[Analysis and summary of clinical characteristics of 289 patients with paroxysmal nocturnal hemoglobinuria in Zhejiang Province].

Objective: To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province. Methods: This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized. Results: Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion: Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Regulation of the expression of casein alpha S1 and S2 genes in the bovine mammary epithelial cells by STAT5A.

Cow milk is rich in protein. Major cow milk proteins include casein α S1 (CSN1S1), casein α S2 (CSN1S2), casein ß (CSN2), casein kappa (CSN3), lactalbumin α (LALBA), and ß-lactoglobulin (LGB). These milk proteins are produced through gene expression in the mammary epithelial cells. Little is known about the molecular mechanism that mediates the expression of milk protein genes in cows. In this study, we tested the hypothesis that the expression of milk protein genes in cows is mediated by STAT5A, a transcription factor that is induced to bind and activate the transcription of target genes by extracellular signals such as prolactin. To circumvent the need of prolactin-responsive bovine mammary epithelial cells, we generated a plasmid that expresses a constitutively active bovine STAT5A variant, bSTAT5ACA. Transfection of the bovine mammary epithelial cell line MAC-T cells with the bSTAT5ACA expression plasmid caused a more than 100,000-fold and 600-fold increase in the expression of CSN1S1 and CSN1S2 mRNAs, respectively, compared with transfection of the wild-type bovine STAT5A (bSTAT5A) expression plasmid. Transfection of bSTAT5ACA, however, had no significant effect on the expression of CSN2, CSN3, LALBA, or LGB mRNA in MAC-T cells. Transfection of bSTAT5ACA caused a more than 260-fold and 120-fold increase in the expression of a luciferase reporter gene linked to the bovine CSN1S1 and CSN1S2 promoters in MAC-T cells, respectively, compared with that of bSTAT5A. The bovine CSN1S1 and CSN1S2 promoters each contain a putative STAT5 binding site, and gel-shift and super-shift assays confirmed bSTAT5ACA binding to both sites. These results together suggest that STAT5A plays a major role in regulating the expression of CSN1S1 and CSN1S2 genes in the bovine mammary epithelial cells and that STAT5A regulates the expression of these genes at least in part by binding to the STAT5 binding sites in their promoter regions. These results also suggest that STAT5A does not play a major role in regulating the expression of other major milk protein genes.

[Association between diabetes prevalence and mortality risk in the elderly aged 60 years and above in Liaoning Province, 2017-2019].

Objective: To investigate the prevalence of diabetes in the elderly aged ≥60 years in Liaoning Province from 2017 to 2019 and analyze the impact of blood glucose control on all-cause mortality and cardiovascular disease (CVD) mortality. Methods: A survey was conducted in the elderly aged ≥60 years in Liaoning from 2017 to 2019 to collect the information about the prevalence of diabetes and other chronic diseases in the diabetes patients. The mortality of the enrolled subjects was investigated in September 2023. Cox proportional hazards regression models were used to estimate the association between blood glucose control in the elderly with diabetes and the risks of all-cause mortality and CVD mortality. Results: The crude prevalence of diabetes in the elderly aged ≥60 years was 20.2% (2 014/9 958) in Liaoning from 2017 to 2019, and the standardized prevalence rate was 19.9%. The prevalence rates of hypertension, dyslipidemia, and overweight/obesity in the diabetes patients were 77.0%, 51.7%, and 67.5% respectively. The median follow-up time was 5.5 years, and the all-cause mortality and CVD mortality rates in the diabetes patients were 244.3/10 000 person-years and 142.9/10 000 person-years, respectively. The results of the Cox proportional hazards regression model analysis showed that compared with non-diabetic individuals, diabetes patients had an increased risk of all-cause mortality by 1.68 times [hazard ratio (HR)=1.68, 95%CI: 1.44-1.94] and an increased risk of CVD mortality by 1.56 times (HR=1.56, 95%CI: 1.29-1.89). The differences in risks of all-cause mortality and CVD mortality between the diabetes patients with normal fasting blood glucose and glycated hemoglobin levels and people without diabetes were not significant (all P>0.05). The failure to meet either the FPG or HbA1c target increased the risk of all-cause mortality (all P<0.05). For individuals who failed to meet the HbA1c target, there was an increased risk of CVD mortality (all P<0.05). Conclusions: The comorbidity rate of chronic diseases was higher in the elderly with diabetes than in the elderly without diabetes in Liaoning. Elderly diabetes patients can benefit from good blood glucose control.

