Effect of systemic lupus erythematosus on the ovarian reserve: A systematic review and meta-analysis.

OBJECTIVE: Systemic Lupus Erythematosus (SLE) is an autoimmune disease that occurs at higher rates in young women. Evidence suggests that SLE may be associated with ovarian dysfunction. Therefore, it is crucial to investigate the possible effects of SLE on ovarian reserve function. METHODS: PubMed, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases were searched from inception to July 2023 to identify studies that compared ovarian reserve in patients with SLE to that of healthy individuals. The study examined anti-müllerian hormone (AMH), antral follicle count (AFC), and follicle-stimulating hormone (FSH) as outcomes. RESULTS: Thirteen studies (n=1017) were eligible for meta-analysis. Females with SLE had significantly lower levels of AMH (weighted mean difference [WMD]: -1.07, 95% confidence interval [CI]: -1.37 to -0.76, P<0.001) and AFC (WMD: -3.46, 95% CI: -4.57 to -2.34, P<0.001). There was no significant difference in FSH levels. Subgroup analyses by age of onset revealed that SLE patients with adult-onset had significantly lower AMH levels (WMD: -1.44, 95% CI: -1.71 to -1.18, P<0.001), lower AFCs (WMD: -3.11, 95% CI: -3.60 to -2.61, P<0.001) and higher FSH levels (WMD: 0.60, 95% CI: 0.15 to 1.05, P<0.01). However, SLE patients with juvenile-onset did not exhibit significant differences in their AMH and FSH levels, except for AFCs (WMD: -7.27, 95% CI: -12.39 to -2.14, P<0.01). CONCLUSION: The impact of SLE on ovarian reserve is significant, and the effect may be particularly severe in cases of adult-onset SLE.

How Does Spino-Pelvic Fixation Affect Post-Operative Compensatory Mechanisms in Adult Spinal Deformity?

STUDY DESIGN: Retrospective single-center multi-surgeon cohort study. OBJECTIVES: Compare the post-operative changes in the compensatory mechanisms of the sagittal balance according to the type of pelvic fixation: S2-Alar-iliac screws (S2AI) vs iliac screws (IS) in patients with Adult spine deformity (ASD). METHODS: ASD patients who underwent spino-pelvic fixation and remained with a PI-LL >10° mismatch post-operatively were included. Pre-operative and 1-year-follow-up PI, Lumbar lordosis (LL), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), femur obliquity angle (FOA), knee flexion angle (KFA) and ankle flexion angle (AFA) were analyzed on EOS imaging. Patients were categorized based on their pelvic fixation type (S2AI vs IS), and the pre-operative to 1-year-post-operative changes (ΔX°) in the compensatory mechanisms were compared between groups. RESULTS: Patients with S2AI (n = 53) and those with IS (n = 26) screws were comparable at baseline. ΔSS averaged 9.87° in the S2AI compared to 13.2° in the IS (P = .001), whereas the ΔKFA reached 6.01° in the S2AI as opposed to 3.06° in the IS (P = .02). The ΔPT was comparable between both groups (6.35°[S2AI group] vs 5.21°[ISgroup], P = .42). ΔTK, ΔLL, ΔFOA and ΔAFA were comparable between both groups. CONCLUSION: The type of pelvic fixation impacts significantly the post-operative compensatory mechanisms in patients with ASD. Patients with S2AI screws are more likely to compensate their remaining post-operative PI-LL mismatch through their knees and less likely through their pelvis compared to patients with IS, despite similar changes in PT. This could be explained by an increased SI joint laxity in ASD patient and the lower resistance of the iliac connectors to the junctional mechanical stresses, allowing for sacro-iliac joint motion in patients with IS.

Highly Efficient Wavelength-Tunable Circularly Polarized Luminescence Film Constructed by Responsive Chiral Aggregation-induced Emission Luminophore.

