Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation / 亚洲男科学杂志(英文版)

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.

Comparison of cytokine levels in prostatic secretion between the IIIa and IIIb subtypes of prostatitis / 亚洲男科学杂志(英文版)

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), also known as National Institutes of Health (NIH) type III prostatitis, is a common disorder with an unclear etiology and no known curative treatments. Based on the presence or absence of leukocytes in expressed prostatic secretion (EPS), CP/CPPS is classified further into IIIa (inflammatory) and IIIb (noninflammatory) subtypes. However, the severity of symptoms is not entirely consistent with the white blood cell (WBC) count. Following the preliminary finding of a link between inflammatory cytokines and CP/CPPS, we performed this clinical study with the aim of identifying cytokines that are differentially expressed according to whether the prostatitis subtype is IIIa or IIIb. We found that granulocyte colony-stimulating factor (G-CSF), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) levels were significantly elevated and interferon-inducible protein-10 (IP-10) and platelet-derived growth factor-BB (PDGF-BB) levels were downregulated in the EPS of patients with type IIIa prostatitis. In a word, it is a meaningful study in which we investigate the levels of various cytokines in EPS according to whether prostatitis is the IIIa or IIIb subtype. The combination of G-CSF, IL-18, MCP-1, IP-10, and PDGF-BB expression levels could form a basis for classification, diagnosis, and therapeutic targets in clinical CP/CPPS.

Factors influencing the sperm retrieval rate of microdissection testicular sperm extraction in patients with nonmosaic Klinefelter syndrome / 亚洲男科学杂志(英文版)

To investigate the factors affecting the sperm retrieval rate of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS), 64 patients with nonmosaic KS who underwent micro-TESE in the Center for Reproductive Medicine of Peking University Third Hospital (Beijing, China) between January 2016 and December 2017 were included in the study. Data on medical history, physical examination and laboratory examination results, and micro-TESE outcomes were collected. Patients were divided into two groups according to micro-TESE outcomes. The following factors were compared between the two groups by the Mann‒Whitney U test or Student's t-test based on the distribution (nonnormal or normal) of the factors: age, testicular size, follicle-stimulating hormone level, luteinizing hormone level, testosterone level, and anti-Müllerian hormone level. The overall success rate of sperm retrieval was 50.0%. Correlation analysis showed that testicular volume was positively correlated with testosterone level. Using a logistic regression model, age and anti-Müllerian hormone levels were found to be better predictors for the sperm retrieval rate than the other parameters.

Knot-free anchor repair of anterior talofibular ligament under total ankle arthroscopy / 中国骨伤

OBJECTIVE@#To explore clinical effect of repairing anterior talofibular ligament with knot-free anchors under total ankle arthroscopy in treating chronic lateral ankle instability.@*METHODS@#From April 2018 to August 2021, 24 patients with chronic lateral ankle instability were treated with knot-free anchors under total ankle arthroscopy to repair anterior talofibular ligament, including 16 males and 8 females, aged from 22 to 42 years old with an average of(28.6±5.8) years old;the time from injury to opertaion ranged from 6 to 10 months with an average of(7.7±1.3) months. Preoperative and postoperative American Orhopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS), talar tilt, anterior talar translation(ATT) were recorded and compared.@*RESULTS@#All patients were followed up from 10 to 12 months with an average of (10.2±1.14) months. Incision were healed at stageⅠ, and no infection, nerve injury and lateral ankle instability occurred. AOFAS score improved from(52.79±8.96) before opertaion to (93.00± 4.01) at 6 months after operation, 23 patients got excellent result and 1 good;VAS decreased from (5.50±0.98) before opertaion to (1.04±0.80) at 6 months after operation(P<0.05);talar tilt decreased from(9.16±2.09)° to (3.10±1.72)° at 3 months after operation(P<0.05);ATT decreased from(8.80±2.55) mm to (2.98±1.97) mm at 3 months after operation(P<0.05). Twenty-four patients drawer test and varus-valgus rotation wer negative.@*CONCLUSION@#Repairing anterior talofibular ligament with knot-free anchors under total ankle arthroscopy for the treatment of chronic lateral ankle instability has advantages of less trauma, less complications safe and reliable, and good recovery of ankle joint function.

