Rationale for issuing neuroimaging requests for patients with primary headaches in China.

OBJECTIVE: To investigate the prevalence of neuroimaging in patients with primary headaches and the clinician-based rationale for requesting neuroimaging in China. DATA SOURCES AND STUDY SETTING: This study included patients with primary headaches admitted to hospitals and clinicians in China. We identified whether neuroimaging was requested and the types of neuroimaging conducted. STUDY DESIGN: This was a cross-sectional study, and convenience sampling was used to recruit patients with primary headaches. Clinicians were interviewed using a combination of personal in-depth and topic-selection group interviews to explore why doctors requested neuroimaging. DATA COLLECTION: We searched for the diagnosis of primary headache in the outpatient and inpatient systems according to the International Classification of Diseases-10 code of patients admitted to six hospitals in three provincial capitals by 2022.We selected three public and three private hospitals with neurology specialties that treated a corresponding number of patients. PRINCIPLE FINDINGS: Among the 2263 patients recruited for this study, 1942 (89.75%) underwent neuroimaging. Of the patients, 1157 (51.13%) underwent magnetic resonance imaging (MRI), 246 (10.87%) underwent both head computed tomography (CT) and MRI, and 628 (27.75%) underwent CT. Fifteen of the 16 interviewed clinicians did not issue a neuroimaging request for patients with primary headaches. Furthermore, we found that doctors issued a neuroimaging request for patients with primary headaches mostly, to exclude the risk of misdiagnosis, reduce uncertainty, avoid medical disputes, meet patients' medical needs, and complete hospital assessment indicators. CONCLUSIONS: For primary headaches, the probability of clinicians requesting neuroimaging was higher in China than in other countries. There is considerable room for improvement in determining appropriate strategies to reduce the use of low-value care for doctors and patients.

The predictive value of PI3K signaling pathway in ovarian cancer prognosis: a meta-analysis.

OBJECTIVE: The aim of the study was to comprehensively assess the clinical significance of the Phosphoinositide 3-kinase (PI3K) signaling pathway in ovarian cancer patients, we conducted a meticulous meta-analysis utilizing individual studies. MATERIALS AND METHODS: In this meta-analysis, publications through PubMed, Embase, and Cochrane Library databases were searched from inception to December 2022. In this study, only published studies related to the PI3K signaling pathway and prognosis of ovarian cancer patients were included, excluding unpublished literature, incomplete data, animal experiments, literature reviews, and systematic studies. All data were processed by STATA15.1 statistical software. RESULTS: Previous studies found that PI3K activation was closely related to poor prognosis of ovarian cancer cells [Hazard Ratio (HR)=1.67, 95% CI: 1.03-2.69, p=0.038], but not significantly related to disease-free prognosis (HR=1.07, 95% CI: 0.12-9.54, p=0.950). Our previous study found that PI3K pathway activation significantly reduced survival in >50% of stage II/III ovarian cancer cells (HR=2.07, 95% CI: 1.17-3.66, p=0.012). Our previous study found that PI3K activation level was not strongly associated with the survival of osteosarcoma in the European population (HR=1.35, 95% CI: 0.24-7.60, p=0.733), while in the Asian population, PI3K activation level was not strongly associated with the survival of osteosarcoma (HR=1.47, 95% CI: 1.15-1.87, p=0.023). CONCLUSIONS: PI3K can be used as a predictor of prognosis for ovarian cancer, especially in advanced ovarian cancer and Asian patients. Activation of PI3K signaling is associated with poor prognosis in ovarian cancer.

[Multiple primary tumors in children: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.

[Efficacy of sutureless intrascleral intraocular lens fixation with the modified Yamane technique].