Key Lab of Environment-friendly Chemistry and Circularly polarized luminescent (CPL) materials with multitudinous inherent advantages shows extensive application. In this work, we prepare a kind of highly efficient wavelength-tunable CPL free-standing films by responsive chiral aggregation-induced emission mesogen. Firstly, the pyridine-functionalized tetraphenylethene monomer (MPy) is designed and synthesized. Then, the different ration of the monomer MPy mixed with the liquid crystal (LC) reactive monomer (LC242) to fabricate a free-standing film by photopolymerization. The obtained film presents efficient CPL with a constant luminescence asymmetry factor (glum ) of +0.75, as well as sensitive wavelength tunability. Finally, this wavelength-tunable CPL film with both fluorescence and CPL modes is successfully applied in anti-counterfeiting and information encryption. This work provides a simple way to construct CPL apparatus with adjustable luminescence wavelength and high glum .

Expert Consensus on Acute Respiratory Failure in Critically Ill Cancer Patients (2023) / 中国医学科学杂志(英文版)

Objective This consensus aims to provide evidence-based recommendations on common questions in the diagnosis and treatment of acute respiratory failure (ARF) for critically ill cancer patients.Methods We developed six clinical questions using the PICO (Population, Intervention, Comparison, and Outcome) principle in diagnosis and treatment for critical ill cancer patients with ARF. Based on literature searching and meta-analyses, recommendations were devised. The GRADE (Grading of Recommendation Assessment, Development and Evaluation) method was applied to each question to reach consensus in the expert panel. Results The panel makes strong recommendations in favor of (1) metagenomic next-generation sequencing (mNGS) tests may aid clinicians in rapid diagnosis in critically ill cancer patients suspected of pulmonary infections; (2) extracorporeal membrane oxygenation (ECMO) therapy should not be used as a routine rescue therapy for acute respiratory distress syndrome in critically ill cancer patients but may benefit highly selected patients after multi-disciplinary consultations; (3) cancer patients who have received immune checkpoint inhibitor therapy have an increased incidence of pneumonitis compared with standard chemotherapy; (4) critically ill cancer patients who are on invasive mechanical ventilation and estimated to be extubated after 14 days may benefit from early tracheotomy; and (5) high-flow nasal oxygen and noninvasive ventilation therapy can be used as a first-line oxygen strategy for critically ill cancer patients with ARFs. A weak recommendation is: (6) for critically ill cancer patients with ARF caused by tumor compression, urgent chemotherapy may be considered as a rescue therapy only in patients determined to be potentially sensitive to the anticancer therapy after multidisciplinary consultations. Conclusions The recommendations based on the available evidence can guide diagnosis and treatment in critically ill cancer patients with acute respiratory failure and improve outcomes.

Prevalence and influencing factors of work-related musculoskeletal disorders among workers in chemical pharmaceutical industry / 环境与职业医学

Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems in the world. Pharmaceutical industry is an important part of China's national economy. At present, there are few related studies reported at home and abroad. Objective To investigate the status and influencing factors of WMSDs in chemical pharmaceutical industry. Methods A cross-sectional epidemiological survey was conducted among all workers from three chemical pharmaceutical enterprises in Guangzhou. The Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, symptoms of musculoskeletal disorders, types of work, work organization, and and work postures. Multiple logistic regression method was used to analyze the risk factors of WMSDs in chemical pharmaceutical workers. Results In this study, 563 workers were selected as subjects. The total prevalence rate of WMSDs symptoms in the chemical pharmaceutical workers was 43.9% (247/563), and the leading body part-specific prevalence rate from high to low was 34.3% in the lower back, 24.3% in the upper back, 24.0% in the shoulders, and 23.8% in the neck. The prevalence rate of WMSDs symptoms in multiple body parts (30.0%) was 2.16 times higher than that in single body part (13.9%), and the prevalence rate of WMSDs symptoms in four body parts was the highest (11.4%). The results of multiple logistic regression analysis showed that age ≥50 years (reference age <30 years) (OR=2.140, 95%CI: 1.054-4.345), often or very often (reference never/rarely) long-time head rotating (OR=2.695, 95%CI: 1.753-4.142) and long-time keeping arms above shoulders (OR=1.902, 95%CI: 1.108-3.265) increased the risk of reporting WMSDs symptoms (P<0.05). Regarding education level, workers with high school and technical secondary school (OR=0.333, 95%CI: 0.175-0.636) or college and above (OR=0.413, 95%CI: 0.216-0.790) education had a lower risk of reporting WMSDs symptoms than those with middle school or below (P<0.05). Conclusion The prevalence rate of reporting WMSDs symptoms in chemical pharmaceutical industry is high, the involving body parts are lower back, upper back, shoulders, and neck, and reporting simultaneous occurrence of WMSDs symptoms in multiple body parts is common. The chemical pharmaceutical manufacturers can reduce the risk of WMSDs by strengthening the training on workers' ergonomics knowledge, paying attention to the less educated personnel, protecting the elderly workers, and avoiding awkward work postures, like rotating head for a long time and raising arms over shoulders.

