Statin therapy enhances survival in unresectable stage III lung squamous cell carcinoma with concurrent chemoradiotherapy.

To evaluate the impact of statin use on overall survival and lung cancer-specific survival in patients with unresectable stage III lung squamous cell carcinoma (LSCC) undergoing standard concurrent chemoradiotherapy (CCRT). Using data from the Taiwan Cancer Registry Database and National Health Insurance Research Database, this propensity score matching cohort study analyzed the influence of statin use during CCRT on overall survival and lung cancer-specific survival. Statin use during CCRT was independently associated with significant improvements in overall survival and lung cancer-specific survival. The adjusted hazard ratio (95% CI) for all-cause mortality in the statin group versus the non-statin group was 0.60 (0.53-0.68, P < 0.0001). Similarly, the adjusted hazard ratio for lung cancer-specific mortality in the statin group versus the non-statin group was 0.61 (95% CI, 0.54-0.70, P < 0.0001). Pravastatin and fluvastatin exhibited the greatest potential in reducing lung cancer-specific mortality among statins, with rosuvastatin following closely behind. Atorvastatin demonstrated comparable effectiveness, while simvastatin and lovastatin displayed lower efficacy in this regard. Furthermore, a dose-response relationship was observed, with higher cumulative defined daily doses and greater daily intensity of statin use associated with reduced mortality. Our study provides evidence that statin use during CCRT for unresectable stage III LSCC is associated with significant improvements in overall survival and lung cancer-specific survival. Pravastatin showed the highest potential for reducing lung cancer-specific mortality among statins, followed by rosuvastatin. Atorvastatin and fluvastatin exhibited similar effectiveness, while simvastatin and lovastatin demonstrated lower efficacy. The dose-response relationship showed higher statin utilization in reducing lung cancer-specific mortality.

Analyzing the correlation between low proportion of hobnail features in papillary thyroid carcinoma and clinical aggressiveness risk.

PURPOSE: Hobnail features may enhance the clinical aggressiveness of papillary thyroid carcinoma (PTC). However, whether a low proportion (<30%) of these features contributes to increased PTC aggressiveness remains unclear. This study investigated whether PTC cases with a low proportion hobnail features (<30%) exhibit clinical invasiveness and pathological features of aggressiveness. METHODS: Pathological specimens from patients with postoperatively diagnosed PTC were retrospectively analyzed. Among them, 29 PTC cases with a low proportion of hobnail features (<30%) were compared with 173 consecutive classical PTC (cPTC) cases. Data regarding age at presentation, sex, tumor size, number of tumors, and histological characteristics were obtained by reviewing electronic medical records. Postoperative information was obtained during follow-up visits and telephone interviews. RESULTS: Twenty-nine patients with PTC with a low proportion of hobnail features (<30%) were identified, exhibiting a median age of 34 years. At a median follow-up of 31 (IQR, 23-37) months, two patients had recurrent disease in the PTC with a low proportion of hobnail features (<30%) group, whereas there was no recurrence in the cPTC group. No distant metastasis and postoperative mortality were observed in either group. Compared with the cPTC group, patients with PTC and a low proportion of hobnail features exhibited larger tumor volumes and higher susceptibility to capsular invasion and lymph node metastasis. Tumor size and hobnail features emerged as independent risk factors for lymph node metastasis. CONCLUSION: PTC with a low proportion hobnail features (<30%) and larger tumor volumes are associated with the occurrence of lymph node metastasis. A low proportion of hobnail features (<30%) in PTC may heighten invasiveness, elevating the risk of recurrence.

Ubiquitin-induced RNF168 condensation promotes DNA double-strand break repair.

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.

Adverse postoperative outcomes in elderly patients with sarcopenia.

