Agomelatine promotes differentiation of oligodendrocyte precursor cells and preserves white matter integrity after cerebral ischemic stroke.

White matter injury contributes to neurological disorders after acute ischemic stroke (AIS). The repair of white matter injury is dependent on the re-myelination by oligodendrocytes. Both melatonin and serotonin antagonist have been proved to protect against post-stroke white matter injury. Agomelatine (AGM) is a multi-functional treatment which is both a melatonin receptor agonist and selective serotonin receptor antagonist. Whether AGM protects against white matter injury after stroke and the underlying mechanisms remain elusive. Here, using the transient middle cerebral artery occlusion (tMCAO) model, we evaluated the therapeutic effects of AGM in stroke mice. Sensorimotor and cognitive functions, white matter integrity, oligodendroglial regeneration and re-myelination in stroke hemisphere after AGM treatment were analyzed. We found that AGM efficiently preserved white matter integrity, reduced brain tissue loss, attenuated long-term sensorimotor and cognitive deficits in tMCAO models. AGM treatment promoted OPC differentiation and enhanced re-myelination both in vitro, ex vivo and in vivo, although OPC proliferation was unaffected. Mechanistically, AGM activated low density lipoprotein receptor related protein 1 (LRP1), peroxisome proliferator-activated receptor γ (PPARγ) signaling thus promoted OPC differentiation and re-myelination after stroke. Inhibition of PPARγ or knock-down of LRP1 in OPCs reversed the beneficial effects of AGM. Altogether, our data indicate that AGM represents a novel therapy against white matter injury after cerebral ischemia.

Enhancement of the function of mesenchymal stem cells by using a GMP-grade three-dimensional hypoxic large-scale production system.

Background: Efficiently increasing the production of clinical-grade mesenchymal stem cells (MSCs) is crucial for clinical applications. Challenges with the current planar culture methods include scalability issues, labour intensity, concerns related to cell senescence, and heterogeneous responses. This study aimed to establish a large-scale production system for MSC generation. In addition, a comparative analysis of the biological differences between MSCs cultured under various conditions was conducted. Methods and materials: We developed a GMP-grade three-dimensional hypoxic large-scale production (TDHLSP) system for MSCs using self-fabricated glass microcarriers and a multifunctional bioreactor. Different parameters, including cell viability, cell diameter, immunophenotype, morphology, karyotype, and tumourigenicity were assessed in MSCs cultured using different methods. Single-cell RNA sequencing (scRNA-seq) revealed pathways and genes associated with the enhanced functionality of MSCs cultured in three dimensions under hypoxic conditions (3D_Hypo MSCs). Moreover, CD142 knockdown in 3D_Hypo MSCs confirmed its in vitro functions. Results: Inoculating 2 × 108 MSCs into a 2.6 L bioreactor in the TDHLSP system resulted in a final scale of 4.6 × 109 3D_Hypo MSCs by day 10. The 3D_Hypo MSCs retained characteristics of the 2D MSCs, demonstrating their genomic stability and non-tumourigenicity. Interestingly, the subpopulations of 3D_Hypo MSCs exhibited a more uniform distribution and a closer relationship than those of 2D MSCs. The heterogeneity of MSCs was strongly correlated with 'cell cycle' and 'stroma/mesenchyme', with 3D_Hypo MSCs expressing higher levels of activated stroma genes. Compared to 2D MSCs, 3D_Hypo MSCs demonstrated enhanced capabilities in blood vessel formation, TGF-ß1 secretion, and inhibition of BV2 proliferation, with maintenance of Senescence-Associated ß-Galactosidase (SA-ß-gal) negativity. However, the enhanced functions of 3D_Hypo MSCs decreased upon the downregulation of CD142 expression. Conclusion: The TDHLSP system led to a high overall production of MSCs and promoted uniform distribution of MSC clusters. This cultivation method also enhanced key cellular properties, such as angiogenesis, immunosuppression, and anti-aging. These functionally improved and uniform MSC subpopulations provide a solid basis for the clinical application of stem cell therapies.

The haplotype-resolved genome of diploid Chrysanthemum indicum unveils new acacetin synthases genes and their evolutionary history.

