China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

[Epidemioloical characteristics and economic burden analysis of palmoplantar pustulosis in urban areas of China].

Objective: To analyze the epidemiological characteristics and economic burden of palmoplantar pustulosis (PPP) in China. Methods: A population-based retrospective study was conducted using the data from China's Urban Basic Medical Insurance data from January 1, 2012, to December 31, 2016. International Classification of Diseases code and diagnoses in Chinese for PPP were used to identify cases and estimate the prevalence, incidence, and cost. Subgroup analyses were performed according to age and sex, and sensitivity analyses were conducted to evaluate the robustness of the results. Age-adjusted prevalence rates were calculated based on the 2010 national census data. Results: The crude prevalence and incidence rate of PPP in 2016 were 2.730/100 000 (95%CI: 2.218/100 000-3.242/100 000) and 1.556/100 000 (95%CI: 1.154/100 000-1.958/100 000), and the prevalence rate of females (2.910/100 000) was higher than that of males (2.490/100 000, χ2=97.48, P=0.001). The incidence rate of females (1.745/100 000) was also higher than that of males (1.418/100 000, χ2=85.02, P=0.001). The age peak of incidence and prevalence of patients with PPP was in the 30-39-year age group and a small peak existed in the 0-3-year age group among people under 20 years old. From 2012 to 2016, the average number of visits was (2.44±0.04) per patient, and the total per-capita cost per year was (982.40±39.19) yuan. Conclusion: In 2016, the prevalence and incidence rate of PPP in China were higher in females than in males, and the highest age peak was in the 30-39-year age group.

[Efficacy and safety of roxadustat in the treatment of refractory non-severe aplastic anemia].

Objective: To evaluate the efficacy and safety of roxadustat in patients with refractory non-severe aplastic anemia (NSAA) . Methods: The clinical data of patients with refractory NSAA who had been treated with roxadustat continuously for at least 3 months and followed up for more than 6 months at Peking Union Medical College Hospital from October 2020 to August 2022 were retrospectively collected. The demographic information, clinical data, treatment efficacy, adverse reactions, and outcomes were evaluated, and the factors influencing efficacy were analyzed. Results: A total of 41 patients were included. The male-to-female ratio was 16∶25, and the median age was 52 (18-84) years. The median duration of roxadustat treatment was 5 (3-20) months, and the median follow-up was 15 (6-26) months. Hematologic improvement-erythroid (HI-E) was 12.2%, 29.3%, 46.3%, 43.9%, and 30.3% at 1, 2, 3, 6, and 12 months, respectively. The rate of transfusion independence was 28.5%, 38.1%, and 33.3% at 3, 6, and 12 months, respectively. Hemoglobin returned to normal in some patients after treatment with roxadustat. The incidence of adverse events was 22%, all of which were grade Ⅰ-Ⅱ and recoverable. No factors that could affect HI-E were identified. By the end of follow-up, 45% of the patients relapsed, with a median time to relapse of 7 (3-12) months. No clonal evolution was observed, and one patient died. Conclusion: Roxadustat effectively improved anemia with good tolerance in patients with refractory NSAA.

Clinical study of tirofiban compared to low molecular weight heparin in the antithrombotic treatment of progressive pontine infarction.

