care, and two-thirds thought that patients would not want serious illness conversations. More than 90% of clinicians expressed concern that transplant patients and caregivers would feel scared or anxious if offered palliative care. The interviews identified three main themes: (1) transplant clinicians' unique sense of personal and professional responsibility was a barrier to palliative care engagement, (2) clinicians' uncertainty regarding the timing of palliative care collaboration would lead to delayed referral, and (3) clinicians felt challenged by factors related to patients' cultural backgrounds and identities, such as language differences. Many comments reflected an unfamiliarity with the broad scope of palliative care beyond end-of-life care. LIMITATIONS: Potential selection bias. CONCLUSIONS: Our study suggests that multiple barriers related to patients, clinicians, health systems, and health policies may pose challenges to the delivery of palliative care for patients with failing kidney transplants. This study illustrates the urgent need for ongoing efforts to optimize palliative care delivery models dedicated to kidney transplant patients, their families, and the clinicians who serve them. PLAIN-LANGUAGE SUMMARY: Kidney transplant patients experience physical and psychological suffering in the context of their illnesses that may be amenable to palliative care. However, palliative care is often underutilized in this population. In this mixed-methods study, we surveyed 149 clinicians across the United States, and 19 of them completed semistructured interviews. Our study results demonstrate that several patient, clinician, system, and policy factors need to be addressed to improve palliative care delivery to this vulnerable population.

[Precise minimally invasive treatment of mandibular fracture in children assisted by digital surgery technology].

Objective: To explore the role of digital three-dimensional printing technology and multifunctional board in the treatment of mandibular fracture in children. Methods: From January 2006 to January 2022, 42 children with mandibular fracture were treated by Department of Stomatology, in The First Affiliated Hospital of Bengbu Medical College, including 25 males and 17 females. The patients, aged from 4 to 12 years, with the median age was 10 years old, were divided into observation group (22 cases) and routine group (20 cases) according to the treatment methods. In the observation group, the multifunctional board was made before operation, and the CT data of the children were imported into Mimics software in".dicom"format, and the displaced mandible was virtually reset. The jaw reduction model was made by three-dimensional printing, and the surgical operation was simulated on the reduction model to determine the model and position of the internal fixation device and shape it. During the operation, the fracture was reduced and fixed according to the preoperative design; The conventional group was treated with open reduction and internal fixation of mandibular fracture by traditional methods, and the clinical application value was compared and analyzed through the intraoperative situation, occlusal relationship, and follow-up of the two groups. Results: The total intraoperative bleeding volume [(30.25±4.02) ml] and surgical time [(64.3±9.2) min] in the observation group were significantly lower than those in the conventional group [(35.13±5.69) ml and (84.6±13.9) min, respectively] (F=6.18, P=0.003; F=1.32, P=0.001). The excellent and good rate of occlusal relationship in the observation group [96% (21/22)] was significantly higher than that in the conventional group [85% (17/20)] (F=4.27, P=0.039). The incidence of complications, the observation group, 1 case of poor occlusion, 1 case of postoperative infection; In the routine group, there were 3 cases with poor occlusion, 1 case with nerve injury, 1 case with root injury and 1 case with tooth germ injury. Conclusions: The application of digitization three-dimensional printing technology combined with multifunctional occlusal plate in children's mandibular fracture is minimally invasive, safe, efficient and accurate, and the clinical effect is good.

Physical Properties and Clinical Performance of Short Fiber Reinforced Resin-based Composite in Posterior Dentition: Systematic Review and Meta-analysis.