Acacetin, a flavonoid compound, possesses a wide range of pharmacological effects, including antimicrobial, immune regulation, and anticancer effects. Some key steps in its biosynthetic pathway were largely unknown in flowering plants. Here, we present the first haplotype-resolved genome of Chrysanthemum indicum, whose dried flowers contain abundant flavonoids and have been utilized as traditional Chinese medicine. Various phylogenetic analyses revealed almost equal proportion of three tree topologies among three Chrysanthemum species (C. indicum, C. nankingense, and C. lavandulifolium), indicating that frequent gene flow among Chrysanthemum species or incomplete lineage sorting due to rapid speciation might contribute to conflict topologies. The expanded gene families in C. indicum were associated with oxidative functions. Through comprehensive candidate gene screening, we identified five flavonoid O-methyltransferase (FOMT) candidates, which were highly expressed in flowers and whose expressional levels were significantly correlated with the content of acacetin. Further experiments validated two FOMTs (CI02A009970 and CI03A006662) were capable of catalyzing the conversion of apigenin into acacetin, and these two genes are possibly responsible acacetin accumulation in disc florets and young leaves, respectively. Furthermore, combined analyses of ancestral chromosome reconstruction and phylogenetic trees revealed the distinct evolutionary fates of the two validated FOMT genes. Our study provides new insights into the biosynthetic pathway of flavonoid compounds in the Asteraceae family and offers a model for tracing the origin and evolutionary routes of single genes. These findings will facilitate in vitro biosynthetic production of flavonoid compounds through cellular and metabolic engineering and expedite molecular breeding of C. indicum cultivars.

Non-invasive treatments improve patient outcomes in chronic tinnitus: a systematic review and network meta-analysis.

OBJECTIVE: To investigate the relative effectiveness of various Non-Invasive Treatment Techniques (NITs) in chronic tinnitus management. METHODS: We searched PubMed, Embase and Cochrane Library databases from the time of data construction to December 31, 2022. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, NITs were evaluated, including Aacceptance and commitment therapy (A), Cognitive behavioral therapy (C), Sound therapy (S), Transcranial magnetic stimulation (T), Electrical stimulation therapy (E), Virtual reality therapy (V), tinnitus Retraining therapy (R), general psychotherapy (D), and Placebo (P). The outcome indicators included the Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), Hospital Anxiety and Depression Scale-anxiety-Depression (HADS-D), Insomnia Severity Index (ISI), Visual Analogue Scales-Loudness (VAS-L), and Visual Analogue Scales-Distress (VAS-D). Statistical analysis was performed using Stata 14.0 for NMA. RESULTS: This systematic review and meta-analysis included 22 randomized controlled trials comprising 2,354 patients. The treatment effects varied on each scale. For THI, S (86.9%) was the most effective, whereas P (6.5%) was the worst. For TQ, C (89.5%) was the most effective, whereas D (25.4%) was the worst. For HADS-D, A (82.4%) was the most effective, whereas D (9.47%) was the worst. For ISI, A (83.2%) was the most effective, whereas R (20.6%) was the worst. For VAS-L, S (73.5%) was the most effective, whereas E (18.9%) was the worst. For VAS-D, C (84.7%) was the most effective, whereas P (18.1%) was the worst. CONCLUSIONS: The combination of acoustics and cognitive behavioral therapy may be an effectively treat patients with chronic tinnitus. LEVEL OF EVIDENCE: How common is the problem? Level 2. Is this diagnostic or monitoring test accurate? (Diagnosis) Level 1. What will happen if we do not add a therapy? (Prognosis) Level 1. Does this intervention help? (Treatment Benefits) Level 1. What are the COMMON harms? (Treatment Harms) Level 1. What are the RARE harms? (Treatment Harms) Level 1. Is this (early detection) test worthwhile? (Screening) Level 1I.

Hepatic artery restriction operation combined with ALPPS (HARO-ALPPS), a novel ALPPS procedure for the treatment of hepatocellular carcinoma with severe fibrosis: Retrospective clinical cohort study.

