Impact of polygenic risk score for triglyceride trajectory and diabetic complications in subjects with type 2 diabetes based on large electronic medical record data from Taiwan: a case control study.

BACKGROUND: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. METHODS: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. RESULTS: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). CONCLUSIONS: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

Standardization method, testing scenario, and accuracy of the infrared prediction model affect the standardization accuracy of milk mid-infrared spectra.

The widespread use of milk mid-infrared (MIR) spectroscopy for phenotype prediction has urged the application of prediction models across regions and countries. Spectra standardization is the most effective way to reduce the variability in the spectral signal provided by different instruments and labs. This study aimed to develop different standardization models for MIR spectra collected by multiple instruments, across 2 provinces of China, and investigate whether the standardization method (piecewise direct standardization, PDS, and direct standardization, DS), testing scenario (standardization of spectra collected on the same day or after 7 mo), infrared prediction model accuracy (high or low), and instrument (6 instruments from 2 brands) affect the performance of the standardization model. The results showed that the determination coefficient (R2) between absorbance values at each wavenumber provided by the primary and the secondary instruments increased from less than 0.90 to nearly 1.00 after standardization. Both PDS and DS successfully reduced spectra variation among instruments, and performed significantly better than non-standardization (P < 0.05). However, DS was more prone to overfitting than PDS. Standardization accuracy was higher when tested using spectra collected on the same time compared with those collected 7 mo after (P < 0.05), but great improvement in model transferability was obtained for both scenarios compared with the non-standardized spectra. The less accurate infrared prediction model (for C8:0 and C10:0 content) benefited the most (P < 0.05) from spectra standardization compared with the more accurate model (for total fat and protein content). For spectra collected after 7 mo from standardization, after PDS the RMSE between predictions obtained by different machines decreased on average by 86 and 94% compared with the values before standardization, for C8:0 and C10:0 respectively. The secondary instrument had no significant effect on the R2 between predictions (P > 0.05). The variation in the spectral signal provided by different instruments was successfully reduced by standardization across 2 provinces in China. This study lays the foundations for developing a national MIR spectra database to provide consistent predictions across provinces to be used in dairy farm management and breeding programs in China. Besides, this provides opportunities for data exchange and cooperation at international levels.

[Detection of PIK3CA gene mutation and its related prognosis in colorectal cancer based on next-generation sequencing].

Objectives: To investigate the mutation of PIK3CA in colorectal cancer and to analyze their clinicopathological features, and evaluate their role in clinical treatment and prognostication. Methods: A total of 128 paraffin-embbeded tissue samples of colorectal cancer from Shanxi Cancer Hospital from 2018 to 2021 were collected. DNA was extracted from the samples, and next-generation sequencing (NGS) was used to detect PIK3CA mutation. The relationship between PIK3CA mutation, their clinicopathological features, and prognosis were analyzed. Results: Among the 128 colorectal cancer samples, there were 75 males and 53 females; with aged range 32-86 years, median 61.5 years, 27 (21.09%) had PIK3CA mutations. Colorectal cancer with PIK3CA mutation was more likely to occur in male patients (P=0.007), which was related to tumor site (P=0.032), tumor size (P=0.029) and TP53 wild-type (P=0.001). The common site mutations of PIK3CA mostly occurred in tumors with tumor mutation burden≥10 Muts/Mb (P=0.031).PIK3CA mutation had no significant effect on the survival prognosis of patients, but the efficacy of anti-angiogenic therapy was poor in these patients. Conclusions: PIK3CA mutation is a common mutation in colorectal cancer and plays an important role in the occurrence and development of colorectal cancer. PIK3CA mutation may lead to resistance to anti-angiogenic drugs in colorectal cancer, but its impact on survival and prognosis to patients needs further study.

[Correlation of MYB/NFIB gene fusion with the grade and prognosis of head and neck adenoid cystic carcinoma and the concordance of two detection methods].

