Targeting BIRC5 as a Therapeutic Approach to Overcome ASXL1-associated Decitabine Resistance.

Hypomethylating agents (HMAs) are widely employed in the treatment of myeloid malignancies. However, unresponsive or resistant to HMA occurs in approximately 50% of patients. ASXL1, one of the most commonly mutated genes across the full spectrum of myeloid malignancies, has been reported to predict a lower overall response rate to HMAs, suggesting an essential need to develop effective therapeutic strategies for the patients with HMA failure. Here, we investigated the impact of ASXL1 on cellular responsiveness to decitabine treatment. ASXL1 deficiency increased resistance to decitabine treatment in AML cell lines and primary mouse bone marrow cells. Transcriptome sequencing revealed significant alterations in genes regulating cell cycle, apoptosis, and histone modification in ASXL1 deficient cells that resistant to decitabine. BIRC5 was identified as a potential target for overcoming decitabine resistance in ASXL1 deficient cells. Furthermore, our experimental evidence demonstrated that the small-molecule inhibitor of BIRC5 (YM-155) synergistically sensitized ASXL1 deficient cells to decitabine treatment. This study sheds light on the molecular mechanisms underlying the ASXL1-associated HMA resistance and proposes a promising therapeutic strategy for improving treatment outcomes in affected individuals.

Robotic living donor hepatectomy is associated with superior outcomes for both the donor and the recipient compared to laparoscopic or open - A single center prospective registry study of 3,448 cases.

Minimally invasive donor hepatectomy is an emerging surgical technique in living donor liver transplantation (LDLT). We examined outcomes across open, laparoscopic, and robotic LDLT using a prospective registry. We analyzed 3,448 cases (1,724 donor-recipient pairs) from Jan 2011 to Mar 2023 (NCT06062706). Among donors, 724 (42%) were female. Adult-to-adult LDLT comprised 1,061 (62%) cases. 646 (37%) of the donors underwent open, 165 (10%) laparoscopic, and 913 (53%) robotic hepatectomies. PRIMARY OUTCOMES: donor overall morbidity was 4% (35/903) for robotic, 8% (13/165) laparoscopic, and 16% (106/646) open (p<0.001). Pediatric and adult recipient mortality was similar among the three donor hepatectomy approaches; robotic 1.5% and 7.0%, compared to 2.3% and 8.3% laparoscopic and 1.6% and 5.5% for open donor surgery, respectively (p=0.802, p=0.564). SECONDARY OUTCOMES: pediatric and adult recipient major morbidity after robotic hepatectomy was 15% and 23%, compared to 25% and 44% laparoscopic and 19% and 31% for open surgery, respectively (p=0.033, p<0.001). Graft and recipient 5-year survival was 90% and 93% for pediatric and 79% and 80% for adults, respectively. In conclusion, robotic LDLT was associated with superior outcomes when compared to the laparoscopic and open approaches. Both donors, and for the first time reported, recipients benefitted with lower morbidity rates in robotic surgery, emphasizing its potential in further advancing this field. IRB APPROVAL ID: RAC 2121012 CLINICALTRIALS.GOV: NCT06062706.

Antiviral activity of Vigna radiata extract against feline coronavirus in vitro.

Feline infectious peritonitis (FIP) is a fatal illness caused by a mutated feline coronavirus (FCoV). This disease is characterized by its complexity, resulting from systemic infection, antibody-dependent enhancement (ADE), and challenges in accessing effective therapeutics. Extract derived from Vigna radiata (L.) R. Wilczek (VRE) exhibits various pharmacological effects, including antiviral activity. This study aimed to investigate the antiviral potential of VRE against FCoV, addressing the urgent need to advance the treatment of FIP. We explored the anti-FCoV activity, antiviral mechanism, and combinational application of VRE by means of in vitro antiviral assays. Our findings reveal that VRE effectively inhibited the cytopathic effect induced by FCoV, reduced viral proliferation, and downregulated spike protein expression. Moreover, VRE blocked FCoV in the early and late infection stages and was effective under in vitro ADE infection. Notably, when combined with VRE, the polymerase inhibitor GS-441524 or protease inhibitor GC376 suppressed FCoV more effectively than monotherapy. In conclusion, this study characterizes the antiviral property of VRE against FCoV in vitro, and VRE possesses therapeutic potential for FCoV treatment.