[2, 6-dimethoxy-1, 4-benzoquinone alleviates septic shock in mice by inhibiting NLRP3 inflammasome activation].

OBJECTIVE: To investigate the mechanism of 2, 6-dimethoxy-1, 4-benzoquinone (DMQ), an active ingredients in fermented wheat germ extract, for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice. METHODS: Cultured murine bone marrow-derived macrophages (BMDM) stimulated with lipopolysaccharide (LPS) were treated with DMQ, followed by treatment with Nigericin, ATP, and MSU for activating the canonical NLRP3 inflammasome; the noncanonical NLRP3 inflammasome was activated by intracellular transfection of LPS, and AIM2 inflammasome was activated using Poly A: T.In human monocytic THP-1 cells, the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ, the levels of IL-1ß and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA, and the survival time of the mice within 36 h was observed. RESULTS: Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM, but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock, DMQ treatment significantly reduced the levels of IL-1ß in the serum and peritoneal fluid and obviously prolonged survival time of the mice. CONCLUSION: DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPSinduced septic shock in mice.

[Genetic and clinical characteristics of single and compound types of patients with long QT syndrome type 3].

Objective: To explore the genetic background and clinical features of patients with long QT syndrome type 3 (LQT3). Methods: This retrospective cohort included patients diagnosed with LQT3 at the Department of Cardiology, Renmin Hospital of Wuhan University from January 1998 to December 2022. Patients were categorized into compound type group and single type group based on the presence of a single SCN5A mutation. The two groups were followed up and the differences in baseline characteristics, electrocardiograms, and clinical events between the two groups and probands were compared. Kaplan-Meier curves were used for survival analysis, and the log-rank test was employed to compare the event-free survival rates of first cardiac events between the groups and probands. Results: A total of 97 LQT3 patients were enrolled, including 59 probands. The age at diagnosis was (23.45±19.86) years, with 46 patients (47.4%) being male. Among them, 89 patients were classified as single type group, while 8 patients were classified as compound type group. Genetic testing identified 49 SCN5A mutations, with missense mutations being the majority (91.8%), primarily located in transmembrane regions (40.8%, n=20), interdomain linker regions (28.6%, n=14), and C-terminus (22.4%, n=11). The first cardiac event occurred in 44 patients (45.4%), with an onset age of (13.82±12.50) years. The main trigger was identified as rest or sleep (54.5%, n=24). Compared with patients in single type group, patients in compound type group were younger at diagnosis ((10.35±10.28) years vs. (24.63±20.13) years, P=0.040), had a significantly higher proportion of syncope (87.5% (7/8) vs. 33.7% (30/89), P=0.009), aborted cardiac arrest (62.5% (5/8) vs. 11.2% (10/89), P=0.001), and a lower incidence of event-free survival rates of first cardiac events (12.5% (1/8) vs.58.4% (52/89), log-rank P=0.001). The probands in compound type group had a significantly higher proportion of aborted cardiac arrest comparing to probands in single type group (62.5% (5/8) vs. 17.6% (9/51), P=0.020), while the difference in the incidence rate of event-free survival rates of first cardiac events between the probands in two groups was not statistically significant (12.5% (1/8) vs. 39.2% (20/51), log-rank P=0.08). Conclusion: Compound type LQT3 patients are not uncommon. Such patients are diagnosed at a younger age and exhibit more severe phenotypes, requiring close follow-up and proactive intervention strategies.