Objective: To evaluate the efficacy of sutureless intrascleral intraocular lens (IOL) fixation with the modified Yamane technique. Methods: It was a retrospective case series study. Patients undergoing sutureless intrascleral IOL fixation with the modified Yamane technique were included at Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University from January 2022 to September 2023. Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), recorded as the logarithm of the minimum angle of resolution (logMAR), were measured before surgery and at 1 day, 3 days, 1 week, 1 month, and 3 months postoperatively. Refractive error and intraocular pressure were also checked. Anterior segment examination with a slit lamp microscope, fundus examination, anterior segment and posterior segment optical coherence tomography were performed. Intraoperative and postoperative ocular complications were documented. Results: A total of 53 patients (53 eyes) were included in this study, comprising 40 males and 13 females, with a median age of 60 (49, 68) years. Among them, the proportion of a history of trauma was 22.6% (12/53). There was 1 eye with intraoperative vitreous hemorrhage (1.9%). All eyes had no obvious hypotony, no obvious inflammation in the anterior chamber, and no pupillary abnormalities at 1 week after surgery. The mean follow-up time was (8.0±3.3) months (range, 3 to 16 months). There was no iris capture, re-dislocation, or haptic exposure of the IOL during the follow-up. The corneal endothelial cell density was (2 236±704) cells/mm2 preoperatively and (1 964±628) cells/mm2 at 1 month, with significant difference (P<0.001). The UCVA (logMAR) was 1.53±0.75 preoperatively, 0.18±0.17 at 1 month, 0.15±0.14 at 3 months, and 0.14±0.13 at the final visit (P<0.001). The UCVA (logMAR) at 1 month was significantly different from that at 3 months and the final visit (both P<0.05). At 1 month, 50.9% (27/53) of the eyes had an UCVA (logMAR)≤0.1, and the rate was 56.6% (30/53) at 3 months. The BCVA (logMAR) was 0.25±0.21, 0.03±0.06, 0.02±0.06, and 0.02±0.06 before surgery, at postoperative1 month, 3 months, and the final visit, respectively (P<0.001). The BCVA (logMAR) at 1 month was not significantly different from that at 3 months and the final visit (both P>0.05). The rate of the eyes with a BCVA (logMAR)≤0 was 81.1% (43/53) at 1 month and 83.0% (44/53) at 3 months. The IOL tilt was (5.18±2.60)° at postoperative 1 month and (5.08±2.48)° at postoperative 3 months, without statistically significant difference (P>0.05). The IOL decentration was (0.35±0.24) mm at postoperative 1 month and (0.32±0.24) mm at postoperative 3 months, without statistically significant difference (P>0.05). Conclusion: Sutureless intrascleral IOL fixation with the modified Yamane technique is simpler and more minimally invasive to achieve a stable and centered IOL implantation with fewer complications and good visual prognosis.

[Distribution and influencing factors of lipoprotein (a) levels in non-arteriosclerotic cardiovascular disease population in China].

Objective: To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors. Methods: This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels. Results: Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M (Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) (OR=1.23, 95%CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced (OR=0.68, 95%CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95%CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95%CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95%CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95%CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions: Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.

[Current status of tuberculosis burden in China].

Tuberculosis, caused by Mycobacterium tuberculosis, is an infectious disease that most often affects the lungs. China is still among the high-burden tuberculosis countries in the world. Although the estimated incidence of tuberculosis in China has declined in recent years, the declining rate is slow. It still faces major issues such as a slower rate of decline, a widening gap between estimated and notified incidence, higher risk among middle-aged and older adults, a high number of cases among agriculture and related workers, and a heavier disease burden in the country's western regions. In addition, latent tuberculosis infection, drug-resistant tuberculosis, tuberculosis coinfection with HIV, and extrapulmonary tuberculosis have also exacerbated the disease burden of tuberculosis to some extent. This paper reviewed the epidemic characteristics of tuberculosis, the epidemiological triad, three links and two factors in the transmission process, the disease burden, and other aspects to provide a reference for formulating prevention and control strategies on tuberculosis.

[Progress in research of relationship between marital status and cancer].