OBJECTIVE: This study compares the physical properties and clinical performance of short fiber reinforced composites (SFRC) to those of particulate-filled resin-based composites (PFRC) for class I and II direct restorations in permanent dentition. METHODS: Systematic review and meta-analysis was conducted using PubMed, Embase (Elsevier), and Dentistry and Oral Sciences Source (EBSCO) databases. The outcomes evaluated were physical properties including flexural strength, flexural modulus, elastic modulus, microhardness, shrinkage, fracture toughness, degree of conversion, and depth of cure. Clinical performance was evaluated with a systematic review. RESULTS: The meta-analyses favored SFRC for flexural strength and fracture toughness compared to every PFRC subgroup, with a high quality of evidence. For all other properties, the meta-analyses favored SFRC to overall PFRC, with some non-significant differences with certain PFRC subgroups. The most recent clinical trial showed SFRC performed similarly to PFRC, however older studies suggest inferior surface texture and discoloration of SFRC compared to PFRC. CONCLUSION: This study can aid dental professionals in clinical decision making, supporting that SFRC offers improved physical properties, especially fracture resistance and flexural strength, compared to PFRC.

The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.

BACKGROUND: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). METHODS: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). RESULTS: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. PROTOCOL REGISTRATION: PROSPERO (CRD42021277495) on the 25th of October 2021.

The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants.

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was considered less of a concern. For the initial approach to immunosuppression reduction, 60% stop antimetabolites first, and 26% defer to the transplant nephrologist. Communicating with transplant centers about immunosuppression cessation was reported to occur always by 60%, and sometimes by 29%, while 12% reported making the decision independently. Nephrologists with academic appointments communicate with transplant providers more than private nephrologists (74% vs. 49%, p = 0.015). There are heterogeneous approaches to the care of patients with a failing allograft. Efforts to strengthen transitions of care and to develop practical practice guidelines are needed to improve the outcomes of this vulnerable population.

Efficient Spin-to-Charge Conversion via Altermagnetic Spin Splitting Effect in Antiferromagnet RuO_{2}.

The relativistic spin Hall effect and inverse spin Hall effect enable the efficient generation and detection of spin current. Recently, a nonrelativistic altermagnetic spin splitting effect (ASSE) has been theoretically and experimentally reported to generate time-reversal-odd spin current with controllable spin polarization in antiferromagnet RuO_{2}. The inverse effect, electrical detection of spin current via ASSE, still remains elusive. Here we show the spin-to-charge conversion stemming from ASSE in RuO_{2} by the spin Seebeck effect measurements. Unconventionally, the spin Seebeck voltage can be detected even when the injected spin current is polarized along the directions of either the voltage channel or the thermal gradient, indicating the successful conversion of x- and z-spin polarizations into the charge current. The crystal axes-dependent conversion efficiency further demonstrates that the nontrivial spin-to-charge conversion in RuO_{2} is ascribed to ASSE, which is distinct from the magnetic or antiferromagnetic inverse spin Hall effects. Our finding not only advances the emerging research landscape of altermagnetism, but also provides a promising pathway for the spin detection.

Evidence for Band Renormalizations in Strong-Coupling Superconducting Alkali-Fulleride Films.

There has been a long-standing debate about the mechanism of the unusual superconductivity in alkali-intercalated fullerides. In this Letter, using high-resolution angle-resolved photoemission spectroscopy, we systematically investigate the electronic structures of superconducting K_{3}C_{60} thin films. We observe a dispersive energy band crossing the Fermi level with the occupied bandwidth of about 130 meV. The measured band structure shows prominent quasiparticle kinks and a replica band involving the Jahn-Teller active phonon modes, which reflects strong electron-phonon coupling in the system. The electron-phonon coupling constant is estimated to be about 1.2, which dominates the quasiparticle mass renormalization. Moreover, we observe an isotropic nodeless superconducting gap beyond the mean-field estimation (2Δ/k_{B}T_{c}≈5). Both the large electron-phonon coupling constant and large reduced superconducting gap suggest a strong-coupling superconductivity in K_{3}C_{60}, while the electronic correlation effect is suggested by the observation of a waterfall-like band dispersion and the small bandwidth compared with the effective Coulomb interaction. Our results not only directly visualize the crucial band structure but also provide important insights into the mechanism of the unusual superconductivity of fulleride compounds.

No causal effects between rosiglitazone and cardiovascular disease or risk factors: a Mendelian randomization study.