[Preliminary study on the role and mechanism of IL-6 receptor antagonists in improving post-infarction ventricular arrhythmia].

Objective: To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism. Methods: The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining. Results: Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP (P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower (P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group (P all<0.05). Conclusions: TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.

[Ultrasonic convex array probe applied to increase success rate of external cephalic version without anesthesia].

Objective: To explore the feasibility of using ultrasonic convex array probe compressing abdominal wall to increase success rate of external cephalic version (ECV) without anesthesia in full-term and near-term pregnancy. Methods: Totally 190 singleton and non-cephalic presentation pregnant women in 36-39+4 weeks of gestation performed ECV from April 2019 to August 2023 in the First Affiliated Hospital of Nanjing Medical University were analyzed. According to whether use the ultrasound probe compressing fetal breech or not, the pregnant women were divided into two groups: 81 cases in the probe-compressing group (including primipara 61 cases and multipara 20 cases) and 109 cases in the non-probe-compressing group(including primipara 72 cases and multipara 37 cases). Clinical data, ECV related factors and complications were analyzed and compared between the two groups. Results: (1) The overall success rate of ECV was 64.2% (122/190). There was no significant difference in the success rate of ECV between probe-compressing group and non-probe-compressing group [69.1% (56/81) vs 60.6% (66/109), χ2=1.490, P=0.222]. The total vaginal delivery rate after successful ECV was 81.1% (99/122), while 71.1% (54/76) in primipara and 97.8% (45/46) in multipara, respectively. (2) Compare to the non-probe-compressing group, the success rate of ECV in primipara was significantly higher in the probe-compressing group [45.8% (33/72) vs 70.5% (43/61)], but the gestational age was shorter and the height was higher in the probe-compressing group (all P<0.05). The success rate of ECV of multipara in the probe-compressing group (65.0%, 13/20) was lower than that in the non-probe-compressing group (89.2%, 33/37), but there was no significant difference between the two groups (P>0.05). (3) Multivariate logistic regression analysis showed that abdominal wall compressed by ultrasound probe (OR=2.601, 95%CI: 1.113-6.075; P=0.027) and amniotic fluid index (AFI; OR=1.010, 95%CI: 1.001-1.020; P=0.028) were positive factors for the successful rate of ECV in primipara pregnant women. (4) The main complication of ECV was transient fetal heart rate reduction (8.9%,17/190), the incidence in the probe-compressing group was significantly higher than that in the non-probe-compressing group [14.8% (12/81) vs 4.6% (5/109); χ2=5.967, P=0.015]. No statistical differences were found in rates of complications between the ECV successful and unsuccessful pregnant women, and between probe-compressing and non-probe-compressing groups (all P>0.05). No adverse maternal and neonatal outcomes related to ECV were observed. Conclusions: The ultrasonic convex array probe compressing could significantly improve the success rate of ECV in primipara without increasing the incidence of adverse maternal and fetal outcomes. The success rate of ECV in primipara is influenced by AFI and operation mode.

[Overexpression of lncRNA FEZF1-AS1 promotes progression of non-small cell lung cancer via the miR-130a-5p/CCND1 axis].