Work-related musculoskeletal disorders and their influencing factors among workers in a furniture factory / 环境与职业医学

Background Furniture manufacturing is one of the typical labor-intensive industries, and workers in this industry face a high risk of work-related musculoskeletal disorders (WMSDs), which seriously affect the physical and mental health of workers. Objective To explore the prevalence and potential risk factors of WMSDs among workers in a large-scale furniture manufacturing factory. Methods A cross-sectional study of 3431 workers in a furniture factory in Guangdong Province was conducted from September to December 2019. Information including reported WMSDs in various body parts in the past year, demographic characteristics, work organization factors, job characteristics, and work postures was collected by an electronic version of Musculoskeletal Disorders Questionnaire. Pearson χ2 test and binary logistic regression were used to analyze the risk factors leading to WMSDs. Results The overall prevalence rate of WMSDs was 32.12% (1102/3431). The most common WMSDs symptoms occurred in the neck (16.85%), followed by the feet (15.27%), shoulders (14.81%), and hands (14.25%). The prevalence rates of WMSDs in the neck, shoulders, elbows, hands, legs, and feet were significantly different among different types of work (P<0.05). The results of multiple logistic regression analysis showed that individual factors, work organization factors, job characteristics, and awkward work postures were associated with the frequency of reporting WMSDs in specific parts of workers. Comparatively poor physical health (including moderate, poor, and very poor) was positively correlated with neck, shoulder, hand, and foot WMSDs (OR=1.479-4.077); working with an uncomfortable posture (OR=1.983) and doing the same task almost every day (OR=1.783) were positively correlated with neck pain; doing the same task almost every day (OR=2.408) and neck twisting for a long time (OR=1.830) were positively correlated with shoulder pain; bending wrists up and down frequently (OR=1.948) and bending wrists for a long time (OR=2.081) were positively correlated with hand pain; prolonged standing (OR=1.953) and often working overtime (OR=1.627) were positively correlated with feet pain; sufficient rest time was negatively correlated with WMSDs in the neck, shoulders, hands, and foot (OR=0.544-0.717). Conclusion The prevalence rate of WMSDs in furniture manufacturing workers is relatively high, and neck, feet, shoulders, and hands are the most involved body parts. The frequency of reporting WMSDs is related to individual factors, work organization factors, job characteristics, and awkward work postures.

Effect and mechanism of Xihuang Pills on rats with precancerous lesions of breast / 中国中药杂志