Objective: To explore the correlation between MYB/NFIB gene fusion and clinicopathological features such as tumor grade and prognosis of head and neck adenoid cystic carcinoma (ACC), and to assess the concordant rate of fluorescent in situ hybridization (FISH) with MYB and NFIB immunohistochemistry. Methods: FISH detection of MYB/NFIB gene fusion was performed on 48 head and neck ACC cases and 15 non-ACC salivary gland tumors at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China during April 2014 and January 2020. ACC cases were divided into grade Ⅰ-Ⅱ, grade Ⅲ and high-grade transformation, according to pathological grading criteria. Prognosis, FISH results and other clinicopathological characteristics were analyzed. MYB and NFIB immunohistochemistry was performed on the 48 ACC and 15 non-ACC cases. The diagnostic accuracy of FISH and immunohistochemistry was compared. Results: FISH detected MYB/NFIB gene fusion in 41.7% (20/48) of the ACC. Its positive rate was inversely correlated with higher pathological grades (P=0.036). The higher histological grade was linked to worse progression-free survival (P=0.024), whereas there was no correlation between the status of gene fusion detected by FISH and progression-free survival (P=0.536). FISH didnot detect MYB/NFIB gene fusion in 15 non-ACC salivary gland tumors The specificity of diagnosing ACC is 100% for both FISH detection of gene fusion and immunohistochemical detection of MYB expression. However, the sensitivity for both methods was only about 41.7%, respectively. By combining FISH and MYB immunohistochemistry, the sensitivity for diagnosing ACC was increased to 66.7%. Conclusions: MYB/NFIB gene fusion has a lower detection rate in grade Ⅲ ACC and high-grade transformation ACC. Meanwhile gene fusion status is not correlated with prognosis. The sensitivity for diagnosing ACC can be improved by combining FISH and MYB immunohistochemistry.

[Analysis of compliance with lung protective mechanical ventilation strategy in patients with acute respiratory distress syndrome].

Objective: To assess the compliance with a lung protective ventilation strategy and to evaluate the relationship with prognosis in patients with acute respiratory distress syndrome (ARDS). Methods: In the prospective multicenter cohort study (CHARDS), patients with ARDS undergoing invasive mechanical ventilation were enrolled to collect essential information, mechanical ventilation data, and prognostic data. Compliance was operationally defined as tidal volume ≤7 ml/kg predicted body weight (PBW) or plateau pressure ≤30 cmH2O or driving pressure≤15 cmH2O. Tidal volume data collected 7 days prior to ventilation after ARDS diagnosis were categorized into four groups: standard group (Group A, 100% compliance), non-standard group (Group B, 50%-99% compliance, Group C,1%-49% compliance,and Group D,totally non-compliant). Plateau pressure and drive pressure measurements were recorded on the first day. Stepwise regression, specifically Logistics regression, was used to identify the factors influencing ICU survival. Results: A total of 449 ARDS patients with invasive mechanical ventilation were included; the proportion of mild, moderate, and severe patients was 71 (15.8%), 198 (44.1%) and 180 (40.1%), respectively. During the first 7 days, a total of 2880 tidal volume measurements were recorded with an average tidal volume of (6.89±1.93) ml/kg PBW. Of these measurements, 53.2% were found to be≤7 ml/kg PBW. The rates of compliance with lung protective mechanical ventilation were 29.8% (134/449), 24.5% (110/449), 23.6% (106/449), and 22% (99/449) in groups A, B, C, and D, respectively. In the standard group, the tidal volume for mild ARDS patients was 18.3%(13/71), while it was 81.7%(58/71)in the non-standard group. Similarly, in patients with moderate ARDS, the tidal volume was 25.8% (51/198) in the standard group, while it was 74.2% (147/198) in the non-standard group. Finally, in patients with severe ARDS, the tidal volume was 38.9% (70/180) in the standard group, while it was 61.1% (110/180) in the non-standard group. Notably, the compliance rate was higher in patients with moderate and severe ARDS in group A compared to patients with mild and moderate ARDS (18.3% vs. 25.8% vs. 38.9%, χ2=13.124, P=0.001). Plateau pressure was recorded in 221 patients, 95.9% (212/221) patients with plateau pressure≤30 cmH2O, and driving pressure was recorded in 207 patients, 77.8% (161/207) patients with a driving pressure ≤15 cmH2O.During the first 7 days, the mortality rate in the intensive care unit (ICU) was lower in the tidal volume standard group compared to the non-standard group (34.6% vs. 51.3%, χ2=10.464, P=0.001). In addition, the in-hospital mortality rate was lower in the standard group compared to the non-standard group (39.8% vs. 57%, χ2=11.016, P=0.001).The results of the subgroup analysis showed that the mortality rates of moderate and severe ARDS patients in the standard group were significantly lower than those in the non-standard group, both in the ICU and in the hospital (all P<0.05). However, there was no statistically significant difference in mortality among mild ARDS patients (all P>0.05). Conclusions: There was high compliance with recommended lung protective mechanical ventilation strategies in ARDS patients, with slightly lower compliance in patients with mild ARDS, and high compliance rates for plateau and drive pressures. The tidal volume full compliance group had a lower mortality than the non-compliance group, and showed a similar trend in the moderate-to-severe ARDS subgroup, but there was no significant correlation between compliance and prognosis in patients with mild ARDS subgroup.