OBJECTIVE: To investigate the efficacy and safety of tirofiban and low molecular weight heparin (LMWH) in the treatment of patients undergoing acute progressive pontine infarction. PATIENTS AND METHODS: Patients with acute progressive pontine infarction who were hospitalized in the Neurology Department from June 2021 to June 2023 were included in the study and randomly divided into two groups, namely the experimental group (tirofiban group) and the control group (LMWH group). All patients in both groups were required to receive conventional comprehensive treatment and dual antiplatelet therapy with aspirin + clopidogrel at the beginning of admission. The National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) were used to evaluate the neurological deficits on the first day of admission, the next day with stroke progression, and at discharge after treatment with tirofiban and LMWH, respectively in the two groups. The modified Rankin Scale was employed to assess prognosis on the 90th day after treatment. Clinical adverse events were followed up for 90 days, comparing the clinical efficacy and safety of the two treatment methods. RESULTS: There was no statistical significance in NIHSS score and Barthel Index between the tirofiban group and the LMWH group on the first day of admission and the next day with stroke progression (p > 0.05). After stroke progression, tirofiban and LMWH were separately used for treatment in the two groups. We found that the NIHSS score of the tirofiban group was lower than that of the LMWH group, and the Barthel Index score was higher than that of the LMWH group at discharge (p < 0.05). After three months of follow-up, the mRS score of the tirofiban group was dramatically higher than that of the LMWH group (p < 0.05). No significant harmful or adverse reactions, such as bleeding events, were found in the two groups (p > 0.05). CONCLUSIONS: Tirofiban may be more effective and safer than LMWH in controlling the progression of acute pontine infarction, but further and large-sample studies are still needed to confirm this finding.

Comparison of laparoscopic and open inguinal-hernia repair in elderly patients: the experience of two comprehensive medical centers over 10 years.

PURPOSE: The safety of laparoscopic inguinal-hernia repair must be carefully evaluated in elderly patients. Very little is known regarding the safety of the laparoscopic approach in elderly patients under surgical and medical co-management (SMC). Therefore, this study evaluated the safety of the laparoscopic approach in elderly patients, especially patients with multiple comorbidities under SMC. METHODS: From January 2012 to December 2021, patients aged ≥ 65 years who underwent open or laparoscopic inguinal-hernia repair during hospitalization were consecutively enrolled. Postoperative outcomes included major and minor operation-related complications, and other adverse events. To reduce potential selection bias, propensity score matching was performed between open and laparoscopic groups based on patients' demographics and comorbidities. RESULTS: A total of 447 elderly patients who underwent inguinal-hernia repair were enrolled, with 408 (91.3%) underwent open and 39 (8.7%) laparoscopic surgery. All postoperative outcomes were comparable between open and laparoscopic groups after 1:1 propensity score matching (all p > 0.05). Moreover, compared to the traditional care group (n = 360), a higher proportion of the SMC group (n = 87) was treated via the laparoscopic approach (18.4% vs. 6.4%, p = 0.00). In the laparoscopic approach subgroup (n = 39), patients in the SMC group (n = 16) were older with multiple comorbidities but were at higher risks of only minor operation-related complications, compared to those in the traditional care group. CONCLUSIONS: Laparoscopic inguinal-hernia repair surgery is safe for elderly patients, especially those with multiple comorbidities under SMC.

[The effect of glucose-6-phosphate dehydrogenase deficiency on allogeneic hematopoietic stem cell transplantation in patients with hematological disorders].

Objectives: To determine the effect of glucose-6-phosphate-dehydrogenase (G6PD) deficiency on patients' complications and prognosis following allogeneic stem cell hematopoietic transplantation (allo-HSCT) . Methods: 7 patients with G6PD deficiency (study group) who underwent allo-HSCT at Peking University People's Hospital from March 2015 to January 2021 were selected as the study group, and thirty-five patients who underwent allo-HSCT during the same period but did not have G6PD deficiency were randomly selected as the control group in a 1∶5 ratio. Gender, age, underlying diseases, and donors were balanced between the two groups. Collect clinical data from two patient groups and perform a retrospective nested case-control study. Results: The study group consisted of six male patients and one female patient, with a median age of 37 (range, 2-45) years old. The underlying hematologic diseases included acute myeloid leukemia (n=3), acute lymphocytic leukemia (n=2), and severe aplastic anemia (n=2). All 7 G6PD deficiency patients achieved engraftment of neutrophils within 28 days of allo-HSCT, while the engraftment rate of neutrophils was 94.5% in the control group. The median days of platelet engraftment were 21 (6-64) d and 14 (7-70) d (P=0.113). The incidence rates of secondary poor graft function in the study group and control group were 42.9% (3/7) and 8.6% (3/35), respectively (P=0.036). The CMV infection rates were 71.4% (5/7) and 31.4% (11/35), respectively (P=0.049). The incidence rates of hemorrhagic cystitis were 57.1% (4/7) and 8.6% (3/35), respectively (P=0.005), while the bacterial infection rates were 100% (7/7) and 77.1% (27/35), respectively (P=0.070). The infection rates of EBV were 14.3% (1/7) and 14.3% (5/35), respectively (P=1.000), while the incidence of fungal infection was 14.3% (1/7) and 25.7% (9/35), respectively (P=0.497). The rates of post-transplant lymphoproliferative disease (PTLD) were 0% and 5.7%, respectively (P=0.387) . Conclusions: The findings of this study indicate that blood disease patients with G6PD deficiency can tolerate conventional allo-HSCT pretreatment regimens, and granulocytes and platelets can be implanted successfully. However, after transplantation, patients should exercise caution to avoid viral infection, complications of hemorrhagic cystitis, and secondary poor graft function.