The purpose of this study was to explore the effect and mechanism of Xihuang Pills on rats with precancerous lesions of the breast. Of 48 healthy female rats, 8 were randomly selected as blank group, and the other 40 were treated with 7,12-dimethylbenzanthracene(DMBA) combined with estrogen and progestin to establish a model of precancerous lesions of the breast. The successfully modeled rats were randomly divided into a model group, a tamoxifen group(1.8 mg·kg~(-1)·d~(-1)), a Xihuang Pills low-dose group(0.3 g·kg~(-1)·d~(-1)), a medium-dose group(0.6 g·kg~(-1)·d~(-1)) and a high-dose group(1.2 g·kg~(-1)·d~(-1)). After 30 days of admi-nistration, the histopathological changes of viscera and breast were observed by haematoxylin and eosin(HE) staining, and the visceral index was calculated. Enzyme linked immunosorbent assay(ELISA) was used to detect the contents of estradiol(E_2) and progesterone(P) in serum. The protein expressions of vascular endothelial growth factor(VEGF) and fibroblast growth factor 2(FGF2) were detected by immunohistochemistry. The protein expressions of VEGF, vascular endothelial growth factor receptor 2(VEGFR2), phosphorylated-vascular endothelial growth factor receptor 2(p-VEGFR2), B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were detected by Western blot and the mRNA expressions of VEGF, FGF2, CXC-chemokine receptor 4(CXCR4), cysteine aspartic acid-specific protease(caspase-3), and stromal cell-derived factor 1(SDF-1) were detected by real-time polymerase chain reaction(RT-PCR). HE staining revealed that the model group had some liver and kidney damages and severe hyperplastic mammary tissue, while the Xihuang Pills high-dose group had mild hyperplasia. Compared with the model group, the Xihuang Pills groups had lo-wer ovarian coefficient(P<0.05 or P<0.01) and Xihuang Pills high-dose group had lower uterine coefficient(P<0.01). ELISA results showed that compared with the model group, expressions of E_2 and P in Xihuang Pills high-dose group were significantly decreased(P<0.05 or P<0.01). Immunohistochemistry, Western blot and RT-PCR indicated that compared with the conditions in the model group, the protein and mRNA expressions of VEGF and FGF2 in the Xihuang Pills groups were down-regulated(P<0.05 or P<0.01), and the protein expression of Bcl-2 was lowered(P<0.01); there was a decrease in the protein expressions of VEGFR2 and p-VEGFR2(P<0.01), a down-regulation in the mRNA expressions of CXCR4 and SDF-1(P<0.01), while an increase in the mRNA expression of caspase-3(P<0.01) in both Xihuang Pills medium-dose and high-dose groups; the protein expression of Bax in Xihuang Pills high-dose group was increased(P<0.01). The above results indicated that Xihuang Pills can effectively intervene in precance-rous lesions of the breast, and the mechanism may be related to the regulation of E_2 and P secretion as well as the inhibition of angiogenesis and chemokine receptor expression, thus controlling the occurrence of precancerous lesions of the breast in rats.

A new dihydrochalcone from Humulus scandens / 中国中药杂志

To study the chemical constituents from the stems and leaves of Humulus scandens, this study isolated thirteen compounds by different chromatographic methods including silica gel column, ODS, Sephadex LH-20 and preparative HPLC. Based on comprehensive analysis, the chemical structures were elucidated and identified as citrunohin A(1), chrysosplenetin(2), casticin(3), neoechinulin A(4), ethyl 1H-indole-3-carboxylate(5), 3-hydroxyacetyl-indole(6),(1H-indol-3-yl) oxoacetamide(7), inonotusic acid(8), arteannuin B(9), xanthotoxol(10), α-tocopherol quinone(11), eicosanyl-trans-p-coumarate(12), and 9-oxo-(10E,12E)-octadecadienoic acid(13). Among them, compound 1 was a new dihydrochalcone, and the other compounds were obtained from H. scandens for the first time.

Effect of Age and Sex on Stroke Mortality of Young and Middle-aged Adults in China, 2002-2019, and Predictions to 2030 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to examine the trends in stroke mortality among young and middle-aged adults in China.@*METHODS@#Data were obtained from the China national vital registration system. Significant changes in mortality were assessed by Joinpoint regression. Age-period-cohort analysis was used to explain the reasons for the changes. Future mortality and counts were predicted by the Bayesian age-period-cohort model.@*RESULTS@#Between 2002 and 2019, a total of 6,253,951 stroke mortality in young and middle-aged adults were recorded. The age-adjusted mortality rates (AAMRs) of women showed a downward trend. The annual percent changes (APC) were -3.5% (-5.2%, -1.7%) for urban women and -2.8% (-3.7%, -1.9%) for rural women. By contrast, the AAMRs per 100,000 for rural men aged 25-44 years continued to rise from 9.40 to 15.46. The AAMRS for urban men aged 25-44 years and urban and rural men aged 45-64 years did not change significantly. Between 2020 and 2030, the projected stroke deaths are 1,423,584 in men and 401,712 in women.@*CONCLUSION@#Significant sex and age disparities in the trends of stroke mortality among young and middle-aged adults were identified in China. Targeted health policy measures are needed to address the burden of stroke in the young generation, especially for rural men, with a focus on the prevention and management of high risk factors.

