Toxicity comparison and risk assessment of two chlorinated organophosphate flame retardants (TCEP and TCPP) on Polypedates megacephalus tadpoles.

Tris(2-chloroethyl) phosphate (TCEP) and tris(1­chloro-2-propyl) phosphate (TCPP) are widely used as chlorinated organophosphate flame retardants (OPFRs) due to their fire-resistance capabilities. However, their extensive use has led to their permeation and pollution in aquatic environments. Using amphibians, which are non-model organisms, to test the toxic effects of OPFRs is relatively uncommon. This study examined the acute and chronic toxicity differences between TCEP and TCPP on Polypedates megacephalus tadpoles and evaluated the potential ecological risks to tadpoles in different aquatic environments using the risk quotient (RQ). In acute toxicity assay, the tadpole survival rates decreased with increased exposure time and concentrations, with TCEP exhibiting higher LC50 values than TCPP, at 305.5 mg/L and 70 mg/L, respectively. In the chronic assay, prolonged exposure to 300 µg/L of both substances resulted in similar adverse effects on tadpole growth, metamorphosis, and hepatic antioxidant function. Based on RQ values, most aquatic environments did not pose an ecological risk to tadpoles. However, the analysis showed that wastewater presented higher risks than rivers and drinking water, and TCPP posed a higher potential risk than TCEP in all examined aquatic environments. These findings provide empirical evidence to comprehend the toxicological effects of OPFRs on aquatic organisms and to assess the safety of aquatic environments.

Trends in nutritional status and factors affecting prognostic nutritional index in ovarian cancer patients during chemotherapy: a prospective longitudinal study based on generalized estimating equations.

PURPOSE: Numerous studies have investigated the relationships between nutritional status and the prognosis of ovarian cancer (OC). However, the majority of these studies have focused on pre-chemotherapy malnutrition, with limited attention given to dynamic changes in nutritional status during chemotherapy and the associated risk factors affecting the prognostic nutritional index (PNI) in OC women. This study aims to explore the variation trend in the nutritional status of OC women over time during chemotherapy and assess its predictive factors. METHODS: A prospective longitudinal study was conducted from January 2021 to August 2023. Body mass index (BMI), PNI, Nutritional Risk Screening (NRS) 2002, serum albumin, and prealbumin measurements were utilized to assess the nutritional status of OC women. Data were collected through face-to-face interviews before initial chemotherapy (T0) and during the first (T1), third (T2), and fifth (T3) cycles of chemotherapy. Generalized Estimating Equations (GEE) were employed for the analysis of potential predictive factors. RESULTS: A total of 525 OC women undergoing chemotherapy completed the study. Significantly varied levels of BMI, PNI, and serum concentrations of hemoglobin, albumin, prealbumin, potassium, sodium, magnesium, and calcium were observed in these patients (p < 0.05). The prevalence of nutritional risk decreased over time during chemotherapy (p < 0.05). Nutritional parameters, including BMI, PNI, and the serum concentrations of albumin and prealbumin, exhibited an upward trend in nutritional status throughout the chemotherapy cycles (p < 0.05). Multivariate analysis indicated that higher levels of BMI, serum albumin, prealbumin, absolute lymphocyte count, and hemoglobin ≥ 110 g/L at admission were associated with elevated PNI after chemotherapy (ß = 0.077, p = 0.028; ß = 0.315, p < 0.001; ß = 0.009, p < 0.001; ß = 1.359, p < 0.001; ß = - 0.637, p = 0.005). CONCLUSION: Patients consistently demonstrated improvements in nutritional risk and status from the initiation to the completion of chemotherapy cycles. Nutritional monitoring of OC women, particularly those exhibiting abnormalities at the commencement of chemotherapy, is crucial. Targeted nutritional support programs should be developed to enhance the prognosis of OC women.

Nucleoside modification-based flexizymes with versatile activity for tRNA aminoacylation.

Extensive research has focused on genetic code reprogramming using flexizymes (Fxs), ribozymes enabling diverse tRNA acylation. Here we describe a nucleoside-modification strategy for the preparation of flexizyme variants derived from 2'-OMe, 2'-F, and 2'-MOE modifications with unique and versatile activities, enabling the charging of tRNAs with a broad range of substrates. This innovative strategy holds promise for synthetic biology applications, offering a robust pathway to expand the genetic code for diverse substrate incorporation.

Radioactive iodine therapy for follicular thyroid cancer: a 15 years follow-up study of Chinese patients.

PURPOSE: To identify long-term predictors of distant metastases (DM) and the overall survival (OS) of follicular thyroid cancer (FTC) patients who underwent radioactive iodine (RAI) therapy. And to expand the knowledge about the clinical course and experience of RAI treatment for FTC. MATERIALS: A total of 117 FTC patients who underwent RAI therapy at our institution from 2005 to 2020 were retrospectively studied. Patient characteristics, serum stimulating thyroglobulin (sTg) and thyroglobulin antibody levels, treatment process and follow-up data were collected until 26 April 2022. RESULTS: A total of 16 patients (13.7%) were lost to follow-up. A total of 23 (19.7%) patients with DM died and all FTC without DM were still alive. DM was seen in 58.4% (59/101) of patients. The most common location for metastatic lesions was the lung. Then was bone. The mean survival time of FTC with RAI was 156 months [95% confidence interval (CI): 142-171]. Five-year and 10-year cumulative survival rates of them were 88.8% and 67.4%, respectively. As for patients with DM were 80.4% and 41.3%, respectively. Age at diagnosis [odds ratio (OR) = 1.080, P  = 0.009], RAI therapy sessions (OR = 2.959, P  = 0.001) and sTg level (OR = 1.006, P  = 0.002) were predictive of DM occurrence in FTC with RAI. In the