Head-to-head comparison of prostate-specific membrane antigen positron emission tomography/computed tomography and multiparametric magnetic resonance imaging in the detection of biochemical recurrence of prostate cancer: a systematic review and meta-analysis.

AIM: Our main goal of this meta-analytical analysis was to evaluate the diagnostic effectiveness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) against multiparametric magnetic resonance imaging (mpMRI) in the context of identifying biochemical recurrence in patients with prostate cancer (PCa). MATERIALS AND METHODS: A thorough search covering articles published until March 2023 was carried out across major databases such as PubMed, Embase, and Web of Science. Studies examining the direct comparison of PSMA PET/CT and mpMRI in patients with PCa suffering biochemical recurrence were included in the inclusion criteria. Using the renowned Quality Assessment of Diagnostic Performance Studies-2 technique, each study's methodological rigor was assessed. RESULTS: We analyzed data from six eligible studies involving 290 patients in total. The combined data showed that for PSMA PET/CT and mpMRI, respectively, the pooled overall detection rates for recurrent PCa after definitive treatment were 0.69 (95% confidence interval [CI]: 0.45-0.89) and 0.70 (95% CI: 0.44-0.91). The detection rates for local recurrence were specifically 0.52 (95% CI: 0.39-0.65) and 0.62 (95% CI: 0.31-0.89), while they were 0.50 (95% CI: 0.26-0.74) and 0.32 (95% CI: 0.18-0.48) for lymph node metastasis. Notably, there was no discernible difference between the two imaging modalities in terms of the overall detection rate (P = 0.95). The detection rates for local recurrence and lymph node metastasis did not differ statistically significantly (P = 0.55, 0.23). CONCLUSION: The performance of PSMA PET/CT and mpMRI in identifying biochemical recurrence in PCa appears to be comparable. However, the meta-analysis' findings came from research with modest sample sizes. In this context, more extensive research should be conducted in the future.

[Role of innate lymphoid cells in oral squamous cell carcinoma microenvironment].

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. It has a high incidence, strong invasion ability, easy metastasis, poor curative effect, and poor prognosis. Innate lymphoid cells (ILCs) are an important part of immune cells located in the mucosal barrier, which play an important role in the occurrence, development and outcome of tumors. ILCs are the key cells for decoding the regulatory mechanism of tumor microenvironment and the signatures for tumor progression. This paper reviewed the latest progress on ILCs, summarized the possible characteristics and functions of ILCs in the microenvironment of OSCC, and explored the relationship between ILCs and the occurrence, development and immunotherapy of OSCC.

[Multiple pulmonary nodules with cavity formation].