OBJECTIVE: To explore the molecular mechanism by which FEZF1-AS1 overexpression promotes progression of nonsmall cell lung cancer (NSCLC) via the miR-130a-5p/CCND1 axis. METHODS: TCGA database was used to analyze FEZF1-AS1 expression levels in NSCLC. FEZF1-AS1 expression was detected by qRT-PCR in clinical specimens of NSCLC tissues and NSCLC cell lines, and its correlation with clinical features of the patients were analyzed. The binding sites of FEZF1-AS1 with hsa-miR-130a-5p and those of hsa-miR-130a-5p with CCND1 were predicted. CCK8 assay, clone formation assay, scratch assay, and Transwell assay were employed to examine the effects of FEZF1-AS1 knockdown and hsa-miR-130a-5p inhibitor on proliferation, invasion, and migration abilities of lung cancer cell lines. Dual luciferase assay was used to verify the binding of FEZF1-AS1 with hsa-miR-130a-5p and the binding of hsa-miR-130a-5p with CCND1. Western blotting was performed to detect the changes in CCND1 protein expression level in H1299 and H358 cells following FEZF1-AS1 knockdown and treatment with hsa-miR-130a-5p inhibitor. RESULTS: FEZF1-AS1 was highly expressed in NSCLC tissues in close correlation with lymph node metastasis and also in H1299 and H358 cell lines (all P < 0.05). FEZF1-AS1 knockdown obviously reduced proliferation, migration, and invasion abilities of NSCLC cells (P < 0.05). Dual luciferase assay confirmed the binding of hsa-miR-130a-5p with FEZF1-AS1 and CCND1 (P < 0.05), and hsa-miR-130a-5p inhibitor significantly inhibited proliferation, migration, and invasion of NSCLC cells (P < 0.05). FEZF1-AS1 knockdown significantly reduced CCND1 protein expression in NSCLC cells, and this effect was strongly inhibited by treatment with hsa-miR-130a-5p inhibitor (P < 0.05). CONCLUSION: FEZF1-AS1 is highly expressed in NSCLC tissue in close correlation with lymph node metastasis to promote cancer progression through the miR-130a-5p/CCND1 axis.

Rural Hospitals Experienced More Patient Volume Variability Than Urban Hospitals During The COVID-19 Pandemic, 2020-21.

Fluctuations in patient volume during the COVID-19 pandemic may have been particularly concerning for rural hospitals. We examined hospital discharge data from the Healthcare Cost and Utilization Project State Inpatient Databases to compare data from the COVID-19 pandemic period (March 8, 2020-December 31, 2021) with data from the prepandemic period (January 1, 2017-March 7, 2020). Changes in average daily medical volume at rural hospitals showed a dose-response relationship with community COVID-19 burden, ranging from a 13.2 percent decrease in patient volume in periods of low transmission to a 16.5 percent increase in volume in periods of high transmission. Overall, about 35 percent of rural hospitals experienced fluctuations exceeding 20 percent (in either direction) in average daily total volume, in contrast to only 13 percent of urban hospitals experiencing similar magnitudes of changes. Rural hospitals with a large change in average daily volume were more likely to be smaller, government-owned, and critical access hospitals and to have significantly lower operating margins. Our findings suggest that rural hospitals may have been more vulnerable operationally and financially to volume shifts during the pandemic, which warrants attention because of the potential impact on these hospitals' long-term sustainability.

[Immune reconstitution and influencing factors in HIV infected men who have sex with men with access to antiviral therapy in Guangxi Zhuang Autonomous Region from 2005 to 2021].

Objective: To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021. Methods: The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis. Results: A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M (Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m2 and baseline CD4+T lymphocyte (CD4) counts <200 cells/µl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m2 and baseline CD4 counts ≥200 cells/µl were more likely to have complete immune reconstitution. Conclusions: In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.

Two-Stage Treatment Protocol of Fungal Periprosthetic Hip and Knee Joint Infections: the Clinical Experience from a Single Center Experience.