Systematic investigation of the Borrelia miyamotoi spirochetes in ticks, wildlife and domestic animal hosts in Yunnan province, Southwest China.

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

Performance Comparison of Machine Learning Models for Concrete Compressive Strength Prediction.

This study explores the prediction of concrete compressive strength using machine learning models, aiming to overcome the time-consuming and complex nature of conventional methods. Four models-an artificial neural network (ANN), a multiple linear regression, a support vector machine, and a regression tree-are employed and compared for performance, using evaluation metrics such as mean absolute deviation, root mean square error, coefficient of correlation, and mean absolute percentage error. After preprocessing 1030 samples, the dataset is split into two subsets: 70% for training and 30% for testing. The ANN model, further divided into training, validation (15%), and testing (15%), outperforms others in accuracy and efficiency. This outcome streamlines compressive strength determination in the construction industry, saving time and simplifying the process.

Modular Design of Highly Stable Semiconducting Porous Coordination Polymer for Efficient Electrosynthesis of Ammonia.

Developing highly stable porous coordination polymers (PCPs) with integrated electrical conductivity is crucial for advancing our understanding of electrocatalytic mechanisms and the structure-activity relationship of electrocatalysts. However, achieving this goal remains a formidable challenge because of the electrochemical instability observed in most PCPs. Herein, we develop a "modular design" strategy to construct electrochemically stable semiconducting PCP, namely, Fe-pyNDI, which incorporates a chain-type Fe-pyrazole metal cluster and π-stacking column with effective synergistic effects. The three-dimensional electron diffraction (3D ED) technique resolves the precise structure. Both theoretical and experimental investigation confirms that the π-stacking column in Fe-pyNDI can provide an efficient electron transport path and enhance the structural stability of the material. As a result, Fe-pyNDI can serve as an efficient model electrocatalyst for nitrate reduction reaction (NO3RR) to ammonia with a superior ammonia yield of 339.2 µmol h-1 cm-2 (14677 µg h-1 mgcat. -1) and a faradaic efficiency of 87 % at neutral electrolyte, which is comparable to state-of-the-art electrocatalysts. The in-situ X-ray absorption spectroscopy (XAS) reveals that during the reaction, the structure of Fe-pyNDI can be kept, while part of the Fe3+ in Fe-pyNDI was reduced in situ to Fe2+, which serves as the potential active species for NO3RR.

The status and influencing factors of fatigue in kidney transplant recipients based on the theory of unpleasant symptoms: A cross-sectional study in China.

AIMS: This study describes the incidence of fatigue in kidney transplant recipients and analyses the relationship between physiological factors, psychological factors, situational factors and fatigue in kidney transplant recipients. BACKGROUND: Fatigue, as a common symptom after kidney transplantation, is affected by many factors, but the influence of some factors on the fatigue of kidney transplant recipients is still controversial. DESIGN: This cross-sectional study was designed based on the theory of unpleasant symptoms. METHODS: Our survey involved 307 participants attending the kidney transplant outpatient clinic of a tertiary Class A hospital (Changsha, Hunan, China). Data were collected between February and April 2021 using a structured questionnaire and electronic medical records. Data were analysed using IBM SPSS 25.0 (SPSS Inc.) RESULTS: It was found that the incidence of fatigue in kidney transplant recipients was 53.1%. According to the binary logistic regression analysis, sleep quality, hypokalemia, anxiety, depression and education level were independent risk factors for fatigue in kidney transplant recipients. CONCLUSION: The incidence of fatigue in kidney transplant recipients was high and was influenced by physical, psychological and situational factors. Clinical nurses should assess fatigue levels in a timely and multidimensional manner in clinical practice and provide effective and scientific guidance about fatigue self-coping and symptom management for kidney transplant recipients.

Longitudinal analysis of liver transplant candidates for hepatocellular carcinoma in a single center.