PURPOSE: No study has compared 30-day and 90-day adverse postoperative outcomes between old-age patients with and those without sarcopenia. PATIENTS AND METHODS: We categorize elderly patients receiving major surgery into two groups according to the presence or absence of preoperative sarcopenia that were matched at a 1:4 ratio through propensity score matching (PSM). We analyzed 30-day or 90-day adverse postoperative outcomes and mortality in patients with and without sarcopenia receiving major surgery. RESULTS: Multivariate logistic regression analyses revealed that the patients with preoperative sarcopenia were at significantly higher risk of 30-day postoperative mortality (adjusted odds ratio [aOR]. = 1.25; 95% confidence interval [CI]. = 1.03-1.52) and 30-day major complications such as postoperative pneumonia (aOR = 1.15; 95% CI = 1.00-1.40), postoperative bleeding (aOR = 2.18; 95% CI = 1.04-4.57), septicemia (aOR = 1.31; 95% CI = 1.03-1.66), and overall complications (aOR = 1.13; 95% CI = 1.00-1.46). In addition, surgical patients with sarcopenia were at significantly higher risk of 90-day postoperative mortality (aOR = 1.50; 95% CI = 1.29-1.74) and 90-day major complications such as pneumonia (aOR = 1.27; 95% CI = 1.10-1.47), postoperative bleeding (aOR = 1.90; 95% CI = 1.04-3.48), septicemia (aOR = 1.52; 95% CI = 1.28-1.82), and overall complications (aOR = 1.24; 95% CI = 1.08-1.42). CONCLUSIONS: Sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes such as pneumonia, postoperative bleeding, and septicemia and increases 30-day and 90-day postoperative mortality among patients receiving major surgery. No study has compared 30-day and 90-day adverse postoperative outcomes between patients with and those without sarcopenia. We conducted a propensity score?matched (PSM) population-based cohort study to investigate the adverse postoperative outcomes and mortality in patients undergoing major elective surgery with preoperative sarcopenia versus those without preoperative sarcopenia. We demonstrated that sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes, such as postoperative pneumonia, bleeding, septicemia, and mortality after major surgery. Therefore, surgeons and anesthesiologists should attempt to correct preoperative sarcopenia, swallowing function, and respiratory muscle training before elective surgery to reduce postoperative complications that contribute to the decrease in surgical mortality.

Maintenance chemotherapy for esophageal squamous cell carcinoma after standard concurrent chemoradiotherapy: a national propensity score matching cohort study.

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive cancer, and its standard treatment is concurrent chemoradiotherapy (CCRT). Maintenance chemotherapy is often used to help prevent cancer recurrence, but its efficacy for patients with ESCC receiving CCRT remains unclear. We conducted a large head-to-head propensity score matching cohort study to estimate the effects of maintenance chemotherapy on overall survival and cancer-specific survival in patients with ESCC receiving standard CCRT. After propensity score matching (PSM), we recruited 2724 patients with ESCC (2177 in the maintenance chemotherapy group and 547 in the non-maintenance chemotherapy group). The adjusted hazard ratios (95% confidence intervals) of all-cause mortality and cancer-specific mortality for the maintenance chemotherapy group were 1.15 (1.06-1.26, P = 0.0014) and 1.08 (0.88-1.29, P = 0.1320), respectively, compared with the non-maintenance chemotherapy group. We also found that older age, relatively lower body mass index (BMI), higher American Joint Committee on Cancer clinical stage, and poor response to CCRT as measured using the Response Evaluation Criteria in Solid Tumors were poor independent predictors of all-cause mortality and cancer-specific mortality. Our findings indicated that maintenance chemotherapy may not improve the survival of patients with ESCC who have received CCRT. Additionally, we identified several key prognostic factors for patients with ESCC receiving CCRT, including relatively low BMI and poor response to CCRT. Further research is needed to understand the benefits and risks of maintenance chemotherapy in similar patient populations in order to identify new therapies that could improve treatment responses.

Correlation of maintenance chemotherapy and improved survival in patients with locally advanced unresectable pancreatic head adenocarcinoma receiving neoadjuvant chemotherapy and concurrent chemoradiotherapy.

To assess the efficacy of maintenance chemotherapy in the management of unresectable locally advanced pancreatic head adenocarcinoma (PHA) cancer after neoadjuvant chemotherapy and concurrent chemoradiation therapy (CCRT). This study, a large-scale head-to-head propensity score matching (PSM) cohort study, employed real-world data. PSM was used to evaluate the impact of maintenance chemotherapy on overall survival and cancer-specific survival in patients with unresectable locally advanced PHA who underwent neoadjuvant chemotherapy and CCRT. A total of 148 patients with locally advanced pancreatic head adenocarcinoma were included in the study after PSM. These patients were equally divided into two groups, those receiving maintenance chemotherapy and those who did not. Confounding factors were balanced between the groups. The adjusted hazard ratios for all-cause mortality and cancer-specific mortality were 0.56 (95% CI: 0.40-0.77; P = 0.0005) and 0.56 (95% CI: 0.40-0.78; P = 0.0007), respectively, in patients receiving maintenance chemotherapy compared to those who did not. Our large-scale, real-world study demonstrates that maintenance chemotherapy may enhance survival outcomes for patients with unresectable locally advanced pancreatic head adenocarcinoma who underwent neoadjuvant chemotherapy and concurrent chemoradiation therapy.