[Clinical characteristics and surgical outcomes of pediatric epiretinal membranes without specific etiologies].

Objective: To describe clinical characteristics and surgical outcomes of pediatric epiretinal membranes (ERMs) without specific etiologies. Methods: Medical data of a cohort of pediatric patients (≤14 years) who had ERMs without specific etiologies, underwent surgical removal from January 2019 to September 2021, and were followed up for at least 12 months were retrospectively reviewed. Age at presentation, chief complaints, color fundus photographs, optical coherence tomographic images, preoperative and postoperative visual acuities, anatomical changes, and postoperative complications were assessed. Results: There were 14 patients (17 eyes), including 5 females (6 eyes) and 9 males (11 eyes). The mean age at surgery was 6.31±2.91 years, and the follow-up duration was 17.3±9.5 months. Eight patients were found to have low vision in the school physical examination. Fifteen eyes had an appearance of cellophane macular reflex on fundus images. On optical coherence tomographic images, 10 eyes had"taco"folds, and 7 eyes had"ripple"folds. Five eyes had ellipsoid zone disruptions, while 12 eyes had ellipsoid zone integrity. The preoperative and postoperative best-corrected visual acuities in logMAR were 0.532±0.302 and 0.340±0.298. One patient suffered traumatic cataract and secondary retinal detachment postoperatively, and after further vitrectomy, the retina became attached. Conclusion: Pediatric ERMs without specific etiologies were mostly found in school-age children with cellophane macular reflex and"taco"folds. Vitrectomy may result in both potential visual acuity and macular anatomical improvements.

Association between sarcopenia and prediabetes among non-elderly US adults.

AIM: To explore the specific association between sarcopenia and prediabetes based on large population samples. METHODS: A total of 16,116 U.S. adults aged 20-59 with dual energy X-ray absorptiometry (DXA) was identified from the National Health and Nutrition Examination Surveys (NHANES). Sarcopenia was defined according to appendicular skeletal muscle mass (ASM) adjusted for body mass index (BMI). Multivariable binary logistic regression models were used to ascertain odds ratios (ORs) for developing prediabetes. Stratified analyses were also performed. RESULTS: Prevalence of prediabetes was higher in the sarcopenia group (n = 1055) compared with the non-sarcopenia group (n = 15,061) (45.50% vs 28.74%, P < 0.001). Sarcopenia was strongly associated with an increased risk of prediabetes after full adjustment (OR = 1.21, 95CI%: 1.05, 1.39, P = 0.009). In the stratified analysis, this association remained significant independent of obesity, triglycerides, and low-density lipoprotein cholesterol levels. When sarcopenia subjects combined with obesity especially central obesity, the risk of prediabetes was the highest (OR = 2.63, 95CI%: 2.22, 3.11, P < 0.001). Furthermore, a greater proportion of any of impaired glucose tolerance (IGT) individuals was observed in the sarcopenia group compared to the non-sarcopenia group among prediabetes population (41.72% vs 24.06%, P < 0.001). CONCLUSIONS: Sarcopenia was positively associated with prevalent prediabetes especially IGT in the non-elderly. Moreover, synergistic interactions between the sarcopenia and obesity could greatly increase the risk of prediabetes.

Phenylacetylglutamine as a novel biomarker of type 2 diabetes with distal symmetric polyneuropathy by metabolomics.

