Multicenter propensity score-matched analysis to compare perioperative morbidity after laparoscopic or robotic complex hepatectomy for solitary hepatocellular carcinoma.

BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.

Prognostic value of the Naples prognostic score in patients with intrahepatic cholangiocarcinoma after hepatectomy.

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Survival benefit from adjuvant TACE combined with Lenvatinib for patients with hepatocellular carcinoma and microvascular invasion after curative hepatectomy.

BACKGROUND AND AIMS: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy. METHODS: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors. RESULTS: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099-0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129-0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS. CONCLUSION: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy.

Multimodal mechanisms of pathogenic variants in the signal peptide of FIX leading to hemophilia B.

Signal peptide (SP) is essential for protein secretion, and pathogenic variants in the SP of FIX have been identified in hemophilia B (HB). However, the underlying mechanism for the genotype-phenotype correlation of these variants has not been well studied. Here we systematically examined the effects of 13 pathogenic point variants in the SP of FIX using different approaches. Our results showed that these point variants lead to HB by missense variants and/or aberrant pre-mRNA splicing. The missense variants in h-region mainly affected the co-translational translocation function of the SP, and those in c-region caused FIX deficiency mainly by disturbing the co-translational translocation and/or cleavage of the SP. Almost absolute aberrant pre-mRNA splicing was only observed in variants of c.82T>G, but a slight change of splicing patterns was found in variants of c.53G>T, c.77C>A, c.82T>C, and c.83G>A, indicating that these variants might have different degree to affect pre-mRNA splicing. Although two 6-nt deletion aberrant pre-mRNA splicing products caused FIX deficiency by disturbing the SP cleavage, but they could produce some functional mature FIX and vitamin K could increase the secretion of functional FIX. Taken together, our data indicated that pathogenic variants in the SP of FIX caused HB through diverse molecular mechanisms or even a mixture of several mechanisms, and vitamin K availability could be partially attributed to varying bleeding tendencies in patients carrying the same variant in the SP.

Advancing treatment strategies for posterior malleolar malunion: The ankle dislocation method.

BACKGROUND: This study aimed to assess the radiological and clinical outcomes of treatment using the ankle dislocation method for posterior malleolar malunion. METHOD: Thirty-one patients with posterior malleolar malunion who underwent treatment using the ankle dislocation method from May 2015 to October 2021 were retrospectively analyzed. Key outcome measures were radiographic parameters (articular step-off, tibiofibular clear space, fibular length, tibial lateral surface angle, and ankle osteoarthritis), clinical scores (American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and Visual Analogue Scale), and patient satisfaction rate. RESULT: Preoperative computed tomography revealed that Bartoní cek types 3 and 4 accounted for 64.5 % (n = 20) of total cases. Most posterior malleolar malunions were accompanied by depressed intercalary fragments (61.2 % [n = 19]). At the final follow-up, radiographic parameters and clinical scores showed significant improvements postoperatively (P < 0.05), with a high patient satisfaction rate of 77.4 %. Subgroup analysis revealed that the posterior malleolar fracture morphology significantly affected postoperative pain, particularly in more complex fractures (P < 0.001). CONCLUSION: The ankle dislocation method effectively exposes the distal tibial articular surface and facilitates the anatomical restoration of joint congruity under direct vision. This approach substantially improves the clinical and imaging outcomes in patients with complex posterior malleolar malunion. LEVELS OF EVIDENCE: Level IV, retrospective case series.

Expression and significance of pin1 in the wound healing.

The aim of this study is to delineate the expression patterns of prolyl cis-trans isomerase NIMA-interacting protein 1 (Pin1), Glial cell-derived neurotrophic factor (GDNF), and Angiotensin II (ANG II) during the process of wound repair, and to ascertain the effects of Pin1, GDNF, and ANG II on the healing of wounds in a rat model. A total of 18 rats were allocated into three groups-sham (control), DMSO (vehicle control), and Pin1 inhibitor (treatment with juglone)-with six animals in each group. An animal model of wound healing was established, followed by the intraperitoneal administration of juglone. Tissue samples from the wounds were subsequently collected for histopathological evaluation. Expression levels of Pin1, GDNF, and Ang II were quantified. In addition, an in vitro model of wound healing was created using human umbilical vein endothelial cells (HUVEC), to assess cell proliferation, migration, and tube formation under conditions of juglone pre-treatment. The expression levels of Pin1, GDNF, and ANG II were notably elevated on 7-, and 10- days post-wound compared to those measured on 3-day. Contrastingly, pre-treatment with juglone significantly inhibited the expression of these molecules. Histological analyses, including HE (Hematoxylin and Eosin), Masson's trichrome, and EVG (Elastic van Gieson) staining, demonstrated that vascular angiogenesis, as well as collagen and elastin deposition, were substantially reduced in the juglone pre-treated group when compared to the normal group. Further, immunohistochemical analysis revealed a considerable decrease in CD31 expression in the juglone pre-treatment group relative to the normal control group. Pin1 serves as a pivotal facilitator of wound repair. The findings indicate that the modulation of Pin1, GDNF, and ANG II expression impacts the wound healing process in rats, suggesting potential targets for therapeutic intervention in human wound repair.

