Objective·To investigate the effect of plasma exchange combined with classical chemotherapy on renal function in patients with multiple myeloma(MM).Methods·A retrospective analysis was conducted on data from patients newly diagnosed with MM in the Department of Hematology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,between October 2021 and September 2023.Sixty-eight MM patients admitted from October 2021 to September 2022 served as the control group,and 41 patients admitted from October 2022 to September 2023 comprised the experimental group.The control group received classical chemotherapy for MM[PAD(bortezomib+adriamycin+dexamethasone)or PCD(bortezomib+cyclophosphamide+dexamethasone)],and the experimental group underwent plasma exchange before classic chemotherapy.The frequency of plasma exchange was determined according to the clearance rate of M-protein in patients,with the criterion being a reduction of more than 40%in plasma M-protein levels after exchange,and the total number of exchanges ranged from 1 to 3 sessions.After 2 chemotherapy courses,the free light chain difference(dFLC),serum creatinine(Scr),and other renal function indexes were compared between the two groups.Results·Compared with the control group,the experimental group showed no statistically significant difference in dFLC levels.The Scr level decreased[67.00(54.00,75.00)μmol/L vs 77.50(63.00,94.00)μmol/L,P=0.011],and the estimated glomerular filtration rate(eGFR)increased[97.80(92.80,101.30)mL/(min·1.73 m2)vs 85.80(61.35,95.35)mL/(min·1.73 m2),P<0.001]after treatment.Before treatment,the numbers of patients with MM-related severe renal injury[eGFR<50 mL/(min·1.73 m2)]were 41 in the control group and 28 in the experimental group.After treatment,8 patients(19.51%)in the control group achieved complete renal response[eGFR≥60 mL/(min·1.73 m2)],while 12 patients(42.86%)in the experimental group achieved the same,with the difference being statistically significant(P=0.036).After two courses of treatment,the overall response rates(ORR)of the control group and the experimental group were 76.47%and 92.68%,respectively,and the difference in overall therapeutic efficacy was statistically significant(P=0.031).Conclusion·Plasma exchange combined with classical chemotherapy can significantly reduce the Scr levels and increase eGFR in MM patients within a short period,ameliorating the MM-related renal impairment to some extent and improving clinical treatment outcomes.

Objective·To investigate the effect of plasma exchange combined with classical chemotherapy on renal function in patients with multiple myeloma(MM).Methods·A retrospective analysis was conducted on data from patients newly diagnosed with MM in the Department of Hematology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,between October 2021 and September 2023.Sixty-eight MM patients admitted from October 2021 to September 2022 served as the control group,and 41 patients admitted from October 2022 to September 2023 comprised the experimental group.The control group received classical chemotherapy for MM[PAD(bortezomib+adriamycin+dexamethasone)or PCD(bortezomib+cyclophosphamide+dexamethasone)],and the experimental group underwent plasma exchange before classic chemotherapy.The frequency of plasma exchange was determined according to the clearance rate of M-protein in patients,with the criterion being a reduction of more than 40%in plasma M-protein levels after exchange,and the total number of exchanges ranged from 1 to 3 sessions.After 2 chemotherapy courses,the free light chain difference(dFLC),serum creatinine(Scr),and other renal function indexes were compared between the two groups.Results·Compared with the control group,the experimental group showed no statistically significant difference in dFLC levels.The Scr level decreased[67.00(54.00,75.00)μmol/L vs 77.50(63.00,94.00)μmol/L,P=0.011],and the estimated glomerular filtration rate(eGFR)increased[97.80(92.80,101.30)mL/(min·1.73 m2)vs 85.80(61.35,95.35)mL/(min·1.73 m2),P<0.001]after treatment.Before treatment,the numbers of patients with MM-related severe renal injury[eGFR<50 mL/(min·1.73 m2)]were 41 in the control group and 28 in the experimental group.After treatment,8 patients(19.51%)in the control group achieved complete renal response[eGFR≥60 mL/(min·1.73 m2)],while 12 patients(42.86%)in the experimental group achieved the same,with the difference being statistically significant(P=0.036).After two courses of treatment,the overall response rates(ORR)of the control group and the experimental group were 76.47%and 92.68%,respectively,and the difference in overall therapeutic efficacy was statistically significant(P=0.031).Conclusion·Plasma exchange combined with classical chemotherapy can significantly reduce the Scr levels and increase eGFR in MM patients within a short period,ameliorating the MM-related renal impairment to some extent and improving clinical treatment outcomes.