A 64-year-old female patient was admitted to Beijing Chao-Yang Hospital on February 21, 2023 because of right-sided chest pain for more than 4 years and left-sided chest pain for more than 9 months. She had a past medical history of previous tuberculosis and rheumatoid arthritis. A chest CT in October 2018 revealed multiple pulmonary nodules. A CT-guided biopsy showed no tumors, and adenosine deaminase levels in the pleural effusion were elevated, suggesting a high likelihood of tuberculosis. As a result, anti-tuberculosis treatment was initiated in March 2019. In December 2019, she underwent a right lower lobe resection due to localized hydropneumothorax on the right side. Postoperative pathology unveiled granulomatous inflammation with necrosis. A chest CT in May 2020 showed a significant increase in nodules and cavities. In January 2023, a diagnosis of cryptococcal pneumonia was considered, and she was prescribed oral fluconazole. Finally, the diagnosis of pulmonary rheumatoid nodules was confirmed after a pathological consultation of the postoperative specimen. After one month of treatment with oral prednisone and mycophenolate mofetil, a follow-up chest CT showed improvement. It was recommended that she continue with her current treatment and undergo regular chest CT scans.

[Effect of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients underwent haploidentical stem cell transplantation].

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

[Clinical features and risk factors for invasive fungal sinusitis after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT. Methods: Nineteen patients with IFR after allo-HSCT at Peking University People's Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) . Results: Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10-59) years. The median IFR onset time was 68 (9-880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation (P=0.021) , hemorrhagic cystitis after transplantation (P=0.012) , delayed platelet engraftment (P=0.008) , and lower transplant mononuclear cell count (P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively (P<0.01) . Conclusion: Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.

Clinical and cardiac MRI characteristics: prognosis in patients with alcoholic cardiomyopathy.

AIMS: Alcoholic cardiomyopathy (ACM) is recognized as a type of non-ischemic dilated cardiomyopathy (DCM). To date, the clinical prognosis of ACM remains a topic of debate in previous studies and there are limited studies on its cardiac MRI characteristics. The aim of this study was to summarize the clinical and MRI features of ACM patients and to identify the predictors of adverse prognosis based on clinical characteristics and MRI imaging findings. MATERIALS AND METHODS: Adult patients who were clinically diagnosed with ACM and underwent enhanced CMR between September 2015 and August 2022 were retrospectively enrolled. The primary endpoints were major adverse cardiovascular events, including cardiac-related death, heart transplantation, hospitalization for heart failure and life-threatening ventricular arrhythmias (sustained ventricular tachycardia, ventricular fibrillation, or ICD shock). The risk factors associated with these primary end points were identified using multivariable Cox analysis. RESULTS: A total of 62 ACM patients (50 ± 9 years, 62 men) were included. The majority of patients presented with symptoms of heart failure. Over a median follow-up period of 30.3 months (IQR 12.2-57.7 months), 24 patients reached the primary endpoints. For clinical variables, multivariable analysis showed that drinking duration (HR=1.05; 95%CI:1.01, 1.11; p=0.03) and persistent drinking (HR=3.71; 95%CI:1.46, 9.44; p=0.01) were associated with MACE. For CMR variables, late gadolinium enhancement (LGE) percent (HR = 1.09; 95% CI: 1.03, 1.14; p<0.001) stood out as an independent predictor for MACE. CONCLUSIONS: In ACM patients, persistent drinking and cardiac MRI-defined myocardial scar were associated with adverse outcomes such as cardiac death, heart transplantation, hospitalization for heart failure or life-threatening ventricular arrhythmias.

The combination treatment of oncolytic adenovirus H101 with nivolumab for refractory advanced hepatocellular carcinoma: an open-label, single-arm, pilot study.