In recent 30 years, the global burden of cancer has become more serious, and one of social problem is population aging, plus declining birth rate, declining marriage rate and increasing divorce rate. Marriage is one of the most intimate and long-term social relations, and previous research had piecemeal reports of its impact on cancer morbidity and mortality without systematic review of evidence in high-quality population based epidemiological research. This paper summarizes the progress in research of the relationship between marital status and cancer to provide reference for future research and cancer prevention and control.

Adherence to guidelines and central-line-associated bloodstream infection occurrence during insertion and maintenance of intravascular catheters: evidence from 20 tertiary hospitals.

OBJECTIVE: To investigate adherence to intravascular catheter (IVC) insertion and maintenance guidelines in Chinese tertiary hospitals. METHODS: A cross-sectional questionnaire survey of adult inpatients with IVC placements was conducted from July to September 2022 in 20 tertiary hospitals in China. One clinical staff member from each department in each hospital was assigned to participate in the survey. Questionnaires were uniformly collected and reviewed after three months. RESULTS: This study included 1815 cases (62.69%) of central venous catheter, 471 cases (16.27%) of peripherally inserted central catheter, 461 cases (15.92%) of PORT, and 147 cases (5.08%) of haemodialysis catheter insertions. Statistically significant differences in compliance were observed across the four IVC types, specifically in relation to the insertion checklist, standard operating procedure, and insertion environment (P<0.05). Practice adherence during IVC maintenance differed significantly across the four IVC types in aspects such as availability of IVC maintenance verification forms, daily scrubbing of the catheterized patients, and catheter connection methods (P<0.05). A total of 386 (13.34%) patients developed fever, 1086 (37.53%) were treated with therapeutic antibiotics, 16 (0.55%) developed central-line-associated bloodstream infections, two (0.07%) developed local skin infections, and six (0.21%) developed deep vein thrombosis. CONCLUSIONS: Adherence to guidelines regarding insertion and maintenance differed across the four IVC types; there is a gap between the recommended measures and the actual operation of the guidelines. Therefore, it is necessary to further enhance training and develop checklists to prevent central-line-associated bloodstream infections.

[An observational and Mendelian randomization study of the associations of body mass index with plasma amino acids and acylcarnitines in Chinese adults].

Objective: To explore the relationship between BMI and levels of plasma amino acids and acylcarnitines in Chinese adults. Methods: Based on 2 182 individuals with targeted mass spectrometry metabolomic measurements from the first resurvey of the China Kadoorie Biobank, we assessed the linear and nonlinear associations between BMI and plasma levels of 20 amino acids and 40 acylcarnitines using linear regression models and restricted cubic spline models, and identified BMI-related metabolic pathways. We conducted one-sample Mendelian randomization (MR) with BMI genetic risk scores as the instrumental variable further to explore the potential causal relationships between BMI and 20 amino acids and 40 acylcarnitines, and tested for horizontal pleiotropy using the MR-Egger method. Results: Observational analyses found that BMI was associated with increased plasma levels of 3 branched-chain amino acids (isoleucine, leucine, and valine), 2 aromatic amino acids (phenylalanine and tyrosine), 3 other amino acids (cysteine, glutamate, lysine), and 7 acylcarnitines (C3, C4, C5, C10, C10:1, C14, and C16), and with decreased circulating levels of asparagine, serine, and glycine. Pathway analysis identified 7 BMI-related amino acids metabolic pathways (false discovery rate corrected all P<0.05), including branched-chain amino acids and aromatic amino acids biosynthesis, glutathione metabolism, etc. BMI showed a nonlinear relationship with leucine, valine, and threonine, and a linear relationship with other amino acids and acylcarnitines. One-sample MR analyses revealed that BMI was associated with elevated levels of tyrosine and 4 acylcarnitines [C5-DC(C6-OH), C5-M-DC, C12-DC, and C14], with tyrosine and acylcarnitine C14 positively correlated with BMI in both observational [the ß values (95%CIs) were 0.057 (0.044-0.070) and 0.018 (0.005-0.032), respectively] and One-sample MR analyses [the ß values (95%CIs) were 0.102 (0.035-0.169) and 0.104 (0.036-0.173), respectively]. The MR analyses of the current study satisfied the 3 core assumptions of instrumental variable. Conclusions: BMI was associated with circulating 11 amino acids and 7 acylcarnitines in Chinese adults, involving several pathways such as branched-chain amino acid and aromatic amino acid metabolism, fatty acid metabolism, and oxidative stress. There may be a causal relationship between BMI and tyrosine and acylcarnitine C14.