OBJECTIVE: Although many observational studies have shown an association between rosiglitazone and cardiovascular disease (CVD) or risk factors, controversy remains. We conducted a Mendelian randomized (MR) study to explore whether rosiglitazone is causally related to CVDs and risk factors. PATIENTS AND METHODS: Single-nucleotide polymorphisms associated with rosiglitazone at genome-wide significance were identified from a genome-wide association study of 337,159 European-ancestry individuals. Four treatments with rosiglitazone-associated single-nucleotide polymorphisms associated with a higher risk of CVDs were used as an instrumental variable (IV). Summary-level data for 7 CVDs and 7 risk factors were obtained from UK Biobank and consortia. RESULTS: We found no causal effects of rosiglitazone, either on CVDs or risk factors. The results were consistent in sensitivity analyses using Cochran's Q test, MR-PRESSO method, leave-one-out analysis and Mendelian randomization-Egger method (MR-Egger), and no directional pleiotropy was observed. Sensitivity analyses confirmed that rosiglitazone was not significantly associated with CVDs and risk factors. CONCLUSIONS: The findings from this MR study indicate no causal relationship between rosiglitazone and CVDs or risk factors. Hence, previous observational studies may have been biased.

[Network meta-analysis comparing the clinical outcomes and safety of robotic, laparoscopic, and transanal total rectal mesenteric resection for rectal cancer].

Objective: To methodically assess the clinical effectiveness and safety of robot-assisted total rectal mesenteric resection (RTME), laparoscopic-assisted total rectal mesenteric resection (laTME), and transanal total rectal mesenteric resection (taTME). Methods: A computer search was conducted on PubMed, Embase, Cochrane Library, and Ovid databases to identify English-language reports published between January 2017 and January 2022 that compared the clinical efficacy of the three surgical procedures of RTME, laTME, and taTME. The quality of the studies was evaluated using the NOS and JADAD scales for retrospective cohort studies and randomized controlled trials, respectively. Direct meta-analysis and reticulated meta-analysis were performed using Review Manager software and R software, respectively. Results: Twenty-nine publications comprising 8,339 patients with rectal cancer were ultimately included. The direct meta-analysis indicated that the length of hospital stay was longer after RTME than after taTME, whereas according to the reticulated meta-analysis the length of hospital stay was shorter after taTME than after laTME (MD=-0.86, 95%CI: -1.70 to -0.096, P=0.036). Moreover, the incidence of anastomotic leak was lower after taTME than after RTME (OR=0.60, 95%CI: 0.39 to 0.91, P=0.018). The incidence of intestinal obstruction was also lower after taTME than after RTME (OR=0.55, 95%CI: 0.31 to 0.94, P=0.037). All of these differences were statistically significant (all P<0.05). There were no statistically significant differences between the three surgical procedures regarding the number of lymph nodes cleared, length of the inferior rectal margin, or rate of positive circumferential margins (all P>0.05). An inconsistency test using nodal analysis revealed no statistically significant differences between the results of direct and indirect comparisons of the six outcome indicators (all P>0.05). Furthermore, we detected no significant overall inconsistency between direct and indirect evidence. Conclusion: taTME has advantages over RTME and laTME, in terms of radical and surgical short-term outcomes in patients with rectal cancer.

B cell and antibody targeting of transplant alloantigen epitopes is supported by both self and allo-recognition.

Donor-specific antibody (DSA) responses against human leukocyte antigen (HLA) proteins mismatched between kidney transplant donors and recipients cause allograft loss. Using single-cell, molecular, structural, and proteomic techniques, we profiled the HLA-specific (alloreactive) B cell response in kidney and blood of a transplant recipient with antibody-mediated rejection (AMR). We identified 14 distinct alloreactive B cell lineages, which spanned the rejected organ and blood and expressed high-affinity anti-donor HLA-specific B cell receptors, many of which were clonally linked to circulating DSA. The alloreactive B cell response was focused on exposed, solvent-accessible mismatched HLA residues, while also demonstrating extensive contacts with self-HLA residues. Consistent with structural evidence of self-recognition, measurable self-reactivity by donor-specific B cells was common and positively correlated with anti-donor affinity maturation. Thus, allo- and self-reactive signatures appeared to converge, suggesting that during AMR, the recognition of non-self and breaches of tolerance conspire to produce a pathogenic donor-specific adaptive response.