BACKGROUND: H101, an innovative oncolytic adenovirus, has shown potential in modifying the tumor microenvironment from immunologically 'cold' to 'hot'. When combined with nivolumab, a programmed cell death protein 1 inhibitor, this synergy may offer substantial therapeutic benefits beyond the capabilities of each agent alone. PATIENTS AND METHODS: In this pilot study, we assessed the efficacy and safety of combining H101 with nivolumab in advanced hepatocellular carcinoma (HCC) patients who failed prior systemic therapy. The participants received initial oncolytic virus (OV) pretreatment with intratumoral H101 injections (5.0 × 1011 vp/0.5 ml/vial, two vials per lesion) on days 1 and 3. Combination therapy started on day 8, with H101 administered every 2 or 4 weeks and nivolumab (240 mg) injections every 2 weeks. Treatment continued up to 12 months or until disease progression, intolerable toxicity, consent withdrawal, or study conclusion. The primary endpoint was the objective response rate (ORR). RESULTS: Between March 2020 and March 2022, 18 of 21 screened patients were assessable, showing an ORR of 11.1% [two cases of partial response (PR) and five cases of stable disease], with extrahepatic injections often leading to favorable outcomes. The disease control rate stood at 38.9%, with a 6-month survival rate of 88.9%. Median progression-free survival was 2.69 months, and overall survival (OS) was 15.04 months. Common adverse events included low-grade fever (100%) and pain related to centesis (33.3%), and no grade 3/4 events were reported. Significantly, local H101 injection showed potential in reversing immune checkpoint inhibitor resistance, evidenced by over 2.5 years of extended OS in PR cases with low α-fetoprotein. Additionally, decreasing neutrophil-to-lymphocyte ratio during OV pretreatment may predict positive outcomes. CONCLUSIONS: This study demonstrates the potential efficacy of combining H101 with nivolumab in treating refractory advanced HCC, with well-tolerated toxicities.

Development of terpenoid repellents against Aedes albopictus: a combined study of biological activity evaluation and computational modelling.

To explore novel terpenoid repellents, 22 candidate terpenoid derivatives were synthesized and tested for their electroantennogram (EAG) responses and repellent activities against Aedes albopictus. The results from the EAG experiments revealed that 5-(2-hydroxypropan-2-yl)-2-methylcyclohex-2-en-1-yl formate (compound 1) induced distinct EAG responses in female Aedes albopictus. At concentrations of 0.1, 1, 10, 100, and 1000 mg/L, the EAG response values for compound 1 were 179.59, 183.99, 190.38, 193.80, and 196.66 mV, demonstrating comparable or superior effectiveness to DEET. Repellent activity analysis indicated significant repellent activity for compound 1, closest to the positive control DEET. The in silico assessment of the ADMET profile of compound 1 indicates that it successfully passed the ADMET evaluation. Molecular docking studies exhibited favourable binding of compound 1 to the active site of the odorant binding protein (OBP) of Aedes albopictus, involving hydrophobic forces and hydrogen bond interactions with residues in the OBP pocket. The QSAR model highlighted the influential role of hydrogen-bonding receptors, positively charged surface area of weighted atoms, polarity parameters of molecules, and maximum nuclear-nuclear repulsion force of carbon-carbon bonds on the relative EAG response values of the tested compounds. This study holds substantial significance for the advancement of new terpenoid repellents.

[Research progress of direct-acting antiviral drugs in the treatment of chronic hepatitis C-related cirrhosis].

Chronic hepatitis C is a kind of viral hepatitis caused by hepatitis C virus infection, which can further progress to cirrhosis, liver failure, hepatocellular carcinoma, and even death. Presently, there is no preventive vaccine yet. Therefore, preventing infection and safe and effective drug treatment are currently the most effective strategies for dealing with hepatitis C virus infection. Since 2014, the clinical application of direct-acting antiviral drugs has brought revolutionary changes to the treatment of chronic hepatitis C. Direct-acting antiviral drugs have an excellent hepatitis C virus clearance effect, are well tolerated, have a good safety profile, and can significantly improve liver function, metabolic disorders, immune dysfunction, etc. However, some studies have pointed out that even if the hepatitis C virus is cleared during the treatment of chronic hepatitis C-related cirrhosis with direct-acting antiviral drugs, a considerable proportion of patients still have severe liver failure, hepatocellular carcinoma, and even liver disease-related death, so there are still some problems in the treatment of chronic hepatitis C- related cirrhosis with direct-acting antiviral drugs that need to be further explored. This article reviews the research progress of direct-acting antiviral drugs so as to provide meaningful references for the treatment of patients with chronic hepatitis C-related cirrhosis.