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective:To explore the influence of non-motor symptoms on the change trajectory of early activities of daily living in patients with Parkinson disease, and to provide a reference for medical staff to implement intervention measures for people with low levels of activities of daily living in the preclinical stage.Methods:The longitudinal follow-up data of 431 patients with Parkinson disease in the Parkinson's progression Markers Initiative from baseline to five consecutive years after enrollment were selected by convenience sampling method in July 2024, including the scores of aceivities of daily living, the Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire, etc. A latent class growth model classified change trajectory of activities of daily living, and the influencing factors were analyzed by univariate and binary Logistic regression.Results:Among the 431 patients, 260 were male and 171 were female, with an average age of (61.30 ± 9.60) years. The scores of activities of daily living of the patients at baseline, 12 months after enrollment, 36 months after enrollment, and 60 months after enrollment were (5.97 ± 4.30), (7.20 ± 4.61), (8.90 ± 5.60), and (10.57 ± 6.93) points, respectively. The model identified two types of trajectories: rapid decline in low activities of daily living group (25.3%, 109/431) and slow decline in lower activities of daily living group (74.7%, 322/431). The binary Logistic regression results showed that apathy ( OR=0.374, 95% CI 0.189-0.739), fatigue ( OR=0.261, 95% CI 0.138-0.495), University of Pennsylvania Smell Identification Test ( OR=1.039, 95% CI 1.005-1.074), the Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire ( OR=0.880, 95% CI 0.795-0.973), and the gastrointestinal score of the Scales for Outcomes in PD-Autonomic ( OR=0.724, 95% CI 0.630-0.832) were independent influencing factors for the classification of the change trajectory of activities of daily living in patients with Parkinson disease (all P<0.05). Conclusions:Patients with Parkinson disease exhibit a decreasing trend in early activities of daily living, emphasizing the need for targeted interventions in those with fatigue, apathy, and high Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire and Scales for Outcomes in Parkinson disease-Autonomic gastrointestinal scores to possibly decelerate disease advancement.

Objective:To explore the influence of non-motor symptoms on the change trajectory of early activities of daily living in patients with Parkinson disease, and to provide a reference for medical staff to implement intervention measures for people with low levels of activities of daily living in the preclinical stage.Methods:The longitudinal follow-up data of 431 patients with Parkinson disease in the Parkinson's progression Markers Initiative from baseline to five consecutive years after enrollment were selected by convenience sampling method in July 2024, including the scores of aceivities of daily living, the Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire, etc. A latent class growth model classified change trajectory of activities of daily living, and the influencing factors were analyzed by univariate and binary Logistic regression.Results:Among the 431 patients, 260 were male and 171 were female, with an average age of (61.30 ± 9.60) years. The scores of activities of daily living of the patients at baseline, 12 months after enrollment, 36 months after enrollment, and 60 months after enrollment were (5.97 ± 4.30), (7.20 ± 4.61), (8.90 ± 5.60), and (10.57 ± 6.93) points, respectively. The model identified two types of trajectories: rapid decline in low activities of daily living group (25.3%, 109/431) and slow decline in lower activities of daily living group (74.7%, 322/431). The binary Logistic regression results showed that apathy ( OR=0.374, 95% CI 0.189-0.739), fatigue ( OR=0.261, 95% CI 0.138-0.495), University of Pennsylvania Smell Identification Test ( OR=1.039, 95% CI 1.005-1.074), the Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire ( OR=0.880, 95% CI 0.795-0.973), and the gastrointestinal score of the Scales for Outcomes in PD-Autonomic ( OR=0.724, 95% CI 0.630-0.832) were independent influencing factors for the classification of the change trajectory of activities of daily living in patients with Parkinson disease (all P<0.05). Conclusions:Patients with Parkinson disease exhibit a decreasing trend in early activities of daily living, emphasizing the need for targeted interventions in those with fatigue, apathy, and high Rapid Eye Movement Sleep Behavioral Disorder Screening Questionnaire and Scales for Outcomes in Parkinson disease-Autonomic gastrointestinal scores to possibly decelerate disease advancement.