Resveratrol Prevents Vibrio vulnificus-Induced Sepsis by Attenuating Necroptosis / 生物医学与环境科学（英文）

OBJECTIVE@#This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol (RSV) regulate necroptosis during Vibrio vulnificus (V. vulnificus)-induced sepsis and the potential mechanism.@*METHODS@#The effect of RSV on V. vulnificus cytolysin (VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V. vulnificus-induced sepsis mouse model.@*RESULTS@#RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells. RSV also inhibited the inflammatory response, had a protective effect on histopathological changes, and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages, lung, spleen, and liver tissues of V. vulnificus-induced septic mice in vivo. Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V. vulnificus-induced septic mice. RSV also improved the survival of V. vulnificus-induced septic mice.@*CONCLUSION@#Our findings collectively demonstrate that RSV prevented V. vulnificus-induced sepsis by attenuating necroptosis, highlighting its potency in the clinical management of V. vulnificus-induced sepsis.

Validation of Pharyngeal Acid Reflux Episodes Using Hypopharyngeal Multichannel Intraluminal Impedance-pH

Background/Aims@#Hypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility. @*Methods@#We conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed. @*Results@#A total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%. @*Conclusion@#Our preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

Tissue Quality Comparison Between Heparinized Wet Suction and Dry Suction in Endoscopic Ultrasound-Fine Needle Biopsy of Solid Pancreatic Masses: A Randomized Crossover Study

Background/Aims@#A high-quality sample allows for next-generation sequencing and the administration of more tailored precision medicine treatments. We aimed to evaluate whether heparinized wet suction can obtain higher quality samples than the standard dry-suction method during endoscopic ultrasound (EUS)-guided biopsy of pancreatic masses. @*Methods@#A prospective randomized crossover study was conducted. Patients with a solid pancreatic mass were randomly allocated to receive either heparinized wet suction first or dry suction first. For each method, two needle passes were made, followed by a switch to the other method for a total of four needle punctures. The primary outcome was the aggregated white tissue length. Histological blood contamination, diagnostic performance and adverse events were analyzed as secondary outcomes. In addition, the correlation between white tissue length and the extracted DNA amount was analyzed. @*Results@#A total of 50 patients were enrolled, and 200 specimens were acquired (100 with heparinized wet suction and 100 with dry suction), with one minor bleeding event. The heparinized wet suction approach yielded specimens with longer aggregated white tissue length (11.07 mm vs 7.96 mm, p=0.001) and less blood contamination (p=0.008). A trend towards decreasing tissue quality was observed for the 2nd pass of the dry-suction method, leading to decreased diagnostic sensitivity and accuracy, although the accumulated diagnostic performance was comparable between the two suction methods. The amount of extracted DNA correlated positively to the white tissue length (p=0.001, Spearman ̕s ρ=0.568). @*Conclusions@#Heparinized wet suction for EUS tissue acquisition of solid pancreatic masses can yield longer, bloodless, DNA-rich tissue without increasing the incidence of adverse events (ClinicalTrials.gov. identifier NCT04707560).

Distal Mean Nocturnal Baseline Impedance Predicts Pathological Reflux of Isolated Laryngopharyngeal Reflux Symptoms

Background/Aims@#Diagnosis of isolated laryngopharyngeal reflux symptoms (ILPRS), ie, without concomitant typical reflux symptoms (CTRS), remains difficult. Mean nocturnal baseline impedance (MNBI) reflects impaired mucosal integrity. We determined whether esophageal MNBI could predict pathological esophagopharyngeal reflux (pH+) in patients with ILPRS. @*Methods@#In this cross-sectional study conducted in Taiwan, non-erosive or low-grade esophagitis patients with predominant laryngopharyngeal reflux symptoms underwent combined hypopharyngeal multichannel intraluminal impedance-pH monitoring when off acid suppressants. Participants were divided into the ILPRS (n = 94) and CTRS (n = 63) groups. Asymptomatic subjects without esophagitis (n = 25) served as healthy controls. The MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES) and the proximal esophagus were measured. @*Results@#Distal but not proximal esophageal median MNBI values were significantly lower in patients with pH+ than in those with pH– (ILPRS in pH+ vs pH–: 1607 Ω vs 2709 Ω and 1885 Ω vs 2563 Ω at 3 cm and 5 cm above LES, respectively; CTRS in pH+ vs pH–: 1476 vs 2307 Ω and 1500 vs 2301 Ω at 3 cm and 5 cm above LES, respectively, P < 0.05 for all). No significant differences of any MNBI exist between any pH– subgroups and healthy controls. The areas under the receiver operating characteristic curve in the ILPRS group were 0.75 and 0.80, compared to the pH– subgroup and healthy controls (P < 0.001 for both), respectively. Interobserver reproducibility was good (Spearman correlation 0.93, P < 0.0001). @*Conclusion@#Distal esophageal MNBI predicts pathological reflux in patients with ILPRS.