Return on investment of fracture liaison services: a systematic review and analysis.

Fracture liaison services (FLS) have been proven clinically effective and cost-effective in preventing subsequent fractures among patients with an existing fragility fracture. Little is known about their monetary benefits such as their return on investment (ROI). This systematic review aimed to investigate the ROI of FLS and identify the FLS characteristics with better ROI. Studies on the cost-effectiveness of FLS published between January 2000 and December 2022 were searched from MEDLINE, EMBASE, PubMed, and Cochrane Central. Two independent reviewers conducted study selection and data extraction. ROI was calculated based on the difference between monetary benefits and FLS costs divided by the FLS costs. Subgroup analysis of ROI was performed across FLS types and FLS design details. A total of 23 FLS were included in this review. The majority of them were targeting patients aged over 50 years having fractures without identified sites. The mean ROI of these FLS was 10.49 (with a median ROI of 7.57), and 86.96% of FLS had positive ROI. FLS making treatment recommendations yielded the highest ROI (with a mean ROI of 18.39 and a median of 13.60). Incorporating primary care providers (with a mean ROI of 16.04 and a median of 13.20) or having them as program leaders (with a mean ROI of 12.07 and a median of 12.07) has demonstrated a high ROI. FLS for specific fracture sites had great monetary return. Intensive FLS such as type A and B FLS programs had higher ROI than non-intensive type C and D FLS. This review revealed a 10.49-fold monetary return of FLS. Identified characteristics contributing to greater economic return informed value-for-money FLS designs. Findings highlight the importance of FLS and the feasibility of expanding their contribution in mitigating the economic burden of osteoporotic fracture and are conducive to the promotion of FLS internationally.

[Association of urinary cadmium level with body mass index and body circumferences among older adults over 65 years old in 9 longevity areas of China].

Objective: To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China. Methods: Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 µg/g·creatinine, middle:0.77-1.69 µg/g·creatinine, high:≥1.69 µg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model. Results: The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) µg/g·creatinine, and the BMI was (22.70±3.82) kg/m2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 µg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI (Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference (Plinear<0.001), hip circumference (Plinear<0.001), and calf circumference (Plinear<0.001). Conclusion: Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

[Evaluation of anticoagulant effect and predicted dose of low molecular weight heparin in hemodialysis by anti-â ©a factor activity].

The purpose of this study was to explore the reasonable dose of low molecular weight heparin (LMWH) in hemodialysis (HD) and the strategy of preventing extracorporeal circuit coagulation (ECC). A retrospective case-control study included patients who used LMWH for anticoagulation during maintenance hemodialysis (MHD) in the Hemodialysis Center of Beijing Hospital from December 2020 to January 2021. Basic data such as weight, height, basic kidney disease, dialysis age and anti-Ⅹa factor activity before, during and after dialysis were collected. A total of 46 patients were enrolled in this study, including 5 patients in coagulation group (10.9%) and 41 patients in non-coagulation group (89.1%). The anti-Ⅹa factor activity reached its peak at 0.5 h after the start of HD. The level of anti-Ⅹa factor was incorporated into the receiver operating characteristic curve (ROC curve). The results showed that the area under the ROC curve (AUC) was 0.802 (95% confidence interval: 0.651-0.54, P=0.029), and the cutoff was 0.31 IU/ml (sensitivity 1, specificity 0.683). It is suggested that the body surface area should be used as the basis to estimate the anticoagulant dose of LMWH in HD, and the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml, which is of diagnostic value for ECC. In addition, the results of binary logistic regression analysis showed that dialysis age was an independent risk factor for ECC (OR value 1.319, 95%CI 1.052-1.654, P=0.017). In summary, this study reveals that dialysis age may be a risk factor for ECC and that the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml can be used as a potential diagnostic cut-off point for ECC in HD patients, which provides a scientific basis for monitoring strategies to prevent blood coagulation in HD filters.