PURPOSE OF THE STUDY: To evaluate the clinical results and safety of fungal periprosthetic joint Infections (fPJIs) using two-stage treatment protocol. MATERIAL AND METHODS: 8 patients with fPJIs (3 hips and 5 knees) using two-stage revision were reviewed retrospectively and followed up at least 2 years. The preoperative demographic data, two-stage treatment protocol, results of microbiology and histologic workup and postoperative follow-up results (reimplantation success rate and infection free time) were recorded. RESULTS: 7 patients got successful reimplantation, with a 75% reimplantation success rate. Two patients got knee arthrodesis eventually. All patients were infection free with a median follow-up of 4.0 ± 2.0 years (range, 2-7 years). Of them, Candida species were found in 7 patients, while non-Candida specimen was only isolated in 1 patient with Aspergillus. Only 2 patients had coexisting bacterial infection (Methicillin-resistant coagulase-negative Staphylococci and Proteus mirabilis respectively). The average interval between the initial surgery and diagnosis of fPJIs was 21.50±34.79 months (range, 4-104 months). The mean time of spacer implantation was 7.75±2.77 months (range, 6-14 months). None serious complication or above knee amputation was found. DISCUSSION: fPJIs are very rare and considerable challenge after total hip or knee arthroplasty. The goal of therapy is to eradicate local infection and maintain function. Candida species were the most common pathogen. The duration between spacer placement and staged reimplantation was highly variable, and generally dependent upon the results of joint aspirates and infl ammatory markers. The current study shows that the two-stage treatment protocol is recommended for fungal periprosthetic hip and knee joint infections. CONCLUSIONS: The two-stage treatment protocol is recommended for fungal periprosthetic hip and knee joint infections. The safety and effi cacy of biantibiotical impregnated (antifungal + antibiotics) cement spacer is confi rmed. Further evidence-based work is needed to determine the optimal drug dose and reimplantation time. KEY WORDS: two-stage treatment protocol, fungal periprosthetic infections, hip spacer, knee spacer.

Mortality for Time-Sensitive Conditions at Urban vs Rural Hospitals During the COVID-19 Pandemic.

Importance: COVID-19 pandemic-related disruptions to the health care system may have resulted in increased mortality for patients with time-sensitive conditions. Objective: To examine whether in-hospital mortality in hospitalizations not related to COVID-19 (non-COVID-19 stays) for time-sensitive conditions changed during the pandemic and how it varied by hospital urban vs rural location. Design, Setting, and Participants: This cohort study was an interrupted time-series analysis to assess in-hospital mortality during the COVID-19 pandemic (March 8, 2020, to December 31, 2021) compared with the prepandemic period (January 1, 2017, to March 7, 2020) overall, by month, and by community COVID-19 transmission level for adult discharges from 3813 US hospitals in the State Inpatient Databases for the Healthcare Cost and Utilization Project. Exposure: The COVID-19 pandemic. Main Outcomes and Measures: The main outcome measure was in-hospital mortality among non-COVID-19 stays for 6 time-sensitive medical conditions: acute myocardial infarction, hip fracture, gastrointestinal hemorrhage, pneumonia, sepsis, and stroke. Entropy weights were used to align patient characteristics in the 2 time periods by age, sex, and comorbidities. Results: There were 18 601 925 hospitalizations; 50.3% of patients were male, 38.5% were aged 18 to 64 years, 45.0% were aged 65 to 84 years, and 16.4% were 85 years or older for the selected time-sensitive medical conditions from 2017 through 2021. The odds of in-hospital mortality for sepsis increased 27% from the prepandemic to the pandemic periods at urban hospitals (odds ratio [OR], 1.27; 95% CI, 1.25-1.29) and 35% at rural hospitals (OR, 1.35; 95% CI, 1.30-1.40). In-hospital mortality for pneumonia had similar increases at urban (OR, 1.48; 95% CI, 1.42-1.54) and rural (OR, 1.46; 95% CI, 1.36-1.57) hospitals. Increases in mortality for these 2 conditions showed a dose-response association with the community COVID-19 level (low vs high COVID-19 burden) for both rural (sepsis: 22% vs 54%; pneumonia: 30% vs 66%) and urban (sepsis: 16% vs 28%; pneumonia: 34% vs 61%) hospitals. The odds of mortality for acute myocardial infarction increased 9% (OR, 1.09; 95% CI, 1.06-1.12) at urban hospitals and was responsive to the community COVID-19 level. There were significant increases in mortality for hip fracture at rural hospitals (OR, 1.32; 95% CI, 1.14-1.53) and for gastrointestinal hemorrhage at urban hospitals (OR, 1.15; 95% CI, 1.09-1.21). No significant change was found in mortality for stroke overall. Conclusions and Relevance: In this cohort study, in-hospital mortality for time-sensitive conditions increased during the COVID-19 pandemic. Mobilizing strategies tailored to the different needs of urban and rural hospitals may help reduce the likelihood of excess deaths during future public health crises.