Individualized Concurrent Chemotherapy for Patients with Stage III-IVa Nasopharyngeal Carcinoma Receiving Neoadjuvant Chemotherapy Combined with Definitive Intensity-Modulated Radiotherapy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This retrospective study aimed to re-evaluate the effect of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). @*Materials and Methods@#A total of 498 patients who received neoadjuvant chemotherapy (NCT) combined with concurrent chemoradiotherapy (CCRT) or IMRT were retrospectively reviewed. The distribution of baseline characteristics was balanced using propensity score matching. Additionally, the results of NCT+IMRT and NCT+CCRT were compared using Kaplan-Meier survival analysis, and differences in survival rates were analyzed using the log rank test. @*Results@#There were no significant differences in overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LRFS) between the two groups. Patients were further categorized into risk subgroups based on pretreatment Epstein-Barr virus (EBV) DNA cutoff values using receiver operating characteristic curve analysis. There were no statistically significant differences in OS, PFS, DMFS, and LRFS between patients who received NCT+CCRT and NCT+IMRT in the high-risk group. In the low-risk group, although there were no differences between NCT+CCRT and NCT+IMRT in OS, PFS, and LRFS, patients who received NCT+CCRT had better DMFS than those who received NCT+IMRT. @*Conclusion@#Pretreatment EBV DNA level can be used to individualize concurrent chemotherapy for patients with locally advanced NPC. Patients with low pretreatment EBV DNA levels may benefit from concurrent chemotherapy, whereas those with high levels may not. Other treatment modalities need to be explored for high-risk patients to improve their prognosis.

Bioactive neolignans and lignans from the roots of Paeonia lactiflora / 中国天然药物

Two new neolignans and one new lignan (1-3) were obtained from the roots of Paeonia lactiflora. Their structures were unambiguously elucidated based on extensive spectroscopic analysis, single-crystal X-ray crystallography, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 was a racemic mixture and successfully resolved into the anticipated enantiomers via chiral-phase HPLC. Compound 3 demonstrated moderate inhibitory activity against human carboxylesterase 2A1 (hCES2A1) with an IC50 value of 7.28 ± 0.94 μmol·-1.

Three new ursane-type triterpenoids from Rosmarinus officinalis and their biological activities / 中国天然药物

Three new ursane-type triterpenoids, 3-oxours-12-en-20, 28-olide (1), 3β-hydroxyurs-12-en-20, 28-olide (2) and 3β-hydroxyurs-11, 13(18)-dien-20, 28-olide (3), were isolated from a potent anti-inflammatory and antibacterial fraction of the ethanolic extract of Rosmarinus officinalis. Their structures were elucidated by a combination of extensive 1D- and 2D-NMR experiments, MS data and comparisons with literature reports. Compounds 1-3 exhibited significantly inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages, but no antibacterial activity was found at a concentration of 128 μg·mL-1.

Risk assessment of internal mammary lymph node metastasis and choice of irradiation of internal mammary lymphatic drainage area in breast cancer patients with negative internal breast lymph nodes on imaging / 中华肿瘤杂志