BACKGROUND: Associating liver partition with portal vein ligation for staged liver resection (ALPPS) has been used in the treatment of patients with advanced or massive liver cancer without sufficient future liver remnant, but concerns remain regarding tumor outcomes and surgical safety. This study aims to evaluate the efficacy and safety of a new procedure, Hepatic artery restriction operation combined with ALPPS (HARO-ALPPS), in the treatment of HCC patients especially with severe fibrosis. METHODS: This retrospective study analyzed 8 patients who underwent HARO-ALPPS for HCC and compared their outcomes with 64 patients who underwent conventional ALPPS. The primary outcomes assessed were liver regeneration ability (measured by relative and absolute kinetic growth rates), postoperative complications, and mortality. The secondary outcomes included overall survival and disease-free survival. RESULTS: HARO-ALPPS significantly restricted the blood supply of the hepatic artery. One week after surgery, the blood flow of the right hepatic artery dropped to 62.1%. At the same time, HARO-ALPPS shows superior liver regeneration ability, which is particularly prominent in the background of liver fibrosis. No serious complications occurred after HARO-ALPPS. The overall survival rate of HARO-ALPPS was 75%, which was higher than that of ALPPS (64%, P=0.816). CONCLUSION: Compared to conventional ALPPS, HARO-ALPPS exhibits a better liver regeneration ability, and favorable long-term outcomes. Further prospective studies are needed to validate these findings and evaluate the long-term oncologic outcomes of this novel procedure.

Methodological proposals for developing trustworthy recommendations of integrative Chinese-Western medicine.

Background: To refine the methods of developing clinical practice guidelines (CPGs) for integrative Chinese-Western medicine (ICWM), promoting the formation of trustworthy, implementable recommendations that integrate the strengths of Chinese and Western medicine. Methods: Using a nominal group technique (NGT) approach, a multidisciplinary expert panel was established. The panel identified key methodological issues in ICWM-CPG development through literature review and iterative discussions, and formulated methodological proposals to address these issues. The final set of proposals was achieved through consensus among the panel members. Results: The collaborative effort resulted in the identification of five pivotal methodological issues and the subsequent establishment of 22 specific recommendations. These encompass strict adherence to renowned standards, such as those proposed by the Institute of Medicine (IOM) and Guidelines International Network (G-I-N), the employment of methodologies like the GRADE approach and RIGHT statement, the strategic constitution of a balanced development group, the adept identification of ICWM-focused clinical inquiries, the nuanced integration of diverse evidence sources, and the detailed crafting of transparent, implementable recommendations. Conclusions: This study concentrates on the most crucial and prevalent methodological issues in ICWM-CPG development, proposing a series of recommendations. These suggestions result from a multidisciplinary expert consensus, aiming to provide methodological guidance for ICWM-CPG developers, building upon the current foundational methodologies.

Prevalence and risk factors of sarcopenia in patients on maintenance hemodialysis: a retrospective cohort study.

BACKGROUND: This study aimed to explore the prevalence and related risk factors of sarcopenia in patients on maintenance hemodialysis (MHD). METHODS: This cohort study enrolled 165 patients on MHD. The patients were divided into sarcopenia and non-sarcopenia groups based on the presence of sarcopenia or not. Sarcopenia was diagnosed according to the consensus of the Asian Sarcopenia Working Group that considers reduced muscle mass and decreased muscle strength (19). The muscle mass was measured using the multi-frequency bioelectrical impedance (Inbody260) and skeletal muscle index (SMI) was used: <7.0 kg/m2 (male); <5.7 kg/m2 (female) - with muscle mass reduction. The electronic grip dynamometer was used for measuring dominant handgrip strength (HGS) to reflect muscle strength. Male patients with HGS < 28 kg and female patients with HGS < 18 kg were considered with a decrease in muscle strength. The demographic characteristics, laboratory indexes, anthropometrical measurements, body compositions, and InBody score were compared between groups. The multivariate logistic regression was used to explore the risk factors for sarcopenia. RESULTS: Of the 165 patients on MHD, 36 had sarcopenia, and the prevalence was 21.82%. Patients in the sarcopenia group had higher ages and lower body mass index, serum albumin level, circumference of waist, hip, and biceps, handgrip strength, total water content, protein inorganic salt concentrations, skeletal muscle mass, basal metabolic rate, obesity degree, SMI, and body fat content. The multivariate logistic regression showed that age, waist circumference, handgrip strength, and InBody score were influencing factors for sarcopenia in patients on hemodialysis. CONCLUSION: The prevalence of sarcopenia was high in patients on MHD. Higher age, lower waist circumference, lower handgrip strength, and lower InBody score were independent risk factors for sarcopenia in such patients.

Changes in vegetation-water response in the Sahel-Sudan during recent decades.