Human-Derived Induced GABAergic Progenitor Cells Improve Cognitive Function in Mice and Inhibit Astrocyte Activation with Anti-Inflammatory Exosomes.

OBJECTIVE: The role of gamma-aminobutyric acid-ergic (GABAergic) neuron impairment in Alzheimer's disease (AD), and if and how transplantation of healthy GABAergic neurons can improve AD, remain unknown. METHODS: Human-derived medial ganglionic eminence progenitors (hiMGEs) differentiated from programmed induced neural precursor cells (hiNPCs) were injected into the dentate gyrus region of the hippocampus (HIP). RESULTS: We showed that grafts migrate to the whole brain and form functional synaptic connections in amyloid precursor protein gene/ presenilin-1 (APP/PS1) chimeric mice. Following transplantation of hiMGEs, behavioral deficits and AD-related pathology were alleviated and defective neurons were repaired. Notably, exosomes secreted from hiMGEs, which are rich in anti-inflammatory miRNA, inhibited astrocyte activation in vitro and in vivo, and the mechanism was related to regulation of CD4+ Th1 cells mediated tumor necrosis factor (TNF) pathway. INTERPRETATION: Taken together, these findings support the hypothesis that hiMGEs transplantation is an alternative treatment for neuronal loss in AD and demonstrate that exosomes with anti-inflammatory activity derived from hiMGEs are important factors for graft survival. ANN NEUROL 2024.

Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension.

BACKGROUNDS & AIMS: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH. METHODS: PH models were induced by thioacetamide injection, bile duct ligation, or partial PV ligation. HTR1A expression was detected using real-time polymerase chain reaction, in situ hybridization, and immunofluorescence staining. In situ intraportal infusion was used to assess the effects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1A antagonist WAY-100635 on portal pressure (PP). Htr1a-knockout (Htr1a-/-) rats and vascular smooth muscle cell (VSMC)-specific Htr1a-knockout (Htr1aΔVSMC) mice were used to confirm the regulatory role of HTR1A on PP. RESULTS: HTR1A expression was significantly increased in the hypertensive PV of PH model rats and cirrhotic patients. Additionally, 8-OH-DPAT increased, but WAY-100635 decreased, the PP in rats without affecting liver fibrosis and systemic hemodynamics. Furthermore, 5-HT or 8-OH-DPAT directly induced the contraction of isolated PVs. Genetic deletion of Htr1a in rats and VSMC-specific Htr1a knockout in mice prevented the development of PH. Moreover, 5-HT triggered adenosine 3',5'-cyclic monophosphate pathway-mediated PV smooth muscle cell contraction via HTR1A in the PV. We also confirmed alverine as an HTR1A antagonist and demonstrated its capacity to decrease PP in rats with thioacetamide-, bile duct ligation-, and partial PV ligation-induced PH. CONCLUSIONS: Our findings reveal that 5-HT promotes PH by inducing the contraction of the PV and identify HTR1A as a promising therapeutic target for attenuating PH. As an HTR1A antagonist, alverine is expected to become a candidate for clinical PH treatment.

Molecular docking and MD simulation studies of 4-thiazol-N-(pyridin-2-yl)pyrimidin-2-amine derivatives as novel inhibitors targeted to CDK2/4/6.