BACKGROUND: Wailitst lost is an critical issue and we investigated the long-term effect of insufficient liver functional reserve at liver transplantation evaluation on waitlist outcomes in patients with hepatocellular carcinoma (HCC). METHODS: Clinical data of patients with HCC waitlisted for liver transplantation were retrospectively collected from a single hospital cohort during the period from 2014 to 2021. Parameters of liver reserve, including cirrhosis, Child-Pugh grade, and Model for End-Stage Liver Disease (MELD) scores, were analyzed for patient survival, after adjustment for tumor factors. RESULTS: Of 292 eligible patients, 94.2% had cirrhosis, 55.8% had Child-Pugh grade B or C, and the median MELD score was 13.2. The median follow-up time was 2.2 years, with a dropout rate of 62.7%. Eighty-nine candidates (30.5%) eventually received liver transplant, including 67 from live donors. The estimated 1-year mortality rate reached 40.6% in 203 patients who remained on the waitlist without receiving a transplant, of whom 143 died. Most deaths were attributed to liver failure (37.1%) and cancer death (35.7%). After we adjusted for tumor confounders, including alpha fetoprotein, primary HCC stage, tumor number at evaluation, and sequential cancer treatment before and while waiting, hazard ratios (HRs) for patient survival were 1.69 (95% confidence interval, 1.18-2.41) for cirrhotic stage B or C, 1.07 (1.04-1.10) for MELD scores, and 1.14 (1.04-1.25) for tumor size at transplant evaluation. Transplantation was a protective disease modifier with adjusted HR 0.22 (0.14-0.33). CONCLUSION: Insufficient liver functional reserve poses more risk than expected to liver transplant waitlist outcomes with HCC.

The role of orphan G protein-coupled receptors in pain.

G protein-coupled receptors (GPCRs), which form the largest family of membrane protein receptors in humans, are highly complex signaling systems with intricate structures and dynamic conformations and locations. Among these receptors, a specific subset is referred to as orphan GPCRs (oGPCRs) and has garnered significant interest in pain research due to their role in both central and peripheral nervous system function. The diversity of GPCR functions is attributed to multiple factors, including allosteric modulators, signaling bias, oligomerization, constitutive signaling, and compartmentalized signaling. This review primarily focuses on the recent advances in oGPCR research on pain mechanisms, discussing the role of specific oGPCRs including GPR34, GPR37, GPR65, GPR83, GPR84, GPR85, GPR132, GPR151, GPR160, GPR171, GPR177, and GPR183. The orphan receptors among these receptors associated with central nervous system diseases are also briefly described. Understanding the functions of these oGPCRs can contribute not only to a deeper understanding of pain mechanisms but also offer a reference for discovering new targets for pain treatment.

Constructing Dynamic Anode/Electrolyte Interfaces Coupled with Regulated Solvation Structures for Long-Term and Highly Reversible Zinc Metal Anodes.

Aqueous zinc ion batteries (AZIBs) show a great potential for next-generation energy storage due to their high safety and high energy density. However, the severe side reactions of zinc negative electrode largely hinder the further application of AZIBs. Herein, trace tris(hydroxymethyl)aminomethane (Tris) additive with rich lone-pair-electrons and zincophilic sites is firstly introduced to achieve long-term and highly reversible Zn plating/stripping. Specifically, Tris not only regulates the solvation structure of Zn2+, but is also adsorbed vertically on the Zn anode surface with a changed coordination intensity during the plating/stripping process of Zn to generate an in situ dynamic adsorption layer for the first time. The dynamic adsorption layer could successively attract the solvated Zn2+ and then promote the de-solvation of the solvated Zn2+ owing to the orientation polarization with regularly-changed applied electric field, the volume rejection effect, and strong intermolecular force towards H2O of the vertically-adsorbed Tris. Therefore, an improved Zn2+-transport kinetics as well as the inhibition of side reactions of Zn anode are successfully realized. Accordingly, the Zn||Zn symmetric cell provides an ultra-long cycle life of 2600 h. Furthermore, the Zn||MnO2 full cell with Tris could demonstrate a high capacity and structural stability for practical applications.