Comparison of in vivo plasma pharmacokinetics and urine excretion of main components in Xihuang Formula in rats with precancerous lesions of breast cancer / 中国中药杂志

The UPLC-MS/MS was established for the determination of acetyl-11-keto-beta-boswellic acid(AKBA) and β-boswellic acid(β-BA), the main active components of Olibanum and Myrrha extracts in Xihuang Formula, in rat plasma and urine. The effects of compatibility on the pharmacokinetic behaviors of AKBA and β-BA in rats were investigated, and the differences in pharmacokinetic behaviors between healthy rats and rats with precancerous lesions of breast cancer were compared. The results showed that compared with RM-NH and RM-SH groups, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05 or P<0.01), T_(max) decreased(P<0.05 or P<0.01), and C_(max) increased(P<0.01) after compatibility. The trends of AKBA and β-BA were the same. Compared with RM-SH group, the T_(max) decreased(P<0.05), C_(max) increased(P<0.01), and the absorption rate increased in the normal group of Xihuang Formula. The results of urinary excretion showed that there was a decreasing trend in the urinary excretion rate and total urinary excretion of β-BA and AKBA after compatibility, but there was no statistical difference. Compared with normal group of Xihuang Formula, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05), T_(max) increased(P<0.05), and the clearance rate decreased in the breast precancerous lesion group. AUC_(0-t) and AUC_(0-∞) of AKBA showed an increasing trend, the in vivo retention time was prolonged, and the clearance rate was reduced, but there was no significant difference compared with the normal group. The cumulative urinary excretion and urinary excretion rate of β-BA and AKBA decreased under pathological conditions, indicating that pathological conditions could affect the in vivo process of β-BA and AKBA, and reduce their excretion in the form of prototype drugs, showing different pharmacokine-tic characteristics from normal physiological conditions. In this study, UPLC-MS/MS analysis method was established, which was sui-table for in vivo pharmacokinetic analysis of β-BA and AKBA. This study laid a foundation for the development of new dosage forms of Xihuang Formula.

Basal Forebrain Cholinergic Innervation Induces Depression-Like Behaviors Through Ventral Subiculum Hyperactivation / 神经科学通报·英文版

Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.

Assessing the Performance of Prognostic Scores in Patients with Spinal Metastases from Lung Cancer Undergoing Non-surgical Treatment

Methods@#Data analysis was carried out to identify the variables that had a significant impact on survival. For all patients with spinal metastasis from lung cancer who received non-surgical treatment, the Tomita score, revised Tokuhashi score, modified Bauer score, Van der Linden score, classic SORG algorithm, SORG nomogram, and NESMS were calculated. The performance of the scoring systems was assessed by using receiver operating characteristic (ROC) curves at 3 months, 6 months, and 12 months. The predictive accuracy of the scoring systems was quantified using the area under the ROC curve (AUC). @*Results@#A total of 127 patients are included in the present study. The median survival of the population study was 5.3 months (95% confidence interval [CI], 3.7–9.6 months). Low hemoglobin was associated with shorter survival (hazard ratio [HR], 1.49; 95% CI, 1.00–2.23; p =0.049), while targeted therapy after spinal metastasis was associated with longer survival (HR, 0.34; 95% CI, 0.21–0.51; p <0.001). In the multivariate analysis, targeted therapy was independently associated with longer survival (HR, 0.3; 95% CI, 0.17–0.5; p <0.001). The AUC of the time-dependent ROC curves for the above prognostic scores revealed all of them performed poorly (AUC <0.7). @*Conclusions@#The seven scoring systems investigated are ineffective at predicting survival in patients with spinal metastasis from lung cancer who are treated non-surgically.

In vitro transcribed (IVT) mRNA drugs: technical progress and application prospect / 药学学报

The in vitro transcribed (IVT) mRNA technology has progressed rapidly and the application of mRNA vaccines in the COVID-19 pandemic made it become the most talked-about topic. Compared with protein drugs, IVT mRNA has a lower cost; it can be modular produced and its sequence can be modified easily, so it has a broad application prospect. However, due to its short history, mRNA drugs face the problem of lacking sufficient clinical data, and there is no quality control standard for mRNA drugs except mRNA vaccines. We overview the sequence design, delivery vectors, administration, application prospect and safety considerations of mRNA drugs. We also discussed the quality control of mRNA drugs briefly.