[The impact of non-HDL-C level on major adverse cardiovascular and cerebrovascular events and all-cause mortality after revascularization].

Objective: To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization. Methods: This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes. Results: A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [HR=0.62(95%CI: 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [HR=0.80(95%CI: 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P<0.001, non-linear association P=0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95%CI: 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [HR=0.85(95%CI: 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P=0.039, non-linear association P=0.174). Conclusion: The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.

Modulation of the microRNA-6089/E2F transcription factor2 axis by querceting: implications for osteoblast viability, proliferation, migration, and osteogenic differentiation in fracture healing.

Quercetin is widely distributed in plants as a flavonol compound with multiple biological activities. It has been found that quercetin can regulate bone homeostasis through multiple pathways and targets. This study investigated the role and specific molecular mechanisms of quercetin in regulating osteoblast viability, proliferation, migration and osteogenic differentiation. A mouse model of traumatic fracture was established and then 100 mg/kg quercetin corn oil suspension was gavaged at the same time every day for 28 days. miR-6089 and E2F transcription factor 2 (E2F2) expression levels in mice were measured. Fracture healing in mice was observed. MC3T3-E1 cells were transfected with plasmids targeting miR-6089 and E2F2, and cell viability, proliferation, migration, apoptosis, and osteogenic differentiation were determined. The targeting relationship between miR-6089 and E2F2 was verified. In vivo experiments showed that quercetin significantly increased osteocalcin (OCN) expression (P<0.05) and promoted fracture healing in traumatic fracture (TF) mice. miR-6089 expression was down-regulated (P<0.05) and E2F2 expression was up-regulated (P<0.05) in TF mice. Quercetin promoted miR-6089 expression and inhibited E2F2 expression (both P<0.05). In vitro results showed that quercetin promoted miR-6089 expression and inhibited E2F2 expression in a dose-dependent manner (both P<0.05). Quercetin dose-dependently promoted MC3T3-E1 cell viability, proliferation, migration, and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). Up-regulating miR-6089 further promoted MC3T3-E1 cell viability, proliferation, migration and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). miR-6089 targeted and regulated E2F2 expression. Up-regulating E2F2 attenuated the promoting effect of up-regulated miR-6089 on MC3T3-E1 cell viability, proliferation, migration, osteogenic differentiation, and inhibition of apoptosis (all P<0.05). We conclude that quercetin enhances osteoblast viability, proliferation, migration, and osteogenic differentiation by modulating the miR-6089/E2F2 axis, thereby promoting fracture healing.

[Fabrication of a coral-like barium titanate nano-piezoelectric coating and its effect on promoting osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro].