FOXP4-AS1 promotes CD8+ T cell exhaustion and esophageal cancer immune escape through USP10-stabilized PD-L1.

Esophageal cancer (EC) is the 9th most frequently diagnosed malignancy globally with unfavorable prognosis. Immune escape is one of the principal factors leading to poor survival, however, the mechanism underlying immune escape remains largely uninvestigated. The xenograft mouse model and EC cell-CD8+ cytotoxic T lymphocytes (CTLs) co-culture system were established. Immunohistochemistry, qRT-PCR or western blot were employed to detect the levels of long non-coding RNA (lncRNA) FOXP4-AS1, PD-L1, USP10 and other molecules. The abundance of T cells, cytokine production and cell apoptosis were monitored by flow cytometry. The viability of CTLs was assessed by Trypan blue staining. The binding between FOXP4-AS1 and USP10 was validated by RNA pull-down assay, and the interaction between USP10 and PD-L1, as well as the ubiquitination of PD-L1, were detected by co-immunoprecipitation. The elevation of FOXP4-AS1 in EC was associated with decreased CTL abundance, and upregulated PD-L1 facilitated CTL apoptosis in EC. FOXP4-AS1 accelerated EC tumor growth by decreasing the abundance of tumor infiltrating CTLs in vivo. FOXP4-AS1 inhibited the viability of CTLs and facilitated the cytotoxicity and exhaustion of CTLs. In Kyse 450 cell-CTL co-culture system, FOXP4-AS1 suppressed the viability and abundance of CTLs, and inhibited EC cell apoptosis via PD-L1. Mechanistically, FOXP4-AS1 regulated the ubiquitination of PD-L1 through deubiquitinating enzyme USP10. FOXP4-AS1 promoted CTL exhaustion and EC immune escape through USP10-stabilized PD-L1. HIGHLIGHTS: PD-L1 facilitated CD8+ T cell apoptosis in EC. Upregulated FOXP4-AS1 promoted EC tumor growth by inhibiting the viability and facilitating the cytotoxicity and exhaustion of tumor infiltrating CD8+ T cells. FOXP4-AS1 suppressed the viability and abundance of CD8+ T cells through USP10-mediated deubiquitination of PD-L1.

Effect of early peri-operative arterial lactate concentration level ratios on post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. METHODS: The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF. RESULTS: A total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097-9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792). CONCLUSIONS: Early assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis.

Decreased structural pathways mediating functional connectivity in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep breathing disorder that is often accompanied by changes in structural connectivity (SC) and functional connectivity (FC). However, the current understanding of the interaction between SC and FC in OSA is still limited. METHODS: The aim of this study is to integrate complementary neuroimaging modalities into a unified framework using multi-layer network analysis methods and to reveal their complex interrelationships. We introduce a new graph metric called SC-FC bandwidth, which measures the throughput of SC mediating FC in a multi-layer network. The bandwidth differences between two groups are evaluated using the network-based statistics (NBS) method. Additionally, we traced and analyzed the SC pathways corresponding to the abnormal bandwidth. RESULTS: In both the healthy control and patients with OSA, the majority offunctionally synchronized nodes were connected via SC paths of length 2. With the NBS method, we observed significantly lower bandwidth between the right Posterior cingulate gyrus and right Cuneus, bilateral Middle frontal gyrus, bilateral Gyrus rectus in OSA patients. By tracing the high-proportion SC pathways, it was found that OSA patients typically exhibit a decrease in direct SC-FC, SC-FC triangles, and SC-FC quads intra- and inter-networks. CONCLUSION: Complex interrelationship changes have been observed between the SC and FC in patients with OSA, which might leads to abnormal information transmission and communication in the brain network.

N-alkylamides from Litsea cubeba (Lour.) Pers. with potential anti-inflammatory activity.