[Analyses of the risk factors for the progression of primary antiphospholipid syndrome to systemic lupus erythematosus].

Objectives: Analyze the clinical characteristics of patients with primary antiphospholipid syndrome (PAPS) progressing to systemic lupus erythematosus (SLE).Explore the risk factors for the progression from PAPS to SLE. Methods: The clinical data of 262 patients with PAPS enrolled in Peking Union Medical College Hospital from February 2005 to September 2021 were evaluated. Assessments included demographic data, clinical manifestations, laboratory tests (serum levels of complement, anti-nuclear antibodies, anti-double-stranded DNA antibodies), treatment, and outcomes. Kaplan-Meier analysis was used to calculate the prevalence of SLE in patients with PAPS. Univariate Cox regression analysis was employed to identify the risk factors for PAPS progressing to SLE. Results: Among 262 patients with PAPS, 249 had PAPS (PAPS group) and 13 progressed to SLE (5.0%) (PAPS-SLE group). Univariate Cox regression analysis indicated that cardiac valve disease (HR=6.360), positive anti-double-stranded DNA antibodies (HR=7.203), low level of complement C3 (HR=25.715), and low level of complement C4 (HR=10.466) were risk factors for the progression of PAPS to SLE, whereas arterial thrombotic events (HR=0.109) were protective factors (P<0.05 for all). Kaplan-Meier analysis showed that the prevalence of SLE in patients suffering from PAPS with a disease course>10 years was 9%-15%. Hydroxychloroquine treatment had no effect on the occurrence of SLE in patients with PAPS (HR=0.753, 95%CI 0.231-2.450, P=0.638). Patients with≥2 risk factors had a significantly higher prevalence of SLE compared with those with no or one risk factor (13-year cumulative prevalence of SLE 48.7% vs. 0 vs. 6.2%, P<0.001 for both). Conclusions: PAPS may progress to SLE in some patients. Early onset, cardiac-valve disease, positive anti-dsDNA antibody, and low levels of complement are risk factors for the progression of PAPS to SLE (especially in patients with≥2 risk factors). Whether application of hydroxychloroquine can delay this transition has yet to be demonstrated.

[Efficacy and safety of first-line treatment with anti-CD38 monoclonal antibody-based regimen for primary plasma cell leukemia].