Study region: The Africa Sahel-Sudan region, defined by annual rainfall between 150 and 1200 mm. Study focus: Understanding the mechanism of vegetation response to water availability could help mitigate the potential adverse effects of climate change on global dryland ecosystems. In the Sahel-Sudan region, spatio-temporal changes and drivers of the vegetation-water response remain unclear. This study employs long-term satellite water and vegetation products as proxies of water availability and vegetation productivity to analyze changes in vegetation-water sensitivity and the cumulative effect duration (CED) representing a measure of the legacy effect of the impact of water constraints on vegetation. A random forest model was subsequently used to analyze potential climatic drivers of the observed vegetation response. New hydrological insights for the region: During 1982-2016 we found a significant decrease (p < 0.05) in the sensitivity of vegetation productivity to water constraints in 26% of the Sahel-Sudan region, while 9% of the area showed a significantly increased sensitivity, mainly in the sub-humid zone. We further showed that CED significantly increased and decreased, respectively in around 9% of the study area in both cases. Our climatic driver attribution analysis suggested the existence of varying underlying mechanisms governing vegetation productivity in response to water deficit across the Sahel-Sudan dryland ecosystems. Our findings emphasize the need for diverse strategies in sustainable ecosystem management to effectively address these varying mechanisms.

Psychometric evaluation of the Chinese version of the burnout syndrome assessment scale in nurses.

Objective: This study aimed to translate the Burnout Syndrome Assessment Scale (BOSAS) into Chinese and validate its reliability and validity among Chinese emergency department and ICU nurses. Methods: The scale was translated into Chinese using Brislin's translation principle. A total of 626 nurses from Jiangxi, Zhejiang, and Fujian provinces in China participated in an online questionnaire survey. The survey included the general information questionnaire for nurses developed by the research team and the Chinese version of the Burnout Syndrome Assessment Scale. Reliability and validity of the Chinese version of the scale were analyzed using SPSS.25 and AMOS.24 software. Results: The Chinese version of the Burnout Syndrome Assessment Scale consists of a total of 20 items, encompassing two dimensions: personal burnout and job burnout. This structure is consistent with the original English version of the scale. The Chinese version of BOSAS demonstrated high internal consistency, with a Cronbach's α coefficient of 0.941. Additionally, the scale exhibited good split-half reliability (0.765) and test-retest reliability (0.871). The content validity index (S-CVI) was 0.971, indicating strong content validity. Exploratory factor analysis confirmed the same 2-factor structure as the original scale, and confirmatory factor analysis further validated this structure, with all fit indices indicating appropriateness. Conclusion: The Burnout Syndrome Assessment Scale has been successfully introduced and its reliability and validity have been verified in Chinese emergency department and ICU nurses.

Characterization of kombucha prepared from black tea and coffee leaves: A comparative analysis of physiochemical properties, bioactive components, and bioactivities.

The utilization of coffee leaves in kombucha production has intrigued researchers; however, the lack of understanding regarding the characteristics of coffee leaf kombucha (CK) and its differentiation from black tea kombucha (BK) has impeded its application in the beverage industry. Therefore, this study aimed to characterize and compare the physiochemical properties, phytochemical compositions, antioxidant activity, and α-glucosidase inhibitory ability of kombucha prepared from the leaves of Coffea arabica (CK) and black tea (Camellia sinensis, BK) and their extracts (CT and BT). After fermentation, pH and the contents of total sugars, reducing sugars, and free amino acids of BK and CK were decreased, whereas the levels of total acids and organic acids, such as gluconic, lactic, and acetic acid were increased. Notably, the concentration of vitamin C in CK was 48.9% higher than that in BK. HPLC analysis exhibited that 5-caffeoylquinic acid in CT was significantly decreased by 48.0% in CK, whereas the levels of 3-caffeoylquinic acid and 4-caffeoylquinic acid were significantly increased after fermentation. The content of caffeine was significantly (p < 0.05) reduced by 9.5% and 22.0% in BK and CK, respectively, whereas the theobromine level was significantly increased in CK. Notably, CK has superior total phenolic and flavonoid contents and antioxidant activity than BK, whereas BK possesses higher α-glucosidase inhibitory capacity. Electronic nose analysis demonstrated that sulfur-containing organics were the main volatiles in both kombuchas, and fermentation significantly increased their levels. Our study indicates that coffee leaves are a promising resource for preparing kombucha. PRACTICAL APPLICATION: This article investigates the differences in physicochemical properties, bioactive constituents, antioxidant activity, and α-glucosidase inhibitory activity of kombucha preparation from black tea and coffee leaves. We have found that after fermentation BK had brighter soup color and higher α-glucosidase inhibitory capacity, whereas CK had higher levels of total phenols, flavonoids, vitamin C, and antioxidants and lower contents of sugars. This study provides valuable information for the preparation of CK with high-quality attributes and antioxidant activity.

Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron.

BACKGROUNDAs Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early-stage infection in the respiratory tract. Thus, elucidating the prophylactic efficacy of NAbs via nasal spray addresses an important clinical need.METHODSThe applicable potential of a nasal spray cocktail containing 2 NAbs was characterized by testing its neutralizing potency, synergetic neutralizing mechanism, emergency protective and therapeutic efficacy in a hamster model, and pharmacokinetics/pharmacodynamic (PK/PD) in human nasal cavity.RESULTSThe 2 NAbs displayed broad neutralizing efficacy against Omicron, and they could structurally compensate each other in blocking the Spike-ACE2 interaction. When administrated through the intranasal mucosal route, this cocktail demonstrated profound efficacy in the emergency prevention in hamsters challenged with authentic Omicron BA.1. The investigator-initiated trial in healthy volunteers confirmed the safety and the PK/PD of the NAb cocktail delivered via nasal spray. Nasal samples from the participants receiving 4 administrations over a course of 16 hours demonstrated potent neutralization against Omicron BA.5 in an ex vivo pseudovirus neutralization assay.CONCLUSIONThese results demonstrate that the NAb cocktail nasal spray provides a good basis for clinical prophylactic efficacy against Omicron infections.TRIAL REGISTRATIONwww.chictr.org.cn, ChiCTR2200066525.FUNDINGThe National Science and Technology Major Project (2017ZX10202203), the National Key Research and Development Program of China (2018YFA0507100), Guangzhou National Laboratory (SRPG22-015), Lingang Laboratory (LG202101-01-07), Science and Technology Commission of Shanghai Municipality (YDZX20213100001556), and the Emergency Project from the Science & Technology Commission of Chongqing (cstc2021jscx-fyzxX0001).

Current strategies for targeting HPK1 in cancer and the barriers to preclinical progress.

INTRODUCTION: Hematopoietic progenitor kinase 1 (HPK1), a 97-kDa serine/threonine Ste20-related protein kinase, functions as an intracellular negative regulator, primarily in hematopoietic lineage cells, where it regulates T cells, B cells, dendritic cells, and other immune cells. Loss of HPK1 kinase activity results in exacerbated cytokine secretion, enhanced T cell signaling, improved viral clearance, and thus increased restraint of tumor growth. These findings highlight HPK1 as a promising target for immuno-oncology treatments, culminating in the advancement of candidate compounds targeting HPK1 to clinical trials by several biotech enterprises. AREAS COVERED: Through searching PubMed, Espacenet-patent search, and clinicaltrials.gov, this review provides a comprehensive analysis of HPK1, encompassing its structure and roles in various downstream signaling pathways, the consequences of constitutive activation of HPK1, and potential therapeutic strategies to treat HPK1-driven malignancies. Moreover, the review outlines the patents issued for small molecule inhibitors and clinical investigations of HPK1. EXPERT OPINION: To enhance the success of tumor immunotherapy in clinical trials, it is important to develop protein degraders, allosteric inhibitors, and antibody-drug conjugates based on the crystal structure of HPK1, and to explore combination therapy approaches. Although several challenges remain, the development of HPK1 inhibitors display promising in preclinical and clinical studies.

Neurodevelopmental disorders as a risk factor for temporomandibular disorder: evidence from Mendelian randomization studies.