Risk factors analyses associated with postoperative infection in choledochoscopy for intrahepatic bile duct stones (IHDs): a single-center retrospective study in real-world setting.

BACKGROUND: Choledochoscopy is a highly effective approach for managing intrahepatic bile duct stones (IHDs). However, postoperative infection is a common complication that significantly impacts treatment outcomes. Despite its clinical relevance, the risk factors associated with this procedure remain largely unexplored. METHODS: This study focused on a consecutive cohort of patients who underwent choledochoscopy for IHDs at our institution between January 2016 and December 2022. The primary objective was to analyze the relationship between various clinical factors and postoperative infection, and to compare the postoperative infection of different choledochoscopic procedures. RESULTS: The study cohort consisted of 126 patients, with 60 individuals (47.6%) experiencing postoperative infection. Notably, preoperative biliary obstruction (odds ratio [OR] 1.861; 95% confidence interval [CI] 1.314-8.699; p = 0.010) and operation time (OR 4.414; 95% CI 1.635-12.376; p = 0.004) were identified as risk factors for postoperative infection. Additionally, biliary tract infections (60.00%) were primarily responsible for postoperative infection, with Escherichia coli (47.22%) being the predominant bacterial strain identified in bile cultures. Furthermore, biliary tract obstruction (OR 4.563; 95% CI 1.554-13.401; p = 0.006) and body mass index (BMI) (OR 1.186; 95% CI 1.015-1.386; p = 0.031) were determined to be independent risk factors for postoperative biliary tract infection. CONCLUSIONS: The occurrence of postoperative infection in patients undergoing choledochoscopy was primarily associated with the duration of the operation and the presence of preoperative biliary obstruction.

Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.

Ten-year epidemiology and risk factors of cytomegalovirus infection in hematopoietic stem cell transplantation patients in Taiwan.

BACKGROUND: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. METHODS: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. RESULTS: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. CONCLUSION: The study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.

Curcumin analogue NL04 inhibits spinal cord central sensitization in rats with bone cancer pain by inhibiting NLRP3 inflammasome activation and reducing IL-1ß production.

The management and therapy of bone cancer pain (BCP) remain formidable clinical challenges. Curcumin and its analogues have been shown to have anti-inflammatory and analgesic properties. In the present study, we investigated the efficacy of curcumin analogue NL04 (NL04) in modulating inflammation in spinal dorsal horn (SDH), thereby exploring its potential to reduce central sensitization of BCP in a rat model. Differing doses of NL04 and curcumin were administered intrathecally either once (on day 12 of BCP) or over seven consecutive days (from day 6-12 of BCP). Results indicated that the ED50 for NL04 and curcumin ameliorating BCP-induced mechanical hyperalgesia is 49.08 µg/kg and 489.6 µg/kg, respectively. The analgesic effects at various doses of NL04 lasted between 4 and 8 h, with sustained administration over a week maintaining pain relief for 1-4 days, while also ameliorating locomotor gait via gait analysis and reducing depressive and anxiety-like behaviors via open-field and light-dark transition tests. The analgesic effects at various doses of curcumin lasted 4 h, with sustained administration over a week maintaining pain relief for 0-2 days. ELISA, Western blotting, qPCR, and immunofluorescence assays substantiated that intrathecal administration of NL04 on days 6-12 of BCP dose-dependently lowered spinal IL-1ß and IL-18 levels and significantly reduced the expression of IKKß genes and proteins, as well as the downstream cleavage of the trans-Golgi network (TGN). Whole-cell patch-clamp results demonstrated that NL04 inhibits potassium ion efflux in rat primary spinal neurons. Thus, NL04 exhibits significant analgesic effects in a BCP rat model by downregulating IKKß expression and inhibiting neuronal potassium ion efflux, which, in turn, suppresses the activation of NLRP3 inflammasomes and reduces IL-1ß production, potentially ameliorating pain management in BCP.

Risk factors, patterns, and outcome predictors of late recurrence in patients with hepatocellular carcinoma after curative resection: A large cohort study with long-term follow-up results.