Trichostatin C attenuates TNFα-induced inflammation in endothelial cells by up-regulating Krüppel-like factor 2 / 药学学报

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

Identification and analysis of AP2/ERF gene family of Panax notoginseng and function of PnDREB84 gene / 药学学报

The AP2/ERF gene family is one of the largest transcription factor families in the plant kingdom, and plays an important role in response to biological and abiotic stresses, plant hormone responses, and plant growth and development. In this study, the AP2/ERF family of Panax notoginseng was identified by bioinformatics methods, and the physicochemical properties, structure, phylogenetic relationship, expression pattern and function of PnDREB4 gene of the family were analyzed. The results showed that 140 AP2/ERF family members were identified in P. notoginseng, which were divided into DREB, ERF, AP2, RAV and Sololit subgroups. The physicochemical properties and motifs of proteins were similar among the subgroups. There were 34 differentially expressed genes in the AP2/ERF family of Fusarium oxysporum infected P. notoginseng plants, and 19 genes were up-regulated. The expression level of PnDREB84 was up-regulated with the extension of Fusarium oxysporum infection time in the range of 0-96 h. The content of ABA and SA in P. notoginseng plants overexpressing PnDREB84 gene increased after 4 ℃ stress. The results showed that PnDREB84 gene plays a dual regulatory role in the process of biological stress and abiotic stress. PnDREB84 gene can be used as a potential molecular marker for the breeding of new varieties of P. notoginseng. The identification of AP2/ERF transcription factor and function analysis of PnDREB84 gene of P. notoginseng provided data support for the analysis of stress resistance mechanism of P. notoginseng and the breeding of new varieties.

Advances in clinical and safety studies of phosphodiesterase 4 inhibitors / 药学学报

Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.

Establishment and evaluation of a predictive model for clinical remission of advanced esophageal squamous cell carcinoma after neoadjuvant chemotherapy / 中国胸心血管外科临床杂志

@#Objective     To investigate the influencing factors for the clinical remission of advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemotherapy, establish an individualized nomogram model to predict the clinical remission of advanced ESCC with neoadjuvant chemotherapy and evaluate its efficacy, providing serve for the preoperative adjuvant treatment of ESCC. Methods     The clinical data of patients with esophageal cancer who underwent neoadjuvant chemotherapy (nedaplatin 80 mg/m2, day 3+docetaxel 75 mg/m2, day 1, 2 cycles, 21 days per cycle interval) in the Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College from February 2016 to August 2020 were analyzed retrospectively. According to the WHO criteria for efficacy assessment of solid tumors, tumors were divided into complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD). CR and PR were defined as effective neoadjuvant chemotherapy, and SD and PD were defined as ineffective neoadjuvant chemotherapy. Univariate and multivariate analyses were used to analyze the influencing factors for the short-term efficacy of neoadjuvant chemotherapy. The R software was used to establish a nomogram model for predicting of the model. C-index, calibration curve and receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the nomogram. Results     Finally 115 patients were enrolled, including 93 males and 22 females, aged 40-75 (64.0±8.0) years. After receiving docetaxel+nedaplatin neoadjuvant chemotherapy for 2 cycles, there were 9 patients with CR, 56 patients with PR, 43 patients with SD and 7 patients with PD. Among them, chemotherapy was effective (CR+PR) in 65 patients and ineffective (SD+PD) in 50 patients, with the clinical effective rate of about 56.5%(65/115). Univariate analysis showed that there were statistical differences in smoking history, alcoholism history, tumor location, tumor differentiation degree, and cN stage before chemotherapy between the effective neoadjuvant chemotherapy group and the ineffective neoadjuvant chemotherapy group (P<0.05). Logistic regression analysis showed that low-differentiation advanced ESCC had the worst clinical response to neoadjuvant chemotherapy, moderately-highly differentiated ESCC responded better (P<0.05). Stage cN0 advanced ESCC responded better to neoadjuvant chemotherapy than stage cN1 and cN2 (P<0.05). The C-index and the area under the ROC curve of the nomogram were both 0.763 (95%CI 0.676-0.850), the calibration curve fit well, the best critical value of the nomogram calculated by the Youden index was 70.04 points, and the sensitivity and specificity of the critical value were 80.0% and 58.0%, respectively. Conclusion    The established clinical prediction model has good discrimination and accuracy, and can provide a reference for individualized analysis of the clinical remission of advanced ESCC with neoadjuvant chemotherapy and the screening of new adjuvant treatment subjects.