Objective: To explore the independent risk factors of internal mammary lymph nodes (IMN) metastasis and the risk assessment method of IMN metastasis preoperatively in breast cancer patients with negative IMN in imaging examination, and guide the radiotherapy of IMN in patients with different risk stratification of IMN metastasis. Methods: The clinical and pathological data of 301 breast cancer patients who underwent internal mammary sentinel node biopsy(IM-SLNB) and/or IMN dissection in Shandong Cancer Hospital with negative IMN on CT and/or MRI from January 2010 to October 2019 were analyzed retrospectively. The independent risk factors were analyzed by univariate and multivariate logistic regression, and the independent risk factors of IMN metastasis were used to risk stratification. Results: Among the 301 patients, 43 patients had IMN metastasis, and the rate of IMN metastasis was 14.3%. Univariate analysis showed that vascular tumor thrombus, progesterone receptor (PR) expression, T stage and N stage were associated with IMN metastasis. Multivariate logistic regression analysis showed that tumor located in medial quadrant, positive PR and axillary lymph node metastasis were independent risk factors for IMN metastasis. The risk of IMN metastasis was assessed according to the independent risk factors of the patients: low-risk group is including 0 risk factor, medium-risk group is including 1 risk factor, and high-risk group is including 2-3 risk factors. According to this evaluation criteria, 301 patients with breast cancer were divided into low-risk group (with 0 risk factors), medium-risk group (with 1 risk factor) and high-risk group (with 2-3 risk factors). The IMN metastasis rates were 0 (0/34), 4.3% (6/140) and 29.1% (37/127), respectively. Conclusions: The risk stratification of IMN metastasis according to three independent risk factors of IMN metastasis including tumor located in medial quadrant, positive PR and axillary lymph node metastasis in breast cancer patients can guide the radiotherapy of IMN in newly diagnosed breast cancer patients. For N1 patients, radiotherapy of IMN is strongly recommended when the primary tumor is located in the medial quadrant and/or PR positive.

Icariin Inhibits Proliferation of CLC5 Hepatoma Cells via Akt/GSK3β/CDK Pathway / 中国实验方剂学杂志

ObjectiveTo study the effect of icariin on the proliferative capacity of hepatocellular carcinoma cell line CLC5 and the underlying mechanism. MethodThe targets of icariin were screened out by network pharmacology， and the target network and protein-protein interaction （PPI） network were constructed to predict the possible targets and pathways of icariin. CCK-8 assay was employed to explore the effects of different concentrations （0， 6.25， 12.5， 25， 50 μmol·L-1） of icariin on the viability of CLC5 cells. Further， CLC5 cells were treated with 0， 25， 50 μmol·L-1 icariin， and the effect of icariin on CLC5 cell proliferation was examined by Edu-488 assay and clone formation assay （CFA）. Western blot was employed to measure the expression levels of proteins in the protein kinase B （Akt）/glycogen synthase kinase 3β （GSK3β）/cell cycle-dependent kinase （CDK） pathway in the CLC5 cells exposed to different concentrations of icariin. ResultNetwork pharmacological analysis revealed that icariin may inhibit the hepatocellular carcinoma via cell cycle arrest and inhibition of tumor cell proliferation. Compared with the blank group， icariin decreased the viability of CLC5 cells in a time- and concentration-dependent manner （P<0.01） and reduced the positive rate of Edu-488 and the colonies in CFA （P<0.05， P<0.01）. Moreover， icariin down-regulated the protein levels of p-Akt， p-GSK3β， CDK4， and CyclinD1 （P<0.05， P<0.01）. ConclusionIcariin may block cell cycle to suppress the proliferation of CLC5 cells via inhibiting the Akt/GSK3β/CDK pathway.

Risk factors for bone cement leakage and recompression of injured vertebrae after percutaneous kyphoplasty for osteoporotic vertebral compression fracture / 中华创伤杂志