PURPOSE: Type 2 diabetes mellitus (T2DM) with distal symmetric polyneuropathy (DSPN) is a disease involving the nervous system caused by metabolic disorder, while the metabolic spectrum and key metabolites remain poorly defined. METHODS: Plasma samples of 30 healthy controls, 30 T2DM patients, and 60 DSPN patients were subjected to nontargeted metabolomics. Potential biomarkers of DSPN were screened based on univariate and multivariate statistical analyses, ROC curve analysis, and logistic regression. Finally, another 22 patients with T2DM who developed DSPN after follow-up were selected for validation of the new biomarker based on target metabolomics. RESULTS: Compared with the control group and the T2DM group, 6 metabolites showed differences in the DSPN group (P < 0.05; FDR < 0.1; VIP > 1) and a rising step trend was observed. Among them, phenylacetylglutamine (PAG) and sorbitol displayed an excellent discriminatory ability and associated with disease severity. The verification results demonstrated that when T2DM progressed to DSPN, the phenylacetylglutamine content increased significantly (P = 0.004). CONCLUSION: The discovered and verified endogenous metabolite PAG may be a novel potential biomarker of DSPN and involved in the disease pathogenesis.

Aquaporins in Diabetes Insipidus.

Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understanding the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI). This is followed by a discussion of regulatory mechanisms underlying CDI and NDI, with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R) and the water channel molecule, aquaporin 2 (AQP2). The clinical manifestation, diagnosis, and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.

A Missing Origin of the Tau Protein Aggregation Pathway Triggered by Thermal and Biological Forces.

Fluctuations in mechanical force vectors within living cells can substantially influence the behavior and functions of proteins. Tau protein can spontaneously be raptured and entangled in refolding under picoNewton compressive forces that are biologically available in a living cell: a hidden aggregation pathway due to stress and crowding. Our findings were achieved through a customized modification of atomic force microscopy (AFM) for single-molecule manipulation. This previously hidden phenomenon of proteins rupturing collectively while subsequently and spontaneously refolding into a complex entangled conformation, distinct from the Tau protein's folded or unfolded states, could potentially explain the early-event initiation of the aggregation of the Tau protein seen in various neurodegenerative diseases. This article introduces our recent discovery of the missing Tau protein property that is of significant relevance to the Tau protein and neurodegenerative disease research and medical treatment, aiming to stimulate the collective observation and a new perspective on the Tau aggregation mechanism and disease mechanism studies.

METTL21C mediates lysine trimethylation of IGF2BP1 to regulate chicken myoblast proliferation.

1. Methyltransferase-like 21C (METTL21C) and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) play important roles in the proliferation of chicken myoblasts. However, it remains unclear whether there is protein-protein interaction between METTL21C and IGF2BP1 to regulate proliferation of chicken myoblasts.2. In this study, the Igf2bp1 gene was amplified from cDNA of liver tissue of Lueyang black-bone chicken to construct the overexpression vector HA-Igf2bp1. The HA-Igf2bp1 and Flag-Mettl21c vectors were individually transfected and co-transfected into HEK293T, respectively. Co-immunoprecipitation (Co-IP) assay indicated a protein-protein interaction between METTL21C and IGF2BP1.3. Using the Western blotting and LC-MS/MS, it was found that METTL21C could mediate the lysine methylation modification of IGF2BP1. Furthermore, the His-tagged overexpression vector HA-Igf2bp1-His was constructed, transfected and co-transfected with Flag-Mettl21c into HEK293T. His-tagged IGF2BP1 was purified by nickel ion affinity chromatography. Western blotting revealed that IGF2BP1 was successfully purified, and the trimethylation modification level of co-transfection group was significantly elevated compared with the single-transfection Igf2bp1 group.4. Mettl21c and Igf2bp1 overexpression vectors were transfected and co-transfected into primary chicken myoblasts, respectively. The results of 5-ethynyl-2'-deoxyuridine assay and the expression level of Pax7 and MyoD indicated that overexpression of Igf2bp1 alone inhibited the chicken myoblast proliferation, whereas co-expression of Mettl21c and Igf2bp1 eliminated the inhibitory effects of Igf2bp1, thereby favouring cell proliferation and differentiation.5. The results, for the first time, revealed that METTL21C mediated the lysine trimethylation modification of IGF2BP1 to regulate the proliferation of chicken myoblasts, which provided a new insight into in-depth analysis of the molecular mechanism of METTL21C methylation involved in regulating the growth and development of skeletal muscle in Lueyang black-bone chicken.