Inspiratory muscle training can improve the breathing, balance and walking of persons with Parkinson′s disease / 中华物理医学与康复杂志

Objective:To observe any effect of threshold pressure loaded inspiratory muscle training on the balance of persons with Parkinson′s disease (PD).Methods:Forty-eight persons with PD were randomly divided into an observation group and a control group, each of 24. Both groups were given conventional neurological drug treatment and conventional rehabilitation training. The observation group additionally completed inspiratory muscle training using a threshold pressure load trainer, 5 days per week for 8 weeks. Before and after the treatment, both groups′ inspiratory muscle functioning was quantified using ultrasound to assess diaphragm mobility and thickness, and maximum inspiratory pressure (MIP). Balance was quantified using Trunk Injury Scale (TIS) scoring, the Berg Balance Scale (BBS), limits of stability (LOS), and the timed up and go test (TUGT). Walking was evaluated using the 10-metre walk test (10MWT) and the Dynamic Gait Index (DGI).Results:After the treatment all of the indicators had improved significantly in both groups, on average, but those of the observation group were then significantly better. Correlation analysis showed that the difference in MIP of the observation group before and after treatment was significantly negatively correlated with the TUGT and 10MWT times.Conclusion:Threshold pressure loaded inspiratory muscle training combined with conventional rehabilitation therapy significantly improves the inspiratory muscle strength, balance and walking of persons with PD.

Caffeic acid phenethyl ester improves peritoneal dialysis-associated peritoneal fibrosis by alleviating oxidative stress injury through activating nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway / 中华肾脏病杂志

Objective:To investigate whether caffeic acid phenethyl ester (CAPE) would improve peritoneal dialysis (PD)-associated peritoneal fibrosis by alleviating oxidative stress through activating nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.Methods:Thirty-two male Sprague-Dawley rats were randomly divided into four groups by the random number table: control (CON) group (0.9% normal saline 20 ml/d intraperitoneal injection), CAPE group (0.9% normal saline 20 ml/d+CAPE 10 mg·kg -1·d -1 intraperitoneal injection), PD group [4.25% glucose peritoneal dialysis fluid (PDF) 20 ml/d intraperitoneal injection with lipopolysaccharide 0.6 mg/kg intraperitoneal injection at day 1, 3, 5 and 7], and PD+CAPE group (CAPE 10 mg·kg -1·d -1 intraperitoneal injection in addition to PD group), with 8 rats per group. On day 28, rats were euthanized after peritoneal equilibration test, and then the parietal peritoneum and omentum were collected for follow-up tests. To further investigate the mechanism, primary peritoneal mesothelial cells (PMCs) of rats were isolated and cultured. The PMCs were stimulated with 2.5% glucose PDF and added with 5 μmol/L CAPE intervention. The Nrf2 inhibitor (ML385) was used to identify whether CAPE protected PMCs from PDF by activating the Nrf2/HO-1 pathway. Histopathological staining was used to detect structural changes of the peritoneum, and immunohistochemical analysis was performed on cleaved caspase-3, Bax, α-smooth muscle actin (α-SMA), fibronectin (FN), and typeⅠ collagen (Col-Ⅰ) protein. Western blotting was used to detect the protein expression of α-SMA, FN, transforming growth factor-β1 (TGF-β1), HO-1 and nuclear Nrf2 (N-Nrf2). The apoptosis detection kit was used to detect apoptosis and flow cytometry was used to detect reactive oxygen species (ROS) in PMCs. The malondialdehyde (MDA) and superoxide dismutase (SOD) activity detection kit were used to detect MDA content and SOD activity. Cell immunofluorescence was used to analyze the protein expression of Nrf2 in PMCs. Results:Compared with the CON group, the PD group had thicker peritoneum, and the expression levels of cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰand MDA in peritoneum were significantly higher, while HO-1, N-Nrf2 protein expression and SOD activity were lower (all P<0.05). Compared with the PD group, the parietal peritoneum morphology of CAPE+PD group was improved, accompanied by reduced cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰ protein expression, and MDA content, while N-Nrf2, HO-1 protein expression, and SOD activity were higher (all P<0.05). Compared with the CON group, the PD group had significantly lower ultrafiltration volume and higher peritoneal permeability (both P<0.05). After CAPE intervention, the peritoneal transport function of the rats was significantly improved ( P<0.05). In cultured PMCs, PDF inhibited nuclear translocation of Nrf2 and protein expression of HO-1, and upregulated intracellular ROS level. In addition, PDF increased cell apoptosis and the protein expression levels of α-SMA, TGF-β1 and FN (all P<0.05). CAPE activated nuclear translocation of Nrf2, increased HO-1 protein expression, downregulated intracellular ROS level, and partially reversed PDF-induced cell apoptosis and epithelial- mesenchymal transition (all P<0.05). The protective effects of CAPE on PMCs were partially abolished by ML385 (all P<0.05). Conclusions:CAPE can reduce PD-induced PMCs apoptosis and epithelial-mesenchymal transition by attenuating oxidative stress, and significantly improve peritoneal fibrosis and ultrafiltration function. The beneficial effects of CAPE on peritoneum are related to activation of Nrf2/HO-1 pathway.