Objective:To investigate the risk factors of bone cement leakage and recompression of injured vertebrae after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF).Methods:A case-control study was performed to analyze the clinical data of 297 patients with single-segment OVCF who underwent PKP in First Affiliated Hospital of Soochow University from January 2017 to January 2021, including 67 males and 230 females; aged 60-92 years [(69.5±8.2)years]. According to the occurrence of bone cement leakage, the patients were divided into leakage group ( n=36) and no leakage group ( n=261). According to the occurrence of recompression of injured vertebrae, the patients were divided into recollapse group ( n=40) and no recollapse group ( n=257). The gender, age, fracture segment, type of fracture, fracture severity, cortical disruption, intravertebral cleft, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, bone cement injection volume, bone cement distribution, and postoperative anti-osteoporosis treatment were recorded. Univariate analysis was used to analyze the correlation of those factors with bone cement leakage and recompression of injured vertebrae after PKP, followed by multivariate Logistic regression analysis to identify the independent risk factors. Results:Univariate analysis showed that fracture severity, cortical disruption and bone cement injection volume were related to bone cement leakage ( P<0.05 or 0.01). Gender, age, fracture segment, type of fracture, intravertebral cleft, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, bone cement distribution, and postoperative anti-osteoporosis treatment were not related to bone cement leakage (all P>0.05). Univariate analysis showed that intravertebral cleft, bone cement distribution, and postoperative anti-osteoporosis treatment were associated with recompression of injured vertebrae (all P<0.01). Gender, age, fracture segment, type of fracture, fracture severity, cortical disruption, preoperative and postoperative local kyphosis angle, correction value of local kyphosis angle, and bone cement injection volume were not related to recompression of injured vertebrae (all P>0.05). Multivariate Logistic regression analysis showed that severe fracture ( OR=4.23, 95% CI 1.52-11.81, P<0.01), cortical disruption ( OR=3.29,95% CI 1.52-7.13, P<0.01), and bone cement injection volume >8 ml ( OR=2.31,95% CI 1.09-4.92, P<0.05) were significantly related to bone cement leakage. Multivariate Logistic regression analysis showed that intravertebral cleft ( OR=2.10, 95% CI 1.03-4.30, P<0.05), solid type of bone cement distribution ( OR=2.56, 95% CI 1.25-5.27, P<0.05) and no anti-osteoporosis treatment after operation ( OR=3.06, 95% CI 1.46-6.40, P<0.01) were significantly related to recompression of injured vertebrae. Conclusions:For OVCF patients, severe fracture, cortical disruption, and bone cement injection volume>8 ml are independent risk factors for bone cement leakage after PKP. Intravertebral cleft, solid type of bone cement distribution, and no anti-osteoporosis treatment after operation are independent risk factors for recompression of injured vertebrae after PKP.

Research progress of endoplasmic reticulum stress in methamphetamine induced neurotoxicity / 中国药理学通报

At present, METH has surpassed the traditional illegal psychoactive substances and become the most widely abused illegal psychostimulant in China.Endoplasmic reticulum ( ER) plays an important role in regulating the normal physiological functions of various cells by virtue of its strong membrane strnc- ture and a large number of enzymes on the membrane.Endoplasmic reticulum stress ( ERS) is a series of adaptive responses made by cells when ER homeostasis is destroyed.When ERS occurs, it will drive the activation of unfolded protein response (I PR ) , which aims to protect cells from stress, reduce biosyn- thetic load and help to rebuild cell homeostasis.Persistent ERS will further aggravate the pressure of ER and induce cell death by using UPR signaling pathway.'Hie neurotoxicity induced by METH is closely related to ERS.This paper elaborates on ERS and UPR signaling pathway, and summarizes the relationship between ERS.apoptosis and autophagy, so as to provide new ideas and potential therapeutic targets for the basic research and prevention of METH induced neurotoxicity mechanism.

Research progress on hypoxia-induced imbalance of calcium homeostasis in pulmonary artery smooth muscle cells and its treatment / 中国药理学通报

Chronic hypoxic lung diseases are major causes of disability and mortality worldwide, which are typically aggravated by hypoxic pulmonary hypertension.The pathogenesis of hypoxic pulmonary hypertension is complex, and its mechanism has not been fully elucidated.The previous studies have shown abnormally elevated levels of free Ca + in the cytoplasm of pulmonary artery smooth muscle cells to be the predominant drivers of pulmonary hypertension , causing continuous contraction and remodeling of the pulmonary vessels.This article briefly summarizes the mechanism of hypoxia-induced imbalance in calcium homeostasis in pulmonary artery smooth muscle cells, together with its related drug research, based on the existing literature.Hypoxia induces an imbalance in calcium homeostasis in pulmonary artery smooth muscle cells by regulating hypoxia-inducible factor-1, K+ , store-operated calcium channel, receptor-operated calcium channel, the Ca +-sensing myosin contractile mechanism by binding to calmodulin, leading to pulmonary vasoconstriction.Ca + can also activate PKC/ MAPKs and PI3K/Akt/mTOR pathways, leading to pulmonary vascular remodeling.