[Clinical factors affecting the prognosis of lower gingival squamous cell carcinoma].

OBJECTIVE: To define the clinical factors that influence local recurrence and survival in patients with lower gingival squamous cell carcinoma (LGSCC) and determine whether bone invasion is an independent prognostic factor for them. METHODS: A total of 104 patients with LGSCC hospitalized in Peking University Stomatology Hospital from June 2013 to December 2015 were enrolled in this retrospective study.All the patients were followed-up for more than 3 years.The degree of bone invasion was assessed using preoperative imaging data (CT and panoramic radiograph).The degree of bone invasion was divi-ded into four categories: no bone invasion, invasion of cortical bone, invasion of bone marrow cavity, and invasion of the mandibular canal.According to the central position of tumor, it was divided into two types: anterior mandibular invasion (anterior region of the mental foramen) and posterior mandibular invasion (posterior region of the mental foramen). RESULTS: of different invasion depth groups were compared using Mann-Whitney U test.P value < 0.05 was considered to be statistically significant.Kaplan-Meier survival analysis method was used to draw survival curve, and COX regression was used to explore the risk ratio (HR) and 95% confidence interval (CI) of prognostic factors of LGSCC. RESULTS: The follow-up results showed that the 1-, 3-, and 5-year survival rates of LGSCC in this group were 91%, 84%, 82%, respectively.32.7%(34/104) of patients had cervical lymph node metastasis.The cervical lymph node metastasis rate of the anterior segment of the mandible was 12.5%(2/16), and 36.4%(32/88) for the posterior segment of the mandible (P < 0.05).Univariate and multivariate COX analysis showed that the N stage and local recurrence were the prognostic factors of LGSCC patients (P < 0.05). CONCLUSION: As the degree of mandibular invasion increases, the prognosis of patients with mandibular gum cancer becomes worse.N stage and local recurrence are prognostic risk factors for LGSCC.The incidence of cervical lymph node metastasis for LGSCC is related to the primary tumor location.It is concluded that tumors located at the posterior of the mandible might be more prone to cervical lymph node metastasis than the anterior of the mandible.Thus various levels of cervical lymph node dissection strategies should be adopted for different sites of LGSCC.

Meta-analysis of InterTan, PFNA and PFNA-II internal fixation for the treatment of unstable intertrochanteric fractures in elderly individuals.

Elderly individuals are often affected by osteoporosis and have poor stability after fracture reduction. Moreover, there is still controversy regarding the clinical effects of the treatment for unstable intertrochanteric fractures in the elderly. The Cochrane, Embase, PubMed, and other databases were searched, and a meta-analysis of the literature on the treatment of unstable intertrochanteric fractures of the elderly with InterTan, PFNA, and PFNA-II was conducted. Seven studies were screened, with a total of 1236 patients. Our meta-analysis results show that InterTan is not significantly different from PFNA in terms of operation and fluoroscopy times, but it takes longer than PFNA-II. In terms of postoperative screw cut, pain, femoral shaft fracture, and secondary operations, InterTan is superior to PFNA and PFNA-II. Conversely, in terms of intraoperative blood loss, hospital stay, and postoperative Harris score, there is no significant difference between InterTan and PFNA and PFNA-II. Compared to PFNA and PFNA-II, InterTan internal fixation has advantages in the treatment of unstable intertrochanteric fractures in elderly individuals in terms of screw cutting, femoral shaft fractures, and secondary operations. However, InterTan operation and fluoroscopy times take longer than PFNA and PFNA-II.

[Clinical analysis of 66 cases of pseudo fever].

Some patients who present with a "fever" may only have a localized increase in body surface temperature, while their core body temperature remains normal. This phenomenon is commonly referred to as pseudo fever. A retrospective analysis of clinical data from January 2013 to January 2020 at our fever clinic showed that 66 adolescents were diagnosed with pseudo fever. These patients typically showed a gradual increase in axillary temperature after their cold symptoms had disappeared. Most patients reported no significant complaints other than mild dizziness. Laboratory tests showed no significant abnormalities, and antipyretics were ineffective in lowering their body temperature. Pseudo fever is a relatively independent clinical phenomenon that is distinct from functional fever or simulated fever, and its underlying mechanism remains to be studied.