Objective: To analyze the efficacy and safety of first-line treatment with an anti-CD38 monoclonal antibody regimen for primary plasma cell leukemia (pPCL). Methods: Patients diagnosed with pPCL from December 1st, 2018 to July 26th, 2023, receiving first-line treatment of anti-CD38 monoclonal antibody-based regimens across multiple centers including Peking University People's Hospital, Fuxing Hospital of Capital Medical University, Qingdao Municipal Hospital, Shengjing Hospital of China Medical University, Handan Central Hospital, the First Affiliated Hospital of Harbin Medical University, the Fourth Hospital of Hebei Medical University and General Hospital of Ningxia Medical University were consecutively included. A total of 24 pPCL patients were included with thirteen being male and eleven being female. The median age [M(Q1, Q3)] was 60 (57, 70) years. Patients were grouped according to peripheral blood plasma cell (PBPC) percentage [5%-19% (n=14) vs ≥20% (n=10)]. Last follow-up date was September 26th, 2023. The median follow-up period was 9.1 (4.2, 15.5) months. Patients' data related with clinical baseline characteristics, efficacy, survival and safety were retrospectively collected. Cox proportional hazards regression model was used to analyze risk factors associated with survival. Results: Among 24 pPCL patients, 16 (66.7%) patients had anemia at diagnosis, 13(54.2%) patients had thrombocytopenia, 8 (33.3%) patients had a baseline estimated glomerular filtration rate (eGFR)<40 ml·min-1·(1.73m2)-1, 13 (54.2%) patients had elevated lactate dehydrogenase (LDH) levels. The median PBPC percentage was 16% (8%, 26%) . Fluorescence in situ hybridization testing indicated that patients harboring 17p deletion, t(4;14) or t(14;16) were 6 (25.0%), 4 (16.7%) and 4 (16.7%), respectively. The overall response rate was 83.3% (20/24). The median progression-free survival (PFS) was 20.5 (95%CI: 15.8-25.2) months, and the median overall survival (OS) was not reached. Estimated 1-year and 2-year PFS and OS rates were 75.0% and 89.1%, 37.5% and 53.4%, respectively. The median PFS and OS for patients with PBPC percentages 5%-19% and≥20% were not reached and 20.5 (95%CI:15.7-25.3) months, 17.8 months and not reached, respectively. There was no significant statistical difference of PFS and OS between two groups (all P>0.05). Multivariate Cox regression analysis showed that 1p32 deletion was the risk factor associated with PFS (HR=7.7, 95%CI: 1.1-54.9, P=0.043). Seventeen patients (70.8%) developed grade 3-4 hematologic toxicities. Twelve patients (50.0%) developed grade 3-4 thrombocytopenia. Sixteen patients (66.7%) developed infection. All hematologic toxicities and infections were improved after supportive treatment. Conclusion: First-line treatment with anti-CD38 monoclonal antibody-based therapy for pPCL is effective and safe.

Serum fibroblast growth factor-2 levels complement vital biomarkers for diagnosing heart failure.

BACKGROUND: Early diagnosis of atrial fibrillation is important as it is crucial for improving patient outcomes. Fibroblast growth factor-2 (FGF2) may serve as a diagnostic biomarker for heart failure due to its ability to promote cardiac fibrosis and hypertrophy; however, the relationship between FGF2 concentration and heart failure is unclear. Therefore, this study aimed to explore whether FGF2 could aid in distinguishing patients with heart failure from healthy controls and those with dyspnea without heart failure. Additionally, to evaluate the possible correlation between serum FGF2 levels and its diagnostic parameters in patients with heart failure. METHODS: Plasma FGF2 concentration was measured in 114 patients with a complaint of dyspnea (enrolled in the study between January 2022 and August 2022). Based on heart failure diagnosis, the patients were assigned to three groups, as follows: heart failure (n = 80), non-heart-failure dyspnea (n = 34), and healthy controls (n = 36), following physical examination. Possible correlations between serum FGF2 levels and other prognostic parameters in patients with heart failure were analyzed. RESULTS: Serum FGF2 levels were higher in patients with heart failure (125.60 [88.95, 183.40] pg/mL) than in those with non-heart-failure dyspnea (65.30 [28.85, 78.95] pg/mL) and healthy controls (78.90 [60.80, 87.20] pg/mL) (p < 0.001). Receiver operating characteristic curve analysis identified FGF2 concentration as a significant predictor in heart failure diagnosis, with an area under the curve of 0.8693 (p < 0.0001). Importantly, in the heart failure group, serum FGF2 concentrations correlated with key prognostic parameters for heart failure, such as reduced left ventricular ejection fraction and elevated serum levels of N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: Elevated serum FGF2 level is strongly associated with an increased risk of heart failure and could serve as a useful biomarker to complement vital diagnostic parameters for heart failure.

[Prevalence of medicare antiviral drugs use and related factors in HIV-infected people in Ningbo].