Objective: This study aims to clarify the incidence rate of temporomandibular joint disease in patients with mental disorders. Methods: Data extracted from the Psychiatric Genomics Consortium and FinnGen databases employed the Mendelian Randomization (MR) method to assess the associations of three neurodevelopmental disorders (NDDs)-Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette's Disorder (TD)-as exposure factors with Temporomandibular Disorder (TMD). The analysis used a two-sample MR design, employing the Inverse Variance Weighted (IVW) method to evaluate the relationships between these disorders and Temporomandibular Disorder. Sensitivity analysis and heterogeneity assessments were conducted. Potential confounding factors like low birth weight, childhood obesity, and body mass index were controlled for. Results: The study found that ADHD significantly increased the risks for TMD (OR = 1.2342, 95%CI (1.1448-1.3307), p < 0.00001), TMD (including avohilmo) (OR = 1.1244, 95%CI (1.0643-1.1880), p = 0.00003), TMD-related pain (OR = 1.1590, 95%CI (1.0964-1.2252), p < 0.00001), and TMD-related muscular pain associated with fibromyalgia (OR = 1.1815, 95%CI (1.1133-1.2538), p < 0.00001), while other disorders did not show significant causal relationships. Conclusion: This study reveals the elevated risk of various TMD aspects due to ADHD. Furthermore, we discuss the link between low vitamin D levels ADHD and TMD. Future research should address these limitations and delve further into the complex interactions between ADHD, ASD, TD, and TMD.

Dynamics of extrachromosomal circular DNA in rice.

The genome's dynamic nature, exemplified by elements like extrachromosomal circular DNA (eccDNA), is crucial for biodiversity and adaptation. Yet, the role of eccDNA in plants, particularly rice, remains underexplored. Here, we identify 25,598 eccDNAs, unveiling the widespread presence of eccDNA across six rice tissues and revealing its formation as a universal and random process. Interestingly, we discover that direct repeats play a pivotal role in eccDNA formation, pointing to a unique origin mechanism. Despite eccDNA's prevalence in coding sequences, its impact on gene expression is minimal, implying its roles beyond gene regulation. We also observe the association between eccDNA's formation and minor chromosomal deletions, providing insights of its possible function in regulating genome stability. Further, we discover eccDNA specifically accumulated in rice leaves, which may be associated with DNA damage caused by environmental stressors like intense light. In summary, our research advances understanding of eccDNA's role in the genomic architecture and offers valuable insights for rice cultivation and breeding.

Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx.

To date, several molecules have been found to facilitate iron influx, while the types of iron influx channels remain to be elucidated. Here, Piezo1 channel was identified as a key iron transporter in response to mechanical stress. Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells (NPCs). Importantly, Piezo1-induced iron influx was independent of the transferrin receptor (TFRC), a well-recognized iron gatekeeper. Furthermore, pharmacological inactivation of Piezo1 profoundly reduced iron accumulation, alleviated mitochondrial ROS, and suppressed ferroptotic alterations in stimulation of mechanical stress. Moreover, conditional knockout of Piezo1 (Col2a1-CreERT Piezo1flox/flox) attenuated the mechanical injury-induced intervertebral disc degeneration (IVDD). Notably, the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout (cDKO) mice (Col2a1-CreERT Piezo1flox/flox/Gpx4flox/flox). These findings suggest that Piezo1 is a potential determinant of iron influx, indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

Reporting quality of acupuncture overviews: A methodological investigation based on the PRIOR statement.

OBJECTIVE: Acupuncture overviews are increasing rapidly; however, their reporting quality is yet unclear. We aimed to investigate the reporting quality of relevant overviews according to the preferred reporting items for overviews of reviews (PRIOR) statement. METHODS: We systematically searched PubMed from inception to August 16, 2022 for overviews on acupuncture therapies. Reporting quality of included overviews was evaluated using the PRIOR statement, and the results were cross-checked. Multiple linear regression analysis was used to assess the predictors of the reporting completeness. GraphPad 9.4 was utilized to generate an evidence map, Excel 2019 was used to extract and manage data, and R 4.2.3 was used for data analysis. RESULTS: A total of 49 overviews published from 2006 to 2022 were included, of which China ranked first with 38 overviews. The most frequently searched database was PubMed/ Medline (n = 48, 98%), and commonly used methodological quality assessment tool was AMSTAR-2 (n = 14, 29%). The overarching themes centered on acupuncture for obstetrics, gynecology, reproductive diseases, as well as depression, anxiety, and insomnia. Reporting quality needs to be improved involving the definition of systematic reviews (SRs), overlap of primary studies and SRs, methods for managing discrepant data across SRs, risk of bias in primary studies, heterogeneity, and sensitivity analysis of synthesized results, reporting bias assessment, and registration and protocol. Moreover, publication in recent years and receiving funding support were significantly associated with higher overall reporting quality score (P < 0.05). CONCLUSION: Based on the PRIOR statement, this methodological study indicates that the reporting quality of the included acupuncture overviews is poor. In the future, authors of overviews are encouraged to use the PRIOR statement for standardized reporting. Furthermore, it is recommended that journal editors mandate the inclusion of this statement in authors' reports and require a complete PRIOR checklist.