[Change trends and related risk factors of disease burden on mesothelioma in Jiangsu Province from 1990 to 2019].

Objective: To analyze the change trends and risk factors of mesothelioma disease burden in Jiangsu Province from 1990 to 2019. Methods: In January 2022, using the 2019 Global Burden of Disease Study Data, the Joinpoint regression model was used to analyze the change trends of incidence, mortality, disable-adjusted life years (DALY) and premature mortality of mesothelioma residents in Jiangsu Province from 1990 to 2019, and the attribution level of mesothelioma risk factors was estimated by population attributing fraction. Results: The standardized incidence rates of mesothelioma in Jiangsu Province from 1990 to 2019 ranged from 0.07/10(5) to 0.09/10(5), with an average annual percentage change (AAPC) of -1.1% (t=-13.56, P<0.001). AAPCs in males and females were -0.3% (t=-2.18, P=0.029) and -1.6% (t=-11.39, P<0.001), respectively. The standardized mortality rates of mesothelioma ranged from 0.07/10(5) to 0.09/10(5), the AAPC was -1.1% (t=-12.23, P<0.001), AAPC was -1.6% (t=-14.09, P<0.001) for females, and there was no significant change in males (t=-1.83, P=0.068). The premature mortality was 0.004%-0.006%, the AAPC was -1.0% (t=-4.40, P<0.001), AAPC was -1.7% (t=-13.72, P<0.001) for females, and there was no significant change in males (t=-0.68, P=0.495). The standardized DALY rates ranged from 1.86/10(5) to 2.32/10(5), the AAPC was -0.9% (t=-11.08, P<0.001), AAPC was -1.6% (t=-11.05, P<0.001) for females, and there was no significant change in males (t=-0.95, P=0.343). Both the standardized years of life lost (YLL) rate and the standardized years lived with disability (YLD) rate showed a decreasing trend, and the AAPCs were -0.9% (t=-7.66, P<0.001) and -1.0% (t=-12.88, P<0.001), respectively. The proportion of YLL in DALY was more than 98.5%. Among the risk factors for mesothelioma burden attribution, the AAPC attributed to occupational asbestos exposure of DALY was 1.4% (t=3.43, P=0.001). The AAPC of DALY rate of standardized attribution was -1.7% (t=-12.11, P<0.001) . Conclusion: The overall burden of mesothelioma in Jiangsu Province is decreasing, occupational asbestos exposure is still the main risk factor of mesothelioma in Jiangsu Province, and early diagnosis and treatment should be strengthened.

Global, regional prevalence, and risk factors of osteoporosis according to the World Health Organization diagnostic criteria: a systematic review and meta-analysis.

This systematic review and meta-analysis estimated the global, regional prevalence, and risk factors of osteoporosis. Prevalence varied greatly according to countries (from 4.1% in Netherlands to 52.0% in Turkey) and continents (from 8.0% in Oceania to 26.9% in Africa). Osteoporosis is a common metabolic bone disorder in the elderly, usually resulting in bone pain and an increased risk of fragility fracture, but few summarized studies have guided global strategies for the disease. Therefore, we pooled the epidemiologic data to estimate the global, regional prevalence, and potential risk factors of osteoporosis. We conducted a comprehensive literature search through PubMed, EMBASE, Web of Science, and Scopus, to identify population-based studies that reported the prevalence of osteoporosis based on the World Health Organization (WHO) criteria. Meta-regression and subgroup analyses were used to explore the sources of heterogeneity. The study was registered in the PROSPERO database (CRD42021285555). Of the 57,933 citations evaluated, 108 individual studies containing 343,704 subjects were included. The global prevalence of osteoporosis and osteopenia was 19.7% (95%CI, 18.0%-21.4%) and 40.4% (95%CI, 36.9%-43.8%). Prevalence varied greatly according to countries (from 4.1% in Netherlands to 52.0% in Turkey) and continents (from Oceania 8.0% to 26.9% in Africa). The prevalence was higher in developing countries (22.1%, 95%CI, 20.1%-24.1%) than in developed countries (14.5%, 95%CI, 11.5%-17.7%). Our study indicates a considerable prevalence of osteoporosis among the general population based on WHO criteria, and the prevalence varies substantially between countries and regions. Future studies with robust evidence are required to explore risk factors to provide effective preventive strategies for the disease.