Objective: To investigate the biocompatibility of coral-like barium titanate nano-piezoelectric coatings and the influence of ultrasound-excited piezoelectric effect on the early osteogenic differentiation. Methods: The barium titanate nano-piezoelectric coating (the coating group) was prepared on the surface of titanium metal by anodic oxidation, hydrothermal reaction and high-temperature annealing, and polished titanium specimens were used as control group. The surface morphology, composition, and crystal phase and hydrophilicity of the two groups of titanium specimens were characterized using scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy and contact angle meter. The piezoelectric properties of the materials were characterized by piezoresponse force microscopy. Rat bone marrow mesenchymal stem cells (BMSC) were cultured and identified and seeded the surface of titanium specimens in two groups. The cells seeded on blank culture plates were used as blank group. After low intensity pulsed ultrasound intervention, cell proliferation and live/dead staining were detected to evaluate cytocompatibility of the coatings. Alkaline phosphatase (ALP) activity of each group was detected by ALP staining kit, and the expression of osteogenesis-related genes [integrin, bone morphogenetic protein 2 (BMP-2), Runt-related transcription factor 2 (RUNX2)] was detected by real-time fluorescent quantitative PCR (RT-qPCR) to evaluate the effect of the coating on promoting the early osteogenic differentiation of BMSC. Results: The surface of titanium specimens in the coating group showed a uniform coral-like morphology, and the diameter of the coral tentacles was 70-100 nm. The main component was tetragonal barium titanate. The surface hydrophilicity of the coating group (water contact angle 10.12°± 0.93°) was significantly better than that of the control group (water contact angle 78.32°±0.71°) (F= 10 165.91, P<0.001). The coating has a stable piezoelectric property with a piezoelectric constant of about 5 pC/N. Cell experiments showed that, with or without ultrasound, the cell proliferation activity of the coating group was significantly lower than that of the blank group and the control group on the third day (P<0.05). On the fifth day, with or without ultrasound, there was no significant difference in cell proliferation activity between the three groups (P>0.05). After 7 days of culture, the ALP activity of the coating group was significantly higher than that of the blank group and the control group (P<0.05). The results of RT-qPCR showed that the mRNA expression of integrin and BMP-2 in the coating group with ultrasound was significantly higher than that in the other groups with ultrasound, and was higher than that of the coating group without ultrasound (P<0.05). The expression of integrin mRNA in the control group with ultrasound was significantly higher than that in the control group without ultrasound (P<0.05). The expression of RUNX2 mRNA in the coating group with ultrasound was significantly higher than that in the coating group without ultrasound (P<0.05). Conclusions: The coral-like barium titanate nano-piezoelectric coating exhibits favorable biocompatibility and stable piezoelectric property, and facilitates the early osteogenic differentiation of BMSC under the excitation of low-intensity pulsed ultrasound.

[Correlation and mechanism between chronic kidney disease and periodontitis based on cross-sectional data].

Objective: To explore the correlation between periodontitis (PD) and chronic kidney disease (CKD) in adults, as well as the potential mechanisms involved. Methods: Data on PD and CKD from the National Health and Nutrition Examination Survey (NHANES) database between 1999 and 2014 were downloaded. Weighted univariate and multivariate logistic regression analyses were conducted to investigate the risk factors associated with PD and CKD, considering demographic and clinical indicators. Using publicly available genome-wide association study (GWAS) summary datasets for CKD and PD as outcome variables, as well as 731 immune cell phenotypes and 91 inflammatory proteins as exposure factors from the OPEN GWAS database, a two-sample Mendelian randomization (TSMR) analysis was performed using the inverse-variance weighted (IVW) method. Results: Seven demographic indicators including gender, age, race, education level, marital status, income, and health are related to the incidence of CKD and PD. Among them, the elderly (≥60 years old), poverty (poverty-income ratio <1.3), divorce or widowhood, and male ratio in the comorbidity group of CKD and PD [67.12% (833/1 241), 36.83% (457/1 241), 34.41% (427/1 241), and 57.78% (717/1 241) respectively] were significantly higher than those in the control group [23.71% (4 179/17 623), 29.17% (5 141/17 623), 18.16% (3 200/17 623), and 48.73% (8 587/17 623) respectively] (all P<0.001). Those with high educational level (university and above) and self-rated excellent health accounted for a relatively small proportion in the comorbidity group [14.10% (175/1 241) and 8.22% (102/1 241) respectively]. The prevalence of PD increased among individuals with abnormal renal function indices, including glomerular filtration rate, urine protein/creatinine ratio, serum creatinine, serum uric acid, and blood urea nitrogen. Univariate logistic regression analysis showed a positive correlation between the incidence of PD and CKD (OR=2.14, 95%CI: 1.90-2.42, P<0.001). Multivariate logistic regression analysis also indicated that PD and CKD were potential risk factors for each other (PD for CKD: OR=1.22, 95%CI: 1.07-1.40, P=0.004; CKD for PD: OR=1.19, 95%CI: 1.04-1.37, P=0.012). Furthermore, after adjusting the model based on demographic indicators, there was still a significant correlation between PD and CKD (P=0.010). Mechanistically, the results of the TSMR analysis support the existence of a common risk factor mediated by immune cells between CKD and PD, namely the expression of CD64 on multiple innate immune cells mediates the occurrence of CKD and PD. The absolute count of CD64+ monocytes is associated with an increased risk for both CKD (HR=1.11) and PD (HR=1.07), while same tendency showed in the absolute count of CD64+ neutrophils for CKD (HR=1.22) and PD (HR=1.23). Conclusions: There is a positive correlation between CKD and PD, particularly moderate to severe PD, and the shared pathogenesis involves CD64+ monocytes in the circulatory system. Targeted interventions focusing on CD64 molecules or monocyte subsets may be beneficial.