An Index to Assess Overwork-Related Adverse Effects on Employees Under the Occupational Safety and Health Act in Taiwan

Background@#The present study aimed to digitally evaluate the risk of overwork-related adverse effects (OrAEs) among employees from various occupational categories in Taiwan. @*Methods@#Anonymous data of employees from seven companies/factories providing occupational health services were analyzed. The studied population comprised 5505 employees, and the data analyzed included employment duration, working hours, shift work schedules, and health checkup results. The risk for OrAEs was assessed by an index, Karo index (0-4, the larger the value, the higher the risk for OrAEs) obtained using a risk matrix made up of cardiocerebral and occupational risk factors. Karo index values of 3 and 4 were categorized as at high risk for OrAEs (h-OrAEs). @*Results@#The 5505 employees had an average employment duration of 8.5 years and a mean age of 39.4 years. The prevalence rates for h-OrAEs of the seven companies/factories ranged from 3.9% to 34.2%. There were significant differences in prevalence rates for h-OrAEs between employees of retail stores and high-tech manufacturing factories. Multivariate analysis results indicated that workers of high-tech manufacturing factories had significantly higher risk for h-OrAEs compared with retail store workers. @*Conclusion@#In terms of satisfying health risk management and legal requirements in Taiwan, the newly issued Karo index, which covers a wide range of occupational risk factors, can serve as an assessment and a warning tool for managing the risk of OrAEs in workplaces. To reduce risks for h-OrAEs, active and prudent control of cerebrocardiovascular risks and working hours is recommended.

Effects of early life PM2.5 exposure on prefrontal cortex of offspring male rats / 中国应用生理学杂志

Objective: To investigate the effects of PM2.5 exposure at different stages of early life on the prefrontal cortex of offspring rats. Methods: Twelve pregnant SD rats were randomly divided into four groups: Control group (CG), Maternal pregnancy exposure group (MG), Early postnatal exposure group (EP) and Perinatal period exposure group (PP), 3 rats in each group. The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM2.5. MG was exposed from gestational day (GD) 1 to GD21. EP was exposed from postnatal day (PND) 1 to PND21, and PP was exposed from GD1 to PND21. After exposure, the prefrontal cortex of 6 offspring rats in each group was analyzed. HE staining was used to observe the pathological damage in the prefrontal cortex. ELISA was employed to detect neuroinflammatory factors, and HPLC/MSC was applied to determine neurotransmitter content. Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers, respectively. Results: Compared with MG and CG, the pathological changes of prefrontal cortex in PP and EP were more obvious. Compared with MG and CG, the neuroinflammatory factors (IL-1, IL-6, TNF-α) in PP and EP were increased significantly (P＜0.01), the level of MT were decreased significantly (P＜0.05), and the level of oxytocin (OT) showed a downward trend; the level of neurotransmitter ACh was also increased significantly (P＜0.01). Compared with MG and CG, the GFAP level of PP and EP showed an upward trend, the level of oxidative stress index SOD in PP and EP was decreased significantly (P＜0.01), and the level of ROS was increased significantly (P＜0.01). Compared with the offspring rats of CG and MG, the CAT level of PP was decreased significantly (P＜0.01, P＜0.05). Compared with the offspring rats of CG, the CAT level of EP was decreased significantly (P＜0.05). There was no significant difference in IL-1, IL-6, TNF-α, MT, OT, ACh, GFAP, SOD, ROS and CAT levels between PP and EP, or MG and CG. Conclusion: PM2.5 exposure in early life has adverse effects on the prefrontal cortex of offspring male rats, and early birth exposure may be more sensitive.

Bioactive sesquineolignans from the twigs of Litsea cubeba / 中国天然药物

In a continuing search for biological natural products with structure diversity from traditional Chinese herbs, five new sesquineolignans (1-5) were isolated from an ethyl acetate extract of the twigs of Litsea cubeba. Their structures were elucidated based on MS, 1D and 2D NMR spectroscopic data, as well as experimental electronic circular dichroism (ECD) spectra. Compounds 1-5 showed moderate inhibitory effects against LPS-induced NO production in RAW264.7 macrophages, with IC

Impact of thymosin α1 as an immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection: a propensity score-matched analysis / 中华医学杂志(英文版)

BACKGROUND@#There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients.@*METHODS@#A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients.@*RESULTS@#After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy.@*CONCLUSION@#Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.