PURPOSE: Nowadays, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have been approved for treating metastatic breast cancer and have achieved inspiring curative effects. But some discoveries have indicated that CDK 4/6 are not the requisite factors in some cell types because CDK2 partly compensates for the inhibition of CDK4/6. Thus, it is urgent to design CDK2/4/6 inhibitors for significantly enhancing their potency. This study aims to explore the mechanism of the binding of CDK2/4/6 kinases and their inhibitors to design novel CDK2/4/6 inhibitors for significantly enhancing their potency in different kinds of cancers. MATERIALS AND METHODS: A series of 72 disparately functionalized 4-substituted N-phenylpyrimidin-2-amine derivatives exhibiting potent inhibitor activities against CDK2, CDK4 and CDK6 were collected to apply to this research. The total set of these derivatives was divided into a training set (54 compounds) and a test set (18 compounds). The derivatives were constructed through the sketch molecule module in SYBYL 6.9 software. A Powell gradient algorithm and Tripos force field were used to calculate the minimal structural energy and the minimized structure was used as the initial conformation for molecular docking. By the means of 3D-QSAR models, partial least squares (PLS) analysis, molecular dynamics (MD) simulations and binding free energy calculations, we can find the relationship between structure and biological activity. RESULTS: In this study, we used molecular docking, 3D-QSAR and molecular dynamics simulation methods to comprehensively analyze the interaction and structure-activity relationships of 72 new CDK2/4/6 inhibitors. We used detailed statistical data to reasonably verify the constructed 3D-QSAR models for three receptors (q2 of CDK2 = 0.714, R2pred = 0.764, q2 = 0.815; R2pred of CDK4 = 0.681, q2 = 0.757; R2pred of CDK6 = 0.674). MD simulations and decomposition energy analysis validated the reasonability of the docking results and identified polar interactions as crucial factors that influence the different bioactivities of the studied inhibitors of CDK2/4/6 receptors, especially the electrostatic interactions of Lys33/35/43 and Asp145/158/163. The nonpolar interaction with Ile10/12/19 was also critical for the differing potencies of the CDK2/4/6 inhibitors. We concluded that the following probably enhanced the bioactivity against CDK2/4/6 kinases: (1) electronegative groups at the N1-position and electropositive and moderate-sized groups at ring E; (2) electrogroups featured at R2; (3) carbon atoms at the X-position or ring C replaced by a benzene ring; and (4) an electrogroup as R4. CONCLUSION: Previous studies, to our knowledge, only utilized a single approach of 3D-QSAR and did not integrate this method with other sophisticated techniques such as molecular dynamics simulations to discover new potential inhibitors of CDK2, CDK4, or CDK6. So we applied the intergenerational technology, such as 3D-QSAR technology, molecular docking simulation techniques, molecular dynamics simulations and MMPBSA19/MMGBSA20-binding free energy calculations to statistically explore the correlations between the structure with biological activities. The constructed 3D-QSAR models of the three receptors were reasonable and confirmed by the excellent statistical data. We hope the results obtained from this work will provide some useful references for the development of novel CDK2/4/6 inhibitors.

Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives.

Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.

Thermostability-assisted limited proteolysis-coupled mass spectrometry for capturing drug target proteins and sites.

BACKGROUND: Identifying drug-binding targets and their corresponding sites is crucial for drug discovery and mechanism studies. Limited proteolysis-coupled mass spectrometry (LiP-MS) is a sophisticated method used for the detection of compound and protein interactions. However, in some cases, LiP-MS cannot identify the target proteins due to the small structure changes or the lack of enrichment of low-abundant protein. To overcome this drawback, we developed a thermostability-assisted limited proteolysis-coupled mass spectrometry (TALiP-MS) approach for efficient drug target discovery. RESULTS: We proved that the novel strategy, TALiP-MS, could efficiently identify target proteins of various ligands, including cyclosporin A (a calcineurin inhibitor), geldanamycin (an HSP90 inhibitor), and staurosporine (a kinase inhibitor), with accurately recognizing drug-binding domains. The TALiP protocol increased the number of target peptides detected in LiP-MS experiments by 2- to 8-fold. Meanwhile, the TALiP-MS approach can not only identify both ligand-binding stability and destabilization proteins but also shows high complementarity with the thermal proteome profiling (TPP) and machine learning-based limited proteolysis (LiP-Quant) methods. The developed TALiP-MS approach was applied to identify the target proteins of celastrol (CEL), a natural product known for its strong antioxidant and anti-cancer angiogenesis effect. Among them, four proteins, MTHFD1, UBA1, ACLY, and SND1 were further validated for their strong affinity to CEL by using cellular thermal shift assay. Additionally, the destabilized proteins induced by CEL such as TAGLN2 and CFL1 were also validated. SIGNIFICANCE: Collectively, these findings underscore the efficacy of the TALiP-MS method for identifying drug targets, elucidating binding sites, and even detecting drug-induced conformational changes in target proteins in complex proteomes.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer.

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

Association between postoperative hyperactive delirium and major complications in elderly patients undergoing emergency hip fracture surgery: A large-scale cohort study.