Six amides, including a new N-alkylamide (1), four known N-alkylamides (2-5) and one nicotinamide (6) were isolated from Litsea cubeba (Lour.) Pers., which is a pioneer herb traditionally utilized in medicine. Their structures were elucidated on the basis of 1D and 2D NMR experiments and by comparison of their spectroscopic and physical data with the literature values. Cubebamide (1) is a new cinnamoyltyraminealkylamide and possessed obvious anti-inflammatory activity against NO production with IC50 values of 18.45 µM. Further in-depth pharmacophore-based virtual screening and molecular docking were carried out to reveal the binding mode of the active compound inside the 5-LOX enzyme. The results indicate that L. cubeba, and the isolated amides might be useful in the development of lead compounds for the prevention of inflammatory diseases.

The Reduced Gray Matter Volume and Functional Connectivity of the Cerebellum in Type 2 Diabetes Mellitus with High Insulin Resistance.

INTRODUCTION: Insulin resistance is widely thought to be a critical feature in type 2 diabetes mellitus (T2DM), and there is significant evidence indicating a higher abundance of insulin receptors in the human cerebellum than cerebrum. However, the specific structural or functional changes in the cerebellum related to T2DM remain unclear, and the association between cerebellar alterations, insulin resistance, cognition, and emotion is yet to be determined. METHODS: We investigated neuropsychological performance, and structural and functional changes in specific cerebellar subregions in 43 T2DM patients with high insulin resistance (T2DM-highIR), 72 T2DM patients with low insulin resistance (T2DM-lowIR), and 50 controls. Furthermore, the correlation and stepwise multiple linear regression analysis were performed. RESULTS: Compared to the controls, T2DM exhibited lower cognitive scores and higher depressive/anxious scores. Furthermore, T2DM-highIR patients showed reduced gray matter volume (GMV) in the right cerebellar lobules VIIb, Crus I/II, and T2DM showed reduced GMV in left lobules I-IV compared to controls. Additionally, functional connectivity decrease was observed between the right lobules I-V and orbital part of the superior frontal gyrus in T2DM-highIR compared to both T2DM-lowIR and controls. Notably, there were negative correlations between the GMV of the lobules VIIb, Crus I/II, and updated homeostatic model assessment of insulin resistance, and positive correlation with executive/visuospatial performance in T2DM patients. CONCLUSIONS: These results suggest that the cerebellar lobules VIIb, Crus I/II, represent vulnerable brain regions in the context of insulin resistance. Overall, this study offers new insights into the neuropathophysiological mechanisms of brain impairment in patients with T2DM.

Intracranial mesenchymal tumor with multiple extracranial metastases: A case report and literature review.

This study presents a rare case of an older woman with an intracranial mesenchymal tumor in the right frontal and parietal lobes. Despite prompt surgical intervention, her condition rapidly deteriorated because of tumor dissemination, leading to her demise. We highlight the tumor's marked invasiveness and heterogeneity, coupled with a propensity for distant systemic metastasis, which negatively impacted the patient's prognosis. This particular clinical behavior had not been previously reported, making this a novel observation. Thus, through a comprehensive review of relevant literature, we aim to provide valuable insights for further understanding, diagnosing, and treating such tumors.

[In vitro biological evaluation of PEGylated poly(glycerol sebacate)/ß-TCP-coating modified magnesium alloy].

PURPOSE: To prepare PEGS/ß-TCP modified magnesium alloy (PEGS/ß-TCP/MZG) membranes by forming a glycolated poly(sebacate)/ß-tricalcium phosphate (PEGS/ß-TCP) coating on the surface of magnesium-zinc-gadolinium alloy (MZG) membranes, and to evaluate the osteogenic induction activity and immunomodulatory properties of PEGS/ß-TCP/MZG using the material extract medium. METHODS: PEGS/ß-TCP coating was prepared on the surface of MZG by solvent method, and the PEGS/ß-TCP/MZG membrane was fabricated and compared with PEGS/ß-TCP and MZG to examine the morphology, composition, and hydrophilicity. The amount of magnesium ions released and the pH value of the materials were tested after 3 days of immersion. The cell viability and osteogenic differentiation of MC3T3 cells induced by extract medium were investigated by CCK-8 assay, ALP and mineralized nodule staining. The cell viability and polarization of RAW cells induced by extract medium were then investigated. The expression of macrophage-secreted cytokines was examined by PCR analysis. GraphPad Prism 9.0 software package was used for statistical analysis. RESULTS: PEGS/ß-TCP/MZG membranes with PEGS/ß-TCP coating tightly embedded with MZG were successfully fabricated, and the material had good hydrophilicity. The results of degradation experiments indicated that the PEGS/ß-TCP coating effectively slowed down the degradation rate of MZG, leading to a lower pH value and concentration of Mg2+ ion in the extract medium of PEGS/ß-TCP/MZG group. The results of in vitro cell experiments showed that PEGS/ß-TCP/MZG had no significant effect on the proliferation activity of both MC3T3-E1 and macrophages. PEGS/ß-TCP/MZG significantly enhanced the expression of ALP and mineralized nodule staining in MC3T3-E1. Although there was no significant difference in macrophage polarization pattern between PEGS/ß-TCP and PEGS/ß-TCP/MZG groups, PEGS/ß-TCP/MZG further reduced inflammation based on the immunomodulation of PEGS/ß-TCP coating related TNF-α expression and increased osteogenesis related TGF-ß expression. CONCLUSIONS: MZG membrane modified by PEGS/ß-TCP may provide a new material option for the development of bone tissue engineering.