Probing functional conformation-state fluctuation dynamics in recognition binding between calmodulin and target peptide.

Conformational dynamics play a crucial role in protein functions. A molecular-level understanding of the conformational transition dynamics of proteins is fundamental for studying protein functions. Here, we report a study of real-time conformational dynamic interaction between calcium-activated calmodulin (CaM) and C28W peptide using single-molecule fluorescence resonance energy transfer (FRET) spectroscopy and imaging. Plasma membrane Ca-ATPase protein interacts with CaM by its peptide segment that contains 28 amino acids (C28W). The interaction between CaM and the Ca-ATPase is essential for cell signaling. However, details about its dynamic interaction are still not clear. In our current study, we used Cyanine3 labeled CaM (N-domain) and Dylight 649 labeled C28W peptide (N-domain) to study the conformational dynamics during their interaction. In this study, the FRET can be measured when the CaM-C28W complex is formed and only be observed when such a complex is formed. By using single-molecule FRET efficiency trajectory and unique statistical approaches, we were able to observe multiple binding steps with detailed dynamic features of loosely bound and tightly bound state fluctuations. The C-domain of CaM tends to bind with C28W first with a higher affinity, followed by the binding of the CaM N-domain. Due to the comparatively high flexibility and low affinity of the N-domain and the presence of multiple anchor hydrophobic residues on the peptide, the N-domain binding may switch between selective and non-selective binding states, while the C-domain remains strongly bound with C28W. The results provide a mechanistic understanding of the CaM signaling interaction and activation of the Ca-ATPase through multiple-state binding to the C28W. The new single-molecule spectroscopic analyses demonstrated in this work can be applied for broad studies of protein functional conformation fluctuation and protein-protein interaction dynamics.

[The mediating role of anxiety and depression for family members of ICU patients in perceived social support and fatigue].

To analyze the mediating role of anxiety and depression in perceived social support and fatigue in ICU patients' families, and to provide a theoretical evidence for alleviating their fatigue status. A total of 223 family members of ICU patients who received treatment at the Affiliated Hospital of Jiangnan University from October 2020 to April 2021 were selected as the study subjects. The general data questionnaire, perceived social support scale (PSSS), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9) and fatigue assessment instrument (FAI) were used to conduct a survey. Among 223 family members of ICU patients, 155(69.51%) had fatigue problems. There were statistically significant differences in total fatigue scores of ICU patients' family members in terms of gender, age, education level, relationship with patients, residence, payment method and per capita monthly income (P<0.05). Anxiety, depression and fatigue were negatively correlated with perceived social support (r are -0.353, -0.276 and -0.416, respectively, all P<0.01). Depression and fatigue were positively correlated with anxiety (r are 0.808 and 0.703, respectively, all P<0.01), and fatigue was also positively correlated with depression (r= 0.665, P<0.01). Anxiety and depression had a partial mediating effect on perceived social support and fatigue, and the total indirect effect size was 52.64%. Comprehensive intervention on the level of social support, anxiety and depression is helpful to improve the fatigue status of ICU patients' family members.

[Application of cortical bone trajectory screw and sacral alar screw internal fixation for surgical treatment of lumbar adjacent segment degeneration].