BACKGROUND: Late recurrence of hepatocellular carcinoma after curative resection significantly influences long-term patient survival outcomes, and yet it remains understudied. This study aims to explore the risk factors and patterns of late recurrence and predictors of subsequent outcome. METHODS: This single-center retrospective study analyzed 1,701 consecutive patients who achieved a disease-free survival period exceeding 2 years after curative resection for hepatocellular carcinoma between 2001 and 2018. Univariate and multivariate analyses of factors associated with late recurrence and death after recurrence were conducted using Cox's models. RESULTS: The mean age of patients was 60.2 years, with 76.8% being male. During a median follow-up of 8.1 years, 653 patients (38.4%) experienced late recurrence, with median time to recurrence being 4.0 years (interquartile range, 2.7-6.0). Factors such as age >60, chronic hepatitis C, cirrhosis, high albumin-bilirubin grade, absence of family history, multiple tumors, satellite nodules, alpha-fetoprotein levels <400 ng/mL, and minor hepatic resection were identified as risk factors for late recurrence. Among patients with late recurrence, 131 (20.1%) underwent surgical treatment, 272 (41.7%) received radiofrequency ablation, and 27 (4.1%) exhibited extrahepatic lesions. A higher-high albumin-bilirubin grade, recurrent tumor >3 cm, and nonsurgical treatment emerged as predictors of death after late recurrence. CONCLUSION: Over one-third of patients who remain disease-free for more than 2 years postresection will experience late recurrence during subsequent follow-up. For 2-year disease-free survivors, risk factors for late recurrence differ from early recurrence. Treating underlying hepatitis is of paramount importance, given its association with both the risk of late recurrence and survival outcomes post-recurrence.

Regulating TKT activity inhibits proliferation of human acute lymphoblastic leukemia cells.

Among pediatric blood cancers, acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy. Within ALL, T-cell acute lymphoblastic leukemia (T-ALL) accounts for 10 to 15% of all pediatric cases, and ~25% of adult cases. For T-ALL, its recurrence and relapse after treatment remain problematic. Therefore, it is necessary to develop new therapies for T-ALL. Recent studies suggested regulating energy metabolism is a novel approach to inhibit tumor growth, likely a promising treatment. Transketolase (TKT) is an important enzyme for modulating glucose metabolize in the pentose phosphate pathway (PPP). In this study, we treated T-ALL cells with different doses of niclosamide and primary T-ALL PBMCs were analyzed by RNA sequencing. T-ALL cells treated with niclosamide were analyzed with the Western blotting and TKT activity assay. Metabolism of T-ALL cells was evaluated by ATP assay and seahorse analyses. Lastly, we used a T-ALL xenograft murine model to determine effects of TKT knockdown on T-ALL tumor growth. Tumor samples were analyzed by H&E and IHC stainings. We found that niclosamide reduced T-ALL cell viability, and reduced expressions of TKT, Transketolase-Like Protein 1/2 (TKTL1/2) and transaldolase. In addition, niclosamide inhibited TKT enzyme activity, aerobic metabolism and glycolysis, finally leading to lower production of ATP. TKT knockdown inhibited tumor growth of xenograft T-ALL mice. Findings showed that niclosamide inhibits T-ALL cell growth by inhibiting TKT and energy metabolism.

Humoral Cytokine Levels in Patients with Herpes Zoster: A Meta-Analysis.

Background: The neurocutaneous disease caused by the reactivation of varicella-zoster virus (VZV) is called herpes zoster (HZ). The virus remains in the spinal cord back root after the chickenpox disappears. Diminished immune function can reactivate VZV, causing severe neuropathic pain that can last for months or even years, leading to postherpetic neuralgia (PHN), which severely affects the patient's quality of life. Much literature compares various cytokine levels in the body fluids HZ and PHN patients; however, no studies comprehensively evaluate them. Methods: The Cochrane Library, PubMed, Web of Science, and Medline were screened for studies on cytokine levels in body fluids of HZ and PHN patients in the English language. Healthy individuals were selected as the control group, and the standardized mean difference (SMD) between the case and control groups was imputed using a fixed-effects or random-effects model and expressed as a 95% confidence interval (CI). The Newcastle-Ottawa Scale (NOS) was used to assess article quality. Results: This meta-analysis included 13 articles with 1373 participants. Compared with the control group, the HZ group had significantly higher levels of interleukin (IL)-4, IL-6, IL-10, Hcy, and C-reactive protein (CRP), whereas the levels of CD3+ T and CD4+ T lymphocytes were reduced. Additionally, PHN patients had significantly higher levels of IL-6 and IL-1ß compared with the control group. Conclusion: This meta-analysis provides compelling evidence that CRP, Hcy, IL-1ß, IL-4, IL-6, IL-8, and IL-10 are associated with the genesis and development of HZ and PHN. These markers can be used to improve the diagnosis and treatment of these diseases.Furthermore, for making the results more convincing, it is necessary to harmonize sample acquisition techniques and analytical methods and also require larger, more rigorously designed studies with broader subgroups and sex/age-matched controls.