[Analysis of brain volume asymmetry and clinical application in patients with temporal lobe epilepsy with hippocampal sclerosis based on automatic brain segmentation].

Objective: To analyze whole brain structural volume asymmetry in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) using automated brain segmentation technology, and to investigate the application value of this technology in the diagnosis of TLE-HS and the performance in determining the location the lateralization of epileptogenic focus. Methods: Twenty-eight patients with TLE-HS were enrolled in the First Affiliated Hospital of Zhengzhou University from April 2019 to October 2020, including 13 females and 15 males, aged ranged from 18 to 63 (30±12) years, and these patients were divided two group according to the epilepsy lateralization, left TLE-HS(LTLE-HS) group (n=11), right TLE-HS(RTLE-HS) group (n=17) and 28 normal controls [aged ranged from 18 to 49 (29±10) years]. All of these subjects underwent three-dimensional T1 weighted image (3D T1WI). The differences of brain structure and volumes in LTLE-HS, RTLE-HS and normal controls group were retrospectively analyzed, and Pearson's correlation coefficient was used to evaluate the left and right volume correlations, and effect size was used for evaluating the differences in left and right volume averages. The asymmetry index (AI) of the left and right lateral volumes in each group was also calculated and compared among the three groups. Results: Standard volumes of all structures within the brain were asymmetric in the normal controls, LTLE-HS, and RTLE-HS groups, with smaller volumes of ipsilateral hippocampus than contralateral hippocampus in both the LTLE-HS and RTLE-HS groups(0.20%±0.03% vs 0.24%±0.02%,0.21%±0.03% vs 0.25%±0.02% respectively;both P<0.001), and smaller volumes of gray and white matter of the ipsilateral temporal lobe than contralateral in the LTLE-HS group(4.41%±0.38% vs 5.01%±0.43%,1.83%±0.22 % vs 2.22%±0.14%;both P<0.001). There was a moderate to strong linear correlation (0.553

Insomnia and multiple health outcomes: umbrella review of meta-analyses of prospective cohort studies.

OBJECTIVES: To evaluate existing evidence of prospective cohort studies on associations between insomnia and multiple health outcomes. STUDY DESIGN: An umbrella review of meta-analyses of prospective cohort studies. METHODS: A systematic search was undertaken in Pubmed, Embase, Cochrane, and Web of Science from inception to October 2021 to find meta-analyses of prospective cohort studies investigating the association of insomnia with any health outcome. The summary relative risk (SRR) for each meta-analysis was recalculated with random-effects model. The methodological quality and the quality of evidence were assessed by the A Measurement Tool to Assess Systematic Reviews and Grading of Recommendations, Assessment, Development and Evaluation, respectively. RESULTS: A total of 25 published meta-analyses of prospective cohort studies, reporting 63 SRRs for 29 unique outcomes were included. Insomnia was mainly related to cardiovascular outcomes and mental disorders. The former comprised atrial fibrillation (SRR: 1.30, 95% confidence interval: 1.26 to 1.35), cardiovascular diseases (1.45, 1.29 to 1.64), coronary heart disease (1.28, 1.10 to 1.50), myocardial infarction (1.42, 1.17 to 1.72), and stroke (1.55, 1.39 to 1.72). The latter involved alcohol abuse (1.35, 1.08 to 1.67), all mental disorders (2.16, 1.70 to 3.97), anxiety (3.23, 1.52 to 6.85), depression (2.31, 1.90 to 2.81), suicidal ideation (2.26, 1.79 to 2.86), suicidal attempt (1.99, 1.31 to 3.02), and suicidal death (1.72, 1.42 to 2.08). Besides, insomnia enhanced the risk of Alzheimer's disease (1.51, 1.06 to 2.14) and hyperlipidemia (1.64, 1.53 to 1.76). CONCLUSION: Insomnia exhibits considerable adverse outcomes, primarily comprises cardiovascular outcomes and mental disorders, but further studies with robustly designed trials are needed to draw firmer conclusions.