Objective: To analyze the use of medicare antiviral drugs (ART) and related factors among HIV-infected people in Ningbo City. Methods: The retrospective data was collected related to infection and treatment of HIV-infected people in ART in Ningbo up to February 2023 through the National Infectious Disease Surveillance System. Binary logistic regression was used to analyze the factors related to medicare antiviral drug use in HIV-infected people. R 4.2.2 software was used for statistical analysis. Results: A total of 6 433 HIV-infected people with ART records were collected, among which 5 783 were in ART. The prevalence of medicare drugs use among people in ART was 24.8% (1 435/5 783, 95%CI: 23.7%-25.9%). Beilun District (8.7%, 43/497) and Fenghua District (5.7%, 14/247) had the lowest level in medicare drugs use. Among people in ART using medicare or out-of-pocket drugs, the prevalence of those who had at least one viral load test in the last year (84.9%, 1 352/1 593) was significantly lower than that of those using free drugs (91.4%, 3 829/4 190) (χ2=52.50, P<0.001). The results of multivariate logistic analysis showed that the factors influencing medicare drug use included low educational level (junior high school and below: aOR=0.24, 95%CI:0.17-0.34), farmer or worker (farmer: aOR=0.60, 95%CI: 0.39-0.91; worker: aOR=0.42, 95%CI: 0.27-0.64), low monthly income (<3 000 Yuan: aOR=0.29, 95%CI: 0.18-0.45), the longer interval time between diagnosis and treatment (≥21 days: aOR=0.47, 95%CI: 0.30-0.74). Conclusions: Significant regional differences on the prevalence of medicare antiviral drugs use in HIV-infected people exist in Ningbo City. Follow-up management program of patients should be improved to strengthen patient compliance to mobilize medicare drug promotion. Meanwhile, publicity of medicare drugs should be strengthened for farmers or workers with low education level and patients with delayed treatment.

Lacticaseibacillus rhamnosus GG Improves Periodontal Bone Repair via Gut-Blood Axis in Hyperlipidemia.

Periodontal bone regeneration remains a clinical challenge, and hyperlipidemia can aggravate alveolar bone resorption. Probiotics have recently been reported to improve bone mass. We aimed to determine the role of Lacticaseibacillus rhamnosus GG (LGG) in periodontal bone regeneration improvement within the context of periodontitis with hyperlipidemia. A Sprague Dawley rat model for periodontitis, hyperlipidemia, and periodontal fenestration defect was constructed (n = 36) and administered LGG gavage for 6 wk (the rats were subsequently sacrificed). Fecal microbiota from donor rats 3 wk after LGG gavage was transplanted into recipient rats to evaluate the role of LGG-modulated gut microbiota in periodontal bone regeneration. Regenerated bone mass was detected using micro-computerized tomography and hematoxylin and eosin stain. Gut microbiota was analyzed using 16S ribosomal RNA sequencing. Serum metabolites were detected by liquid chromatography-mass spectrometry (6 wk after LGG gavage). The pro-osteogenic effects of screened serum metabolite were verified in vitro on bone marrow mesenchymal stem cells (BMMSCs). We found that the bone mineral density, bone volume (BV), trabecular bone volume fraction (BV/TV), and trabecular thickness of the regenerated periodontal bone increased after LGG gavage (P < 0.05) but had little effect on oral flora. After LGG gavage, Staphylococcus, Corynebacterium, and Collinsella in the gut of donors were significantly changed, and these differences were maintained in recipients, who also showed increased trabecular thickness of the regenerated periodontal bone (P < 0.05). These key genera were correlated with BV/TV and BV (P < 0.05). In addition, LGG gavage significantly regulated bone-related blood metabolites, of which selenomethionine promoted BMMSC osteogenesis. Notably, selenomethionine was associated with key gut genera (P < 0.05). Collectively, LGG improved periodontal bone regeneration in the context of periodontitis with hyperlipidemia by modulating gut microbiota and increasing pro-osteogenic metabolites in the blood. These results reveal new insights into the use of probiotics to promote periodontal bone regeneration via the gut-blood-bone axis.