Left Hepatectomy Combined with Right Hepatic Artery Resection and Reconstruction for Hilar Cholangiocarcinoma.

BACKGROUND: Hepatectomy combined with hepatic artery reconstruction in the operation for hilar cholangiocarcinoma (Klatskin tumor) is a challenging procedure. We present a video of left hepatectomy combined with right hepatic artery reconstruction for hilar cholangiocarcinoma. PATIENT AND METHODS: The patient was a 60-year-old male who presented with obstructive jaundice. The imaging examination showed that the confluence of left and right hepatic ducts and the wall of common hepatic duct were thickened, the local lumen was narrowed, the intrahepatic bile duct was dilated, and the right hepatic artery was invaded by tumors nearly 2.3 centimeters. Left hepatectomy with total caudate lobectomy, resection with reconstruction of right hepatic artery, hilar lymphadenectomy, and Roux-en-Y hepaticojejunostomy were performed. RESULTS: The operation time was 345 min, and the amount of bleeding was about 400 ml. There was no blood transfusion. The pathology showed poorly differentiated adenocarcinoma, with negative margins of common bile duct and right hepatic duct, and negative results of all lymph nodes. The patient's recovery was uneventful and he was discharged on postoperative day 14. The patient was disease free at 12-month follow-up evaluation. CONCLUSIONS: Hepatic artery resection and reconstruction procedure is safe and feasible for hilar cholangiocarcinoma in a highly tertiary hepatobiliary center.

Chronic diseases spectrum and multimorbidity in elderly inpatients based on a 12-year epidemiological survey in China.

BACKGROUND: The number and proportion of the elderly population have been continuously increasing in China, leading to the elevated prevalence of chronic diseases and multimorbidity, which ultimately brings heavy burden to society and families. Meanwhile, the status of multimorbidity tends to be more complex in elderly inpatients than community population. In view of the above concerns, this study was designed to investigate the health status of elderly inpatients by analyzing clinical data in Chinese People's Liberation Army (PLA) General Hospital from 2008 to 2019, including the constitution of common diseases, comorbidities, the status of multimorbidity, in-hospital death and polypharmacy among elderly inpatients, so as to better understand the diseases spectrum and multimorbidity of elderly inpatients and also to provide supporting evidence for targeted management of chronic diseases in the elderly. METHODS: A clinical inpatients database was set up by collecting medical records of elderly inpatients from 2008 to 2019 in Chinese PLA General Hospital, focusing on diseases spectrum and characteristics of elderly inpatients. In this study, we collected data of inpatients aged ≥ 65 years old, and further analyzed the constitution of diseases, multimorbidity rates and mortality causes in the past decade. In addition, the prescriptions were also analyzed to investigate the status of polypharmacy in elderly inpatients. RESULTS: A total of 210,169 elderly patients were hospitalized from January 1st, 2008 to December 31st, 2019. The corresponding number of hospitalizations was 290,833. The average age of the study population was 72.67 years old. Of the total population, 73,493 elderly patients were re-admitted within one year, with the re-hospitalization rate of 25.27%. Malignant tumor, hypertension, ischemic heart disease, diabetes mellitus and cerebrovascular disease were the top 5 diseases. Among the study population, the number of patients with two or more long-term health conditions was 267,259, accounting for 91.89%, with an average of 4.68 diseases. In addition, the average number of medications taken by the study population was 5.4, among which, the proportion of patients taking more than 5 types of medications accounted for 55.42%. CONCLUSIONS: By analyzing the constitution of diseases and multimorbidity, we found that multimorbidity has turned out to be a prominent problem in elderly inpatients, greatly affecting the process of healthy aging and increasing the burden on families and society. Therefore, multidisciplinary treatment should be strengthened to make reasonable preventive and therapeutic strategies to improve the life quality of the elderly. Meanwhile, more attention should be paid to reasonable medications for elderly patients with multimorbidity to avoid preventable side effects caused by irrational medication therapy.

Comparison of Clinical Characteristics, Therapy, and Short-Term Prognosis between Blunt and Penetrating Abdominal Trauma: A Multicentric Retrospective Cohort Study.