[Efficacy and safety of eltrombopag in the treatment of primary immune thrombocytopenia: real-world data from a single medical center].

Objective: This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects. Methods: A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments. Results: Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively (P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively (P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% (P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion: Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

[Retrospective analysis of diagnosis and treatment of tuberculosis in designated medical institutions in China from 2017 to 2022].

Objective: To understand the status of tuberculosis diagnosis and treatment capacity and the development and changes of tuberculosis diagnosis and treatment in provincial and municipal designated medical institutions in China from 2017 to 2022, so as to provide a basis for the formulation of relevant policies for the improvement and development of designated medical institutions for tuberculosis and the tuberculosis prevention and treatment service system, and to provide reasonable support for further strengthening the capacity of designated medical institutions for tuberculosis. Methods: This study was initiated and carried out by Beijing Chest Hospital affiliated to Capital Medical University/Clinical Center for Tuberculosis Prevention and Control of China CDC (hereinafter referred to as "Clinical Center") by means of questionnaire survey, and the investigation was carried out from March to November 2023. During this period, the clinical center distributed questionnaires to the hospital member units of "Beijing Tuberculosis Diagnosis and Treatment Technology Innovation Alliance", retrospectively collected their tuberculosis-related diagnosis and treatment data from 2017 to 2022, and used descriptive statistical methods to analyze the number of tuberculosis beds, outpatients and hospitalizations in medical institutions. The results were expressed in absolute numbers (percentages), and three-line tables, bar charts and line charts were drawn to describe the analysis results and changing trends. Results: The 54 medical institutions surveyed in this survey included 21 provincial-level designated medical institutions and 33 prefecture-level designated medical institutions. Most medical institutions have set up clinical departments, auxiliary departments and functional departments to undertake public health tasks of infectious diseases. The tuberculosis laboratory in the hospital has a comprehensive ability and has the detection technology needed for most tuberculosis diagnosis; The number of tuberculosis beds, children's tuberculosis beds and ICU beds all showed an increasing trend from 2017 to 2022. The proportion of tuberculosis beds in the hospital decreased slightly, from 39.31% in 2017 to 34.76% in 2022, showing a slight downward trend. Compared with the hospital surveyed, the number of tuberculosis outpatients in 2019 was 562 029, and the number of outpatients in 2020-2022 was 462 328, 519 630 and 424 069 respectively, which was significantly lower than that in 2019. The number of tuberculosis outpatients in medical institutions decreased significantly from 2020 to 2022. By analyzing the proportion of patients with different types of tuberculosis, the proportion of sensitive tuberculosis outpatients in 2017-2022 decreased from 84.49% in 2017 to 78.05% in 2022, showing a downward trend year by year. The proportion of patients with multidrug-resistant/ rifampin-resistant tuberculosis increased from 2.03% in 2017 to 7.18% in 2022. From 2017 to 2019, the total number of inpatients with tuberculosis showed an upward trend. Compared with 2019, the number of inpatients in 2020, 2021 and 2022 showed a downward trend, and the decline in 2020 was large (down 14.94% compared with 2019). Among the inpatients, the absolute number and proportion of patients with sensitive pulmonary tuberculosis remained relatively stable, and the number and proportion of inpatients with multidrug-resistant/rifampin-resistant pulmonary tuberculosis increased year by year. Conclusions: Most medical institutions have the capacity to carry out routine diagnosis and treatment of tuberculosis, but the public health function needs to be strengthened. The transformation of medical institutions requires proper guidance and adequate support. During 2019-2022, most medical institutions were affected by the COVID-19 epidemic, and their tuberculosis diagnosis and treatment work also changed to varying degrees. During this period, hospitals took various measures to overcome difficulties and tried their best to maintain the normal development of tuberculosis diagnosis and treatment, and the tuberculosis diagnosis and treatment work of various institutions gradually resumed in 2022.