High SNHG expression may predict a poor lung cancer prognosis based on a meta-analysis.

BACKGROUND: An increasing number of small nucleolar RNA host genes (SNHGs) have been revealed to be dysregulated in lung cancer tissues, and abnormal expression of SNHGs is significantly correlated with the prognosis of lung cancer. The purpose of this study was to conduct a meta-analysis to explore the correlation between the expression level of SNHGs and the prognosis of lung cancer. METHODS: A comprehensive search of six related databases was conducted to obtain relevant literature. Relevant information, such as overall survival (OS), progression-free survival (PFS), TNM stage, lymph node metastasis (LNM), and tumor size, was extracted. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to evaluate the relationship between SNHG expression and the survival outcome of lung cancers. Sensitivity and publication bias analyses were performed to explore the stability and reliability of the overall results. RESULTS: Forty publications involving 2205 lung cancer patients were included in this meta-analysis. The pooled HR and 95% CI values indicated a significant positive association between high SNHG expression and poor OS (HR: 1.890, 95% CI: 1.595-2.185), disease-free survival (DFS) (HR: 2.31, 95% CI: 1.57-3.39) and progression-free survival (PFS) (HR: 2.01, 95% CI: 0.66-6.07). The pooled odds ratio (OR) and 95% CI values indicated that increased SNHG expression may be correlated with advanced TNM stage (OR: 1.509, 95% CI: 1.267-1.799), increase risk of distant lymph node metastasis (OR: 1.540, 95% CI: 1.298-1.828), and large tumor size (OR: 1.509, 95% CI: 1.245-1.829). Sensitivity analysis and publication bias results showed that each result had strong reliability and robustness, and there was no significant publication bias or other bias. CONCLUSION: Most SNHGs are upregulated in lung cancer tissues, and high expression of SNHGs predicts poor survival outcomes in lung cancer. SNHGs may be potential prognostic markers and promising therapeutic targets.

Prognostic value of platelet distribution width to lymphocyte ratio in patients with hepatocellular carcinoma following hepatectomy.

BACKGROUND: Platelet distribution width (PDW), but not platelet count, was found to more comprehensively reflect platelet activity. The present study, thus, aimed to evaluate the prognostic value of PDW to lymphocyte ratio (PDWLR) in patients with hepatocellular carcinoma (HCC) following hepatectomy. METHODS: Patients following hepatectomy were analyzed retrospectively. The Kaplan-Meier survival curves and Cox regression model were used to determine the prognostic value of PDWLR. RESULTS: 241 patients were analyzed eventually, and stratified into low and high PDWLR groups (≤ 9.66 vs. > 9.66). Results of comparing the baseline characteristics showed that high PDWLR was significantly associated with cirrhosis, and intraoperative blood loss (all P < 0.05). In multivariate COX regression analysis, PDWLR was demonstrated as an independent risk factor for OS (HR: 1.549, P = 0.041) and RFS (HR: 1.655, P = 0.005). Moreover, PDWLR demonstrated a superior capacity for predicting prognosis compared to other indicators. CONCLUSION: Preoperative PDWLR has a potential value in predicting the prognosis of HCC patients following hepatectomy, which may help in clinical decision-making for individual treatment.

Identification of a Prognostic Gene Signature Based on Lipid Metabolism-Related Genes in Esophageal Squamous Cell Carcinoma.