Objective: Large-scale studies on the characteristics and management of abdominal trauma in megacities in China are lacking. The aim of this study was to analyze and present the clinical patterns and treatment status of abdominal trauma in regional medical centers. Methods: Cases of abdominal trauma treated at seven medical centers in Beijing from 2010 to 2021 were collected. Clinical information about age, sex, injury cause, geographic distribution, abbreviated injury scale/injury severity score (AIS/ISS) value, injury-hospital time, preoperative time, surgically identified organ injuries, type of surgery, causes of reoperation and 90-day mortality was included in this study. Clinical characteristics, treatment methods, and short-term prognoses (90-days survival) were compared between blunt abdominal trauma (BAT) and penetrating abdominal trauma (PAT) cases. Non-normally distributed data are described as medians (IQR), and the Mann‒Whitney U test was performed; qualitative data were analyzed using the X2 test. Univariate and multivariate survival analyses were performed by the Cox proportional hazards model. Results: A total of 553 patients (86.98% male) with a median age of 36.50 (27.00-48.00) years were included. The BAT group had a significantly higher proportion of serious injury (P=0.001), lower initial hemoglobin level (P=0.001), and a lower laparoscopy surgery rate (P=0.044) compared to the PAT group. Additionally, more BAT cases were from the area around Beijing (P=0.008) and a longer injury-regional hospital time (10.47 (5.18-22.51) hours vs. 7.00 (3.80-15.38) hours, P=0.001). In the hollow viscus injury subgroup, the BAT group had a significantly longer injury-regional hospital time and preoperative time compared to the PAT group (injury-regional hospital time: 10.23 (6.00-21.59) hours vs. 7.07 (3.99-13.85) hours, P=0.002; preoperative time: 3.02 (2.01-5.58) hours vs. 2.81 (1.85-3.63) hours, P=0.047). The overall 90-day mortality was 11.9%, and longer injury-regional hospital time (HR: 1.01, 95% CI: 1.00-1.02, P=0.008), receipt of ICU treatment (HR: 4.69, 95% CI: 2.54-8.65, P=0.001), and severe ISSs (ISS > 25 vs. ISS < 16, HR: 2.78, 95% CI: 1.38-5.601, P=0.004) had a worse impact on survival. Conclusion: More patients with BAT were transferred to higher-level hospital, leading to significantly longer prehospital and preoperation time. In the subgroup of hemodynamically stable individuals, more patients with BAT experienced hollow viscus injuries. For those patients, aggressive diagnostic laparoscopic exploration may be beneficial. Patients with longer injury-regional hospital intervals, the need for ICU care, and higher injury severity scores (ISSs) suffered from worse prognoses.

Prenatal exposures to phthalates and bisphenols in relation to oxidative stress: single pollutant and mixtures analyses.

Prenatal exposures to phthalates and bisphenols have been shown to be linked with adverse birth outcomes. Oxidative stress (OS) is considered a potential mechanism. The objective of this study was to explore the individual and mixtures of prenatal exposures to phthalates and bisphenols in associations with OS biomarkers. We measured eight phthalate metabolites and three bisphenols in the urine samples from 105 pregnant women in Wuhan, China. Urinary 8-hydroxydeoxyguanosine (8-OHdG), 8-isoprostaglandin F2α (8-isoPGF2α), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) were determined as OS biomarkers. The OS biomarkers in associations with the individual chemicals were estimated by linear regression models and restricted cubic spline (RCS) models, and their associations with the chemical mixtures were explored by quantile g-computation (qg-comp) models. In single-pollutant analyses, five phthalate metabolites including monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-(2-ethylhexyl) phthalate (MEHP), (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were positively associated with urinary 8-OHdG levels (all FDR-adjusted P = 0.06). These associations were further confirmed by the RCS models and were linear (P for overall association ≤ 0.05 and P for non-linear association > 0.05). In mixture analyses, qg-comp models showed that a one-quartile increase in the chemical mixtures of phthalate metabolites and bisphenols was positively associated with urinary levels of 8-OHdG and 8-isoPGF2α, and bisphenol A (BPA) and bisphenol F (BPF) were the most contributing chemicals, respectively. Prenatal exposures to individual phthalates and mixtures of phthalates and bisphenols were associated with higher OS levels.