Clinical manifestations and risk factors for COVID-19 and its severity in patients with hematological malignancies.

BACKGROUND: Patients with hematological malignancies (HM) were at a high risk of developing severe disease from coronavirus disease 2019 (COVID-19). We aimed to assess the clinical outcome of COVID-19 in hospitalized patients with HM. METHODS: Adult patients with HM who were hospitalized with a laboratory-confirmed COVID-19 between May, 2021 and November, 2022 were retrospectively identified. Primary outcome was respiratory failure requiring mechanical ventilation or mortality within 60 days after hospitalization. We also analyzed associated factors for de-isolation (defined as defervescence with a consecutive serial cycle threshold value > 30) within 28 days. RESULTS: Of 152 eligible patients, 22 (14.5%) developed respiratory failure or mortality in 60 days. Factors associated with developing respiratory failure that required mechanical ventilation or mortality included receipt of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) (adjusted hazards ratio [aHR], 5.10; 95% confidence interval [CI], 1.64-15.85), type 2 diabetes mellitus (aHR, 2.47; 95% CI, 1.04-5.90), lymphopenia at admission (aHR, 6.85; 95% CI, 2.45-19.15), and receiving <2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines (aHR, 3.00; 95% CI, 1.19-7.60). Ninety-nine (65.1%) patients were de-isolated in 28 days, against which two hazardous factors were identified: receipt of B-cell depletion therapies within one year prior to COVID-19 (aHR, 0.55, 95% CI, 0.35-0.87) and lymphopenia upon admission (aHR, 0.65; 95% CI, 0.43-1.00). CONCLUSION: We found a high rate of respiratory failure and mortality among patients with HM who contracted the SARS-CoV-2. Factors associated with developing respiratory failure or mortality in 60 days included receipt of allo-HSCT, type 2 diabetes mellitus and lymphopenia upon admission. Having received ≥2 doses of vaccination conferred protection against clinical progression.

Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population.

BACKGROUND: It is uncertain whether rare NOTCH3 variants are associated with stroke and dementia in the general population and whether they lead to alterations in cognitive function. This study aims to determine the associations of rare NOTCH3 variants with prevalent and incident stroke and dementia, as well as cognitive function changes. METHODS AND RESULTS: In the prospective community-based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow-up analysis, 1007 participants were included in the stroke analysis, and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare NOTCH3 variants were defined as variants with minor allele frequency <1%. A total of 137 rare NOTCH3 carriers were enrolled in the baseline study. At baseline, rare NOTCH3 variant carriers had higher rates of stroke (8.8% versus 5.6%) and dementia (2.9% versus 0.8%) compared with noncarriers. After adjustment for associated risk factors, the epidermal growth factor-like repeats (EGFr)-involving rare NOTCH3 variants were associated with a higher risk of prevalent stroke (odds ratio [OR], 2.697 [95% CI, 1.266-5.745]; P=0.040) and dementia (OR, 8.498 [95% CI, 1.727-41.812]; P=0.032). After 5 years of follow-up, we did not find that the rare NOTCH3 variants increased the risk of incident stroke and dementia. There was no statistical difference in the change in longitudinal cognitive scale scores. CONCLUSIONS: Rare NOTCH3 EGFr-involving variants are genetic risk factors for stroke and dementia in the general Chinese population.