Prevalence and risk factors of overactive bladder in elderly women with stress urinary incontinence / 中华老年医学杂志

Objective:To explore the risk factors of overactive bladder(OAB)syndrome in older women with stress urinary incontinence(SUI).Methods:In this cross-sectional study, 157 elderly women with SUI, aged 60-88(65.6±5.4)years, were recruited from Qingshan District Maternal and Child Health Hospital and areas serviced by Fozuling Community Service Center in Wuhan between October to November 2020.Data collection included a questionnaire covering general information, dietary habits, childbirth history, medical history, the urogenital distress inventory(UDI-6)and the overactive bladder symptom score(OABSS), and physical examinations on curvature of the spine, pelvic floor muscle strength and pelvic floor ultrasound imaging.Results:A total of 157 elderly women with SUI were included in the study and the prevalence of OAB was 17.2%(27 cases). The prevalence of OAB was 17.6%(25 cases)among 142 patients with mild SUI and 13.3%(2 cases)among 15 patients with moderate or severe SUI, but SUI severity was not correlated with the prevalence of OAB( χ2=0.003, P>0.05). The UDI-6 score was 2.39±2.04 and the OABSS score was 3.70±2.48, with a positive correlation between OABSS and UDI-6( r=0.254, P<0.01), suggesting that OAB had a negative effect on the quality of life of patients with SUI.Multivariate Logistic regression analysis on factors with P<0.3 in the univariate analysis showed that number of pregnancies( P<0.01), anterior vaginal wall prolapse( P<0.05), and abnormal inclination of the pelvis( P=0.05)were associated with the prevalence of OAB.Regarding the number of pregnancies, the risk of OAB increased with 2-3 pregnancies( OR=1.46, 95% CI: 0.25-8.56)and with 3 pregnancies or more( OR=4.29, 95% CI: 0.79-23.18), compared with the prevalence at no more than 1 pregnancy.Compared with patients without anterior vaginal wall prolapse, Ⅰ-Ⅱ degree prolapse increased the risk of OAB( OR=4.21, 95% CI: 1.40-12.63), and third-degree prolapse further increased the risk( OR=11.48, 95% CI: 1.37-96.17). Compared with patients with normal inclination of the pelvis, anterior or posterior pelvis inclination promoted the occurrence of OAB( OR=3.46, 95% CI: 1.23-9.73; OR=2.62, 95% CI: 0.54-12.71). Conclusions:OAB has a negative impact on the quality of life of elderly women with SUI.Pregnancy, anterior vaginal prolapse and abnormal inclination of the pelvis promote the occurrence of OAB.