AIM: This cohort study aimed to explore the connection between postoperative hyperactive delirium and major complications in elderly patients undergoing emergency hip fracture surgery. METHODS: Elderly patients aged 65 years and older undergoing emergency hip fracture surgery were included in the study. The presence of postoperative hyperactive delirium was assessed, and logistic regression analysis, following propensity score matching, was conducted to investigate the association between postoperative hyperactive delirium and major complications occurring 30 and 90 days post-surgery. The analysis controlled for potential confounding factors. RESULTS: After propensity score matching, the analysis included 13 590 patients, equally distributed with 6795 in each group. The group experiencing postoperative hyperactive delirium exhibited a significantly elevated risk of 30-day postoperative complications, including acute renal failure, pneumonia, septicemia, and stroke, with adjusted odds ratios ranging from 1.64 to 2.39. Furthermore, this group displayed notably higher rates of 90-day postoperative complications, encompassing mortality, acute renal failure, pneumonia, septicemia, and stroke, with a significantly increased incidence of mortality within 90 days. CONCLUSION: Postoperative hyperactive delirium in elderly patients undergoing emergency hip fracture surgery is significantly linked to an increased risk of major complications at both 30 and 90 days post-surgery. These findings underscore the critical importance of delirium prevention and management in this patient population, offering the potential to reduce the occurrence of postoperative complications. Geriatr Gerontol Int 2024; 24: 730-736.

Ketogenic diet induces p53-dependent cellular senescence in multiple organs.

A ketogenic diet (KD) is a high-fat, low-carbohydrate diet that leads to the generation of ketones. While KDs improve certain health conditions and are popular for weight loss, detrimental effects have also been reported. Here, we show mice on two different KDs and, at different ages, induce cellular senescence in multiple organs, including the heart and kidney. This effect is mediated through adenosine monophosphate-activated protein kinase (AMPK) and inactivation of mouse double minute 2 (MDM2) by caspase-2, leading to p53 accumulation and p21 induction. This was established using p53 and caspase-2 knockout mice and inhibitors to AMPK, p21, and caspase-2. In addition, senescence-associated secretory phenotype biomarkers were elevated in serum from mice on a KD and in plasma samples from patients on a KD clinical trial. Cellular senescence was eliminated by a senolytic and prevented by an intermittent KD. These results have important clinical implications, suggesting that the effects of a KD are contextual and likely require individual optimization.

Yiwei Xiaoyu granules for treatment of chronic atrophic gastritis with deficiency syndrome of the spleen and stomach.

BACKGROUND: The Correa sequence, initiated by Helicobacter pylori (H. pylori), commonly progresses to gastric cancer through the stage of chronic atrophic gastritis (CAG). Although eradication of H. pylori only reduces the risk of gastric cancer, it does not eliminate the risk for neoplastic progression. Yiwei Xiaoyu granules (YWXY) are a commonly used composite preparation in Chinese clinics. However, the pursuit of excellence in clinical trials and the establishment of standardized animal experiments are still needed to contribute to full understanding and application of traditional Chinese medicine in the treatment of CAG. AIM: To demonstrate the effectiveness of YWXY in patients with CAG and spleen-stomach deficiency syndrome (DSSS), by alleviating histological scores, improving response rates for pathological lesions, and achieving clinical efficacy in relieving DSSS symptoms. METHODS: We designed a double-blind, randomized, controlled trial. The study enrolled seventy-two H. pylori-negative patients (mean age, 52.3 years; 38 men) who were randomly allocated to either the treatment group or control group in a 1:1 ratio, and treated with 15 g YWXY or 0.36 g Weifuchun (WFC) tablet combined with the respective dummy for 24 wk. The pre-randomization phase resulted in the exclusion of 72 patients: 50 participants did not meet the inclusion criteria, 12 participants declined to participate, and 10 participants were excluded for various other reasons. Seven visits were conducted during the study, and histopathological examination with target endoscopic biopsy of narrow-band imaging was requested before the first and seventh visits. We also evaluated endoscopic performance scores, total symptom scores, serum pepsinogen and gastrin-17. RESULTS: Six patients did not complete the trial procedures. Treatment with YWXY improved the Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stage, compared with WFC (P < 0.05). YWXY provided better relief from symptoms of DSSS and better improvement in serum gastric function, compared with WFC (P < 0.05). CONCLUSION: YWXY compared with WFC significantly reduced the risk of mild or moderate atrophic disease, according to OLGIM stage, significantly relieved symptoms of DSSS, and improved serum gastric function.