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Background::Renal ischemia-reperfusion (R-I/R) injury is the most prevalent cause of acute kidney injury, with high mortality and poor prognosis. However, the underlying pathological mechanisms are not yet fully understood. Therefore, this study aimed to investigate the role of N-myc downstream-regulated gene 2 ( Ndrg2) in R-I/R injury. Methods::We examined the expression of Ndrg2 in the kidney under normal physiological conditions and after R-I/R injury by immunofluorescence staining, real-time polymerase chain reaction, and western blotting. We then detected R-I/R injury in Ndrg2-deficient ( Ndrg2-/-) mice and wild type ( Ndrg2+/+) littermates in vivo, and detected oxygen and glucose deprivation and reperfusion (OGD-R) injury in HK-2 cells. We further conducted transcriptomic sequencing to investigate the role of Ndrg2 in R-I/R injury and detected levels of oxidative stress and mitochondrial damage by dihydroethidium staining, biochemical assays, and western blot. Finally, we measured the levels of mitophagy in Ndrg2+/+ and Ndrg2-/- mice after R-I/R injury or HK-2 cells in OGD-R injury. Results::Ndrg2 was primarily expressed in renal proximal tubules and its expression was significantly decreased 24 h after R-I/R injury. Ndrg2-/- mice exhibited significantly attenuated R-I/R injury compared to Ndrg2+/+ mice. Transcriptomics profiling showed that Ndrg2 deficiency induced perturbations of multiple signaling pathways, downregulated inflammatory responses and oxidative stress, and increased autophagy following R-I/R injury. Further studies revealed that Ndrg2 deficiency reduced oxidative stress and mitochondrial damage. Notably, Ndrg2 deficiency significantly activated phosphatase and tensin homologue on chromosome ten-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy. The downregulation of NDRG2 expression significantly increased cell viability after OGD-R injury, increased the expression of heme oxygenase-1, decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, and increased the expression of the PINK1/Parkin pathway. Conclusion::Ndrg2 deficiency might become a therapy target for R-I/R injury by decreasing oxidative stress, maintaining mitochondrial homeostasis, and activating PINK1/Parkin-mediated mitophagy.

In order to obtain a cell line which high expressed of rabies virus glycoprotein the produc-tion of rabies subunit vaccine,the RABV glycoprotein gene sequence was amplified by RT-PCR and cloned into the lentiviral expression vector.The recombinant plasmid pLV-RVG,envelope plasmid pMD2.0G and packaging plasmid psPAX2 were co-transfected into HEK-293T cells to harvest lentivirus and infect new HEK-293T cells.The 293T-RVG cell line was obtained by puro-mycin pressure screening.Indirect immunofluorescence assay(IFA)and Western blot showed that the 67 kD RABV-G protein was highly expressed in the cells.The neutralizing antibody titer reached 2.19 IU/mL within 14 days after immunization,which was higher than the internationally recognized protection threshold(0.5 IU/mL).This study showed that the cell line 293T-RVG with stable and high expression of rabies virus glycoprotein was successfully constructed.The cell line could protect mice against rabies virus challenge and could be used as a subunit vaccine with poten-tial for large-scale production and application.

Medication is a potential factor influencing frailty. However, the relationship between pharmaceutical treatments and frailty remains unclear. Therefore, we conducted the present systematic review to summarize the association between drug therapy and the risk of incident frailty in older adults. We systematically searched the MEDLINE electronic database for articles indexed between January 1, 2000, and December 31, 2021, for randomized controlled trials (RCTs) and cohort studies reporting frailty changes associated with drug therapy. A total of six RCTs and 13 cohort studies involving 211,948 participants were identified, and their treatments were categorized into six medication classes: analgesics, cardiometabolic medication, chemotherapy, central nervous system (CNS)-active medication, hormonal therapy, and nutritional supplements. While the analysis revealed that only CNS-active medications were associated with an elevated risk of frailty, other medication classes also affected frailty; however, this is not conclusively attributable to a class-wide effect.