[Quantitative comparison of binocular suppression of patients with anisometropic amblyopia and ametropic amblyopia].

Objective: To explore the differences in clinical characteristics and interocular interactions between patients with anisometropic amblyopia and ametropic amblyopia. Methods: Cross-sectional study. The newly diagnosed anisometropic (the binocular difference in spherical equivalent≥1.00 D) amblyopia patients and ametropic amblyopia patients (aged 4 to 6 years) in Beijing Tongren Hospital from January 2020 to December 2022 were involved. Patients were further categorized by the refractive status after cycloplegia, including hyperopia, myopia, astigmatism, hyperopia with astigmatism, myopia with astigmatism, mild anisometropia and severe anisometropia. Quantitative measurements of best-corrected visual acuity (logMAR), stereoacuity (transformed to log units), perceptual eye position and interocular suppression were performed, and the differences between groups were analyzed. The rank sum test was used for statistical evaluation. Results: The average age of 45 ametropic amblyopia patients (21 males and 24 females) and 84 anisometropic amblyopia patients (48 males and 36 females) was 5.0 (4.0, 5.0) years and 5.0 (4.0, 6.0) years, respectively. The interocular differences in spherical equivalent [2.56 (1.50, 4.19) D vs. 0.25 (0.13, 0.56) D] and best-corrected visual acuity [0.40 (0.18, 0.70) logMAR vs. 0.07 (0.00, 0.12) logMAR] were larger in patients with anisometropic amblyopia than those with ametropic amblyopia. The anisometropic amblyopia patients had worse stereoacuity [2.60 (2.00, 2.90) log arcsec vs. 2.00 (2.00, 2.30) log arcsec] and deeper suppression [20.0% (13.3%, 40.0%) vs. 10.0% (0, 23.3%)], compared with the ametropic amblyopia patients. The differences were all statistically significant (P<0.05). The suppression and stereoacuity between patients with hyperopic anisometropic amblyopia [suppression, 30.0% (17.5%, 50.0%); stereoacuity, 2.90 (2.30, 2.90) log arcsec] and astigmatic anisometropic amblyopia [suppression, 10.0% (0, 20.0%); stereoacuity, 2.00 (2.00, 2.30) log arcsec] were significantly different (P<0.05). The differences of suppression and stereoacuity between patients with severe (binocular difference in spherical equivalent>2.50 D) [suppression, 30.0% (20.0%, 53.3%); stereoacuity, 2.90 (2.57, 2.90) log arcsec] and mild anisometropia [suppression, 20.0% (0, 30.0%); stereoacuity, 2.00 (2.00, 2.90) log arcsec] were also statistically significant (P<0.05). Conclusions: Patients with anisometropic amblyopia have deeper binocular suppression, worse stereoacuity and more severe binocular interaction abnormality than those with ametropic amblyopia. The severity of anisometropia affects the degree of the interaction abnormality.