Background: Dysregulation of lipid metabolism is common in cancer. However, the molecular mechanism underlying lipid metabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are not well understood. The objective of our study was to construct a lipid metabolism-related prognostic model to improve prognosis prediction in ESCC. Methods: We downloaded the mRNA expression profiles and corresponding survival data of patients with ESCC from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We performed differential expression analysis to identify differentially expressed lipid metabolism-related genes (DELMGs). We used Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to establish a risk model in the GEO cohort and used data of patients with ESCC from the TCGA cohort for validation. We also explored the relationship between the risk model and the immune microenvironment via infiltrated immune cells and immune checkpoints. Results: The result showed that 132 unique DELMGs distinguished patients with ESCC from the controls. We identified four genes (ACAA1, ACOT11, B4GALNT1, and DDHD1) as prognostic gene expression signatures to construct a risk model. Patients were classified into high- and low-risk groups as per the signature-based risk score. We used the receiver operating characteristic (ROC) curve and the Kaplan-Meier (KM) survival analysis to validate the predictive performance of the 4-gene signature in both the training and validation sets. Infiltrated immune cells and immune checkpoints indicated a difference in the immune status between the two risk groups. Conclusion: The results of our study indicated that a prognostic model based on the 4-gene signature related to lipid metabolism was useful for the prediction of prognosis in patients with ESCC.

[Prescription and medication rules of traditional Chinese medicine for prevention and treatment of diabetic microangiopathy based on literature mining].

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.

Asymmetric Construction of Multifunctional γ-Lactams from 1,3-Dienes and α-Ketoamides via Pd(0)-π-Lewis Base Catalysis.

A straightforward approach for the asymmetric synthesis of multifunctionalized γ-lactams, including those bearing two tetrasubstituted stereogenic centers, has been developed through a palladium-catalyzed vinylogous addition/allylic amination process between 1,3-dienes and α-ketoamides. This protocol features advantages of ready substrate availability, broad applicability, high efficiency, and excellent stereoselectivity, making it an attractive complementary tool to the previous strategies.

Brain morphology and functional connectivity alterations in patients with severe obstructive sleep apnea.

BACKGROUND: It has been demonstrated that widespread structural and functional brain alterations influence the development of cognitive impairment in patients with obstructive sleep apnea (OSA). However, the literature has limited evidence regarding the neuropathophysiological mechanisms behind these impairments. This research aimed to investigate brain morphologic and functional connectivity (FC) abnormalities related to neurocognitive function in OSA. METHODS: Fifty treatment-naïve males, newly diagnosed patients with severe OSA, and 50 well-matched healthy controls (HCs) were enrolled prospectively. All subjects underwent an MRI scan, cognitive psychological and sleep scale assessment. The differences of brain morphological and seed-based FC between the two groups were compared. The correlation analysis and receiver operating characteristic curve were performed for further analysis. RESULTS: Compared with HCs, the right brainstem, left dorsal-lateral superior frontal gyrus (SFGdor), and superior temporal gyrus (STG) exhibited atrophy in the OSA group. In addition, FC between the left SFGdor and the right postcentral gyrus (PoCG) was increased, which was positively correlated with disease duration (r = 0.312, FDR-corrected P = 0.027). The Jacobian values of the brainstem were negatively correlated with MoCA and recall scores (r = -0.449, FDR-corrected P = 0.0025; r = -0.416, FDR-corrected P = 0.005). Furthermore, the Jacobian values of the left SFGdor demonstrated a relatively high diagnostic performance (sensitivity: 86%, specificity: 56%, AUC: 0.740, 95% CI: 0.643-0.836, P < 0.0001). CONCLUSIONS: Structural atrophy in brainstem and frontotemporal lobe and altered FC may be the neurobiological hallmark of brain impairment in OSA. Notably, brainstem atrophy has been associated with cognitive impairment, which may provide new insights into understanding the neuropathophysiological mechanisms of cognitive impairment in OSA patients.

Effect on Satisfactory Seizure Control and Heart Rate Variability of Thread-Embedding Acupuncture for Drug-Resistant Epilepsy: A Patient-Assessor Blinded, Randomized Controlled Trial.

This randomized controlled trial investigates the efficacy of thread-embedding acupuncture (TEA) compared to sham TEA in treating drug-resistant epilepsy (DRE). Fifty-four DRE outpatients were randomly divided into two groups: TEA (27 patients) and sham TEA (27 patients). Both groups received four sessions of TEA or sham TEA, spaced four weeks apart, targeting GV20, GV14, BL15, BL18, ST40, and GB34 acupoints. Antiseizure medications were maintained at consistent doses throughout the study. Outcome measures included satisfactory seizure control, seizure freedom, and heart rate (HR) and heart rate variability (HRV) measurements. TEA demonstrated a significantly higher rate of satisfactory seizure control at follow-up compared to the sham TEA group (37% vs. 3.7%, p = 0.003). While no significant intergroup differences were observed in HR, HRV, and HRV components at each stage, the TEA group experienced a significant decrease in HR and a significant increase in HRV posttreatment. This study demonstrates TEA's effectiveness in managing DRE and suggests its impact may relate to heightened parasympathetic nerve activity. Further research with extended follow-up periods is necessary to validate these findings.