[Infection of human papillomavirus and head and neck cancer].

High-risk human papillomavirus (HPV)-related cancers consist of cervical cancer, anal cancer, penile cancer, vulvar cancer, vaginal cancer, and head and neck cancer (HNC). Of these, the disease burden of HNC is second only to cervical cancer. HNC mostly originates from malignant lesions of squamous epithelial cells and mainly includes oral cavity cancer, pharyngeal cancer (including nasopharyngeal cancer, oropharyngeal cancer, and hypopharyngeal cancer), and laryngeal cancer. Tobacco use, alcohol abuse, and HPV infection are three primary risk factors. Recently, there is an upward trend of HNC incidence globally, especially in high-income countries. In China, the disease burden and trends of HPV-related HNC are still not clear. A few small sample size and single-center studies suggest a high HPV prevalence and increasing trend in HNC. Methodological differences in HPV testing and regional variabilities still exist among these studies. Among the anatomic sites, oropharyngeal cancer has been shown to be caused by HPV infection, but the association of HPV with other sites is still under debate. In addition, there is a paucity of relevant studies. Here, this review narrates the association between HPV infection and HNC, compares the differences between global and Chinese studies, and then explores the importance of HPV infection in various anatomical sites. The main objective is to highlight the research on HPV-related HNC and promote relevant prevention and treatment programs.

Increased Sparc release from subchondral osteoblasts promotes articular chondrocyte degeneration under estrogen withdrawal.

OBJECTIVE: The incidence of osteoarthritis (OA) in menopausal women is significantly higher than in same-aged men. Investigating the role of subchondral osteoblasts in estrogen deficiency-induced OA may help elucidate the pathological mechanism, providing new insights for the diagnosis and treatment of menopausal OA. METHODS: A classical ovariectomy-induced OA (OVX-OA) rat model was utilized to isolate primary articular chondrocytes and subchondral osteoblasts, which were identified and then cocultured in Transwell. The expression of chondrocyte anabolic and catabolic indicators was evaluated. The differentially expressed proteins in the conditioned medium (CM) of osteoblasts were identified by Liquid Chromatograph-Mass Spectrometer (LC-MS/MS). Normal chondrocytes were treated with osteoblast CM, and then RNA sequencing was performed on the treated chondrocytes. KEGG was used to identify significant enrichment of signaling pathways, and Simple Western was used to verify the expression of related proteins in the signaling pathways. RESULTS: Coculture of OVX-OA subchondral osteoblasts with chondrocytes significantly downregulated the expression of the anabolic indicators and upregulated the expression of the catabolic indicators in chondrocytes. 1,601 proteins were identified in both normal and OVX osteoblast culture supernatants. Protein-protein interaction network analysis revealed that Sparc was one of the hub proteins. The AMPK/Foxo3a signaling pathway of chondrocytes was downregulated by OVX-OA osteoblasts CM. AICAR, the AMPK agonist, partially reversed the catabolic effect of OVX-OA osteoblasts on chondrocytes. CONCLUSIONS: Sparc secreted by OVX-OA subchondral osteoblasts can downregulate the AMPK/Foxo3a signaling pathway of chondrocytes, thereby promoting chondrocyte degeneration.

[Synergistic effect of azacitidine with homoharringtonine by activating the c-MYC/DDIT3/PUMA axis in acute myeloid leukemia].