Endurance Training Inhibits the JAK2/STAT3 Pathway to Alleviate Sarcopenia.

Aging leads to a decrease in muscle function, mass, and strength in skeletal muscle of animals and humans. The transcriptome identified activation of the JAK/STAT pathway, a pathway that is associated with skeletal muscle atrophy, and endurance training has a significant effect on improving sarcopenia; however, the exact mechanism still requires further study. We investigated the effect of endurance training on sarcopenia. Six-month-old male SAMR1 mice were used as a young control group (group C), and the same month-old male SAMP8 mice were divided into an exercise group (group E) and a model group (group M). A 3-month running exercise intervention was performed on group E, and the other two groups were kept normally. Aging caused significant signs of sarcopenia in the SAMP8 mice, and endurance training effectively improved muscle function, muscle mass, and muscle strength in the SAMP8 mice. The expression of JAK2/STAT3 pathway factor was decreased in group E compared with group M, and the expression of SOCS3, the target gene of STAT3, and NR1D1, an atrophy-related factor, was significantly increased. Endurance training significantly improved the phenotypes associated with sarcopenia, and the JAK2/STAT3 pathway is a possible mechanism for the improvement of sarcopenia by endurance training, while NR1D1 may be its potential target. Keywords: Sarcopenia, Endurance training, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), Nuclear receptor subfamily 1, group D member 1 (Nr1d1).

Longitudinal characterization of serum metabolome and lipidome reveals that the ceramide profile is associated with metabolic health in early postpartum cows experiencing different lipolysis.

Reduced feed intake in early lactation prompts increased fat mobilization to meet dairy cows' energy needs for milk production. The increased lipolysis in cows presents significant health risks with unclear mechanisms. The objectives of our study were to compare the longitudinal profiles of metabolites and lipids of serum from high and low-lipolysis cows. Forty multiparous Holstein dairy cows were enrolled in the retrospective study. Serum samples were collected on d 7 before expected calving, as well as on d 5, d 7, d 14, and d 21 postpartum. Dairy cows were grouped according to mean serum nonesterified fatty acids on d 5 and 7 after parturition as low (<0.600 mmol/L; n = 8; LFM) and high (>0.750 mmol/L; n = 8; HFM), indicating fat mobilization during early lactation. Lactational performance and serum metabolic parameters related to glucose and lipid metabolism, liver functions, oxidative status, and inflammatory responses were determined. Serum samples were subjected to LC-MS-based metabolomics and lipidomics. Despite differences in postpartum BW change, there were no observed variations in milk yield and composition between 2 groups. Serum BHBA, glucose, leptin, aspartate aminotransferase, IL-6, and TNF-α were greater in cows with HFM than in LFM. Serum adiponectin, revised quantitative insulin sensitivity check index and albumin were lower in cows with HFM than LFM. Intensified fat mobilization in the HFM cows came along with reduced estimated insulin sensitivity, impaired liver functions, and increased oxidative stress and inflammatory responses. Differences in metabolic patterns were observed across the transition period when comparing serum blood matrices (e.g., in different amino acids, acylcarnitines, and sphingolipids). The serum metabolome of the HFM cows was characterized by higher concentrations of glycine, acylcarnitines, carnosine, Cer(d20:0/18:0), Cer(d18:1/16:0), and Cer(t18:0/24:0) compared with LFM. The differential serum metabolites and lipids at different sampling times during the peripartum period were enriched in the sphingolipid metabolism. Differences in serum metabolic status parameters suggest that cows adopt varied metabolic adaptation strategies to cope with energy deficits postpartum. Our investigation found a comprehensive remodeling of the serum metabolic profiles in transition dairy cattle, highlighting the significance of alterations in sphingolipid species, as they play a crucial role in insulin resistance and metabolic disorders.