Objective: To explore the application of cortical bone trajectory screw (CBTS) and sacral alar screw (SAS) internal fixation in the treatment of lumbar adjacent segment degeneration (ASD) and evaluate its clinical effect. Methods: Data of 24 patients who were diagnosed with ASD and treated by CBTS or SAS in Beijing Chaoyang Hospital were retrospectively reviewed. There were 14 males and 10 females with a mean age of (67.9±8.2) years. The patients were followed-up for (2.6±0.4) years. Perioperative parameters including operation time, intraoperative blood loss and postoperative time on the ground were counted. All patients were followed-up for at least 2 years. Visual analogue scale (VAS) and the Oswestry disability index (ODI) were compared between pre-operation and at the last follow-up. The internal fixation-related complications, pseudarthrosis and adjacent re-degeneration were evaluated in the follow-up. Results: There were 14 proximal ASD patients, 8 distal ASD patients, 1 both ends ASD patient and 1 ASD patient in between the fusion surgeries. Bone mineral density (BMD) T score of the adjacent vertebrae was -1.98±0.91 on average. The ASD patients were re-operated with CBTS and SAS internal fixation technique. A small incision was made in the revision surgery and the original fixation was not completely cut open and removed. The mean operation time was (125±36) min, mean blood loss was (85±33) ml. The postoperative ambulation time was (3.1±1.9) days, and the hospitalization time was (9.0±2.6) days. Before the operation, the average VAS (back pain) score was 5.2±1.0, the average of VAS (leg pain) score was 6.8±1.9 and ODI was 56.6%±12.8%. VAS score was reduced to 1.4±0.6 (waist pain) and 0.9±0.4 (leg pain). ODI was improved to 13.8%±6.3%. All the difference between preoperative and the last follow-up was statically significant (all P<0.01). No internal fixation failure, pseudarthrosis and adjacent re-degeneration were observed in the final follow-up. Conclusion: The application of CBTS and SAS internal fixation techniques in the surgical treatment of lumbar ASD has the advantages of less trauma, faster postoperative recovery, reliable internal fixation, and fewer complications, especially in patients with low bone mineral density.

[Clinicopathological features of angioimmunoblastic T-cell lymphoma pattern â ].

Objective: To investigate the clinicopathological features of angioimmunoblastic T-cell lymphoma pattern Ⅰ (AITL Pattern Ⅰ). Methods: The clinicopathological data of 11 AITL Pattern Ⅰ cases that were diagnosed at the Beijing Friendship Hospital Affiliated to Capital Medical University (10 cases) and Beijing Lu Daopei Hospital (1 cases) from January 2019 to October 2021 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of the tumor cells were tested, and clinicopathological features of cases were analyzed. Results: Among the 11 AITL Pattern Ⅰ cases, the male to female ratio was 1.2∶1.0. The median age was 59 years (range 47-78 years). Seven cases had B symptoms, while eleven cases presented with systemic lymphadenopathy. According to Ann Arbor system staging, two cases were classified as stage Ⅰ-Ⅱ, and 9 cases as stage Ⅲ-Ⅳ. Hepatosplenomegaly was present in two cases (2/11), three cases (3/11) had skin rash and pruritus, and two cases (2/11) had pleural effusion. Previously, 6 cases (6/11) were diagnosed as reactive hyperplasia, 1 case (1/11) as EBV-associated lymphoproliferative disorder, and 4 cases (4/11) as hyperplasia of lymphoid tissue, which was unable to exclude lymphoma. Histologically, all the 11 cases showed hyperplastic follicles in the paracortical regions with well-formed germinal centers. The hyperplastic follicles showed ill-defined borders and attenuated mantle zones in 7 cases. Mantle zones completely disappeared in 4 cases. The follicles were surrounded by a thin layer of atypical lymphocytes with bright or faintly stained cytoplasm. In 2 cases, the clear cells were located between the germinal centers and the thin residual mantle cell layers, showing a circular growth pattern. The cells were medium in size, with irregular karyotype, coarse chromatin and indistinct nucleoli. Immunohistochemically, CD21 staining showed that the meshworks of follicular dendritic cells(FDC)were mainly confined to the follicles. There was a subtle expansion of the meshworks of FDC in 4 cases with ill-defined borders. The atypical cells surrounding the follicles expressed CD3 (11/11), CD4 (11/11), PD-1 (11/11), CXCL13 (6/11), ICOS (10/11) and CD10 (7/11). PD-1 staining showed a strong perifollicular pattern, and a small number of positive cells were scattered around the high endothelial veins in the interfollicular region. CXCL13, ICOS and CD10 showed similar distribution patterns. EBV-encoded small RNA probe (EBER) in situ hybridization showed that EBER positive B lymphocytes were scattered in the interfollicular region (5-20/HPF) in all cases. T cell receptor gene rearrangement was monoclonal in all cases. Conclusions: Diagnosing AITL Pattern Ⅰ may be challenging and requires comprehensive analysis of clinical manifestations, histological morphology, immunophenotype and gene rearrangement results.