Objective: This study aimed to explore the synergistic effect and underlying mechanism of azacitidine (AZA) in combination with homoharringtonine (HHT) in acute myeloid leukemia (AML) . Methods: The synergistic effects of AZA and HHT were examined by cell proliferation, apoptosis, and colony formation assays. The synergistic effects were calculated using the combination index (CI) , and the underlying mechanisms were explored using RNA sequencing, pathway inhibitors, and gene knockdown approaches. Results: Compared with the single-drug controls, AZA and HHT combination significantly induced cell proliferation arrest and showed a synergistic effect with CI < 0.9 in AML cells. In the combination group versus the single-drug controls, colony formation was significantly decreased, whereas apoptosis was significantly increased in U937 (P<0.001) and MV4-11 (P<0.001) cells. AZA and HHT combination activated the integrated stress response (ISR) signaling pathway and induced DDIT3-PUMA-dependent apoptosis in cells. Furthermore, it remarkably downregulated the expression of c-MYC. The combination also activated c-MYC/DDIT3/PUMA-mediated ISR signaling to induce synergy on apoptosis. The synergy of AZA+HHT on apoptosis was induced by activating c-MYC/DDIT3/PUMA-mediated ISR signaling. Conclusion: The combination of AZA and HHT exerts synergistic anti-AML effects by inhibiting cellular proliferation and promoting apoptosis through activation of the ISR signaling pathway via the c-MYC/DDIT3/PUMA axis.

[Overview of risk factors for stress urinary incontinence and strategies in its prevention and treatment].

Stress urinary incontinence is a medical problem that afflicts women worldwide. The causes can be mainly divided into 4 parts: increased abdominal pressure and chronic ischemia of pelvic floor muscles, endocrine changes, pelvic structural damages, inflammatory and consumptive states. The choice of prevention and treatment should also be based on a comprehensive assessment of individualized factors. Treatment techniques which are more minimally invasive or even non-invasive than surgery are currently a hot topic of research in the field of pelvic floor and urinary control, including laser and radiofrequency therapy, periurethral injection therapy, exogenous stem cell therapy and technology for activation of endogenous stem cells. They are expected to solve the clinical problem of stress urinary incontinence with a wider scope of application, lower trauma and fewer complications in the future.

[Effects of pretreatment HIV drug resistance on the virological response of HIV-infected patients after 3-year antiretroviral therapy].

Objective: To investigate the impact of pretreatment drug resistance (PDR) on virological effect among HIV-infected patients having received antiretroviral therapy (ART) after three years. Methods: The baseline survey of PDR among HIV-infected patients was conducted in 2018, with a three-year follow up study. The clinic data and virological laboratory test variables were statistically analyzed. Results: Of the 2 433 participants, 41.6% (1 012/2 433) were aged between 18 and 34, 82.8% (2 015/2 433) were males, 46.9% (1 142/2 433) had education of high school or above, 22.4% (544/2 433) were farmers, 33.8% (823/2 433) were unmarried, 48.1% (1 169/2 433) were infected heterosexually and 41.3% (1 004/2 433) were with CRF07_BC. The prevalence of PDR was 4.5% (109/2 433). The prevalence of virological suppression failure (viral load ≥50 copies/ml) and drug resistance at three years follow up after ART was 8.1%(196/2 433) and 2.5%(60/2 433) respectively. The prevalence of virological suppression failure and drug resistance at three years follow up after ART were 18.3% (20/109) and 7.6% (176/2 324), and 4.6% (5/109) and 2.4% (55/2 324) among participants with PDR and non-PDR, respectively. The results of multivariate logistic regression model showed that illiteracy (aOR=3.26, 95%CI: 1.82-5.86), primary and junior high school education (aOR=1.54, 95%CI: 1.09-2.18), CD4+T lymphocyte count <200/µl (aOR=2.77, 95%CI: 1.75-4.37) and CD4+T lymphocyte count 200-499/µl (aOR=1.55, 95%CI: 1.10-2.18) at a three year follow up visit after ART, missed drugs in the past month (aOR=4.24, 95%CI: 2.92-6.17), and PDR (aOR=2.84, 95%CI: 1.67-4.85) were statistically significant with virological suppression failure on treatment. Conclusions: The prevalence of PDR in China at a low level currently, and the virological suppression failure rate is low after three years of ART. It is necessary to strengthen drug resistance monitoring of HIV-infected patients and pay attention to the influence of PDR on treatment effect.