Postoperative myopic shift and visual acuity rehabilitation in patients with bilateral congenital cataracts.

Background: This study aimed to explore the postoperative myopic shift and its relationship to visual acuity rehabilitation in patients with bilateral congenital cataracts (CCs). Methods: Bilateral CC patients who underwent cataract extraction and primary intraocular lens implantations before 6 years old were included and divided into five groups according to surgical ages (<2, 2-3, 3-4, 4-5, and 5-6 years). The postoperative myopic shift rates, spherical equivalents (SEs), and the best corrected visual acuity (BCVA) were measured and analyzed. Results: A total of 1,137 refractive measurements from 234 patients were included, with a mean follow-up period of 34 months. The postoperative mean SEs at each follow-up in the five groups were linearly fitted with a mean R2 = 0.93 ± 0.03, which showed a downtrend of SE with age (linear regression). Among patients with a follow-up of 4 years, the mean postoperative myopic shift rate was 0.84, 0.81, 0.68, 0.24, and 0.28 diopters per year (D/y) in the five age groups (from young to old), respectively. The BCVA of those with a surgical age of <2 years at the 4-year visit was 0.26 (LogMAR), and the mean postoperative myopic shift rate was 0.84 D/y. For patients with a surgical age of 2-6 years, a poorer BCVA at the 4-year visit was found in those with higher postoperative myopic shift rates (r = 0.974, p = 0.026, Pearson's correlation test). Conclusion: Performing cataract surgery for patients before 2 years old and decreasing the postoperative myopic shift rates for those with a surgical age of 2-6 years may benefit visual acuity rehabilitation.

Pressure injury risk factors in patients undergoing general anesthesia surgeries.

BACKGROUND: Pressure injuries result from prolonged pressure and lead to tissue damage, infections, extended recovery times, and an economic burden. PURPOSE: To explore risk factors for pressure injuries in patients who underwent surgery under general anesthesia. METHODS: This retrospective study included patients who underwent surgery at a regional educational hospital in southern Taiwan from January 1, 2018, through December 31, 2018. RESULTS: A comprehensive multivariate analysis was used to identify the prominent risk factors for pressure injury among the 11 231 patients enrolled in this study. These risk factors were an age of ≥65 years; surgery duration of >120 minutes; diastolic blood pressure of <60 mm Hg for >30 minutes during surgery; intraoperative use of dopamine, norepinephrine, or epinephrine as vasopressors; American Society of Anesthesiologists physical classification of III or higher; minimum intraoperative body temperature of ≤35°C; blood loss of >500 mL; and a supine or prone surgical position. CONCLUSIONS: This study identified several pressure injury risk factors related to surgical conditions and patient characteristics. Surgical teams must monitor, control, and manage these factors, prioritize staff education, and adopt preventive protocols.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

Risk of Pediatric Bipolar Disorder After General Anesthesia in Infants and Toddlers: A Propensity Score-Matched Population-Based Cohort Study.

BACKGROUND AND HYPOTHESIS: The potential role of anesthesia as an independent risk factor for childhood bipolar disorder (BD) remains unclear. To address this, we conducted a population-based cohort study employing propensity score matching to compare BD incidence between pediatric patients undergoing surgery with and without general anesthesia. STUDY DESIGN: Our study included patients aged 0-3 years who received at least 1 episode of general anesthesia and were hospitalized for over 1 day in Taiwan between January 2004 and December 2014. They were matched 1:1 with a population not receiving general anesthesia to assess pediatric BD incidence. STUDY RESULTS: The study cohort comprised 15 070 patients, equally distributed between the general anesthesia and nongeneral anesthesia groups (7535 each). Multivariate Cox regression analysis revealed adjusted hazard ratios (aHRs; 95% CIs) for pediatric BD in the general anesthesia group as 1.26 (1.04-1.54; P = .021) compared to the nongeneral anesthesia group. Moreover, the incidence rate ratio (95% CI) for the general anesthesia group was 1.26 (1.03-1.53) compared to the nongeneral anesthesia group. CONCLUSIONS: Early childhood exposure to general anesthesia is significantly associated with an increased risk of pediatric BD. This expands understanding of pediatric BD's complex development, informing preventive strategies, and enhancing mental health outcomes for vulnerable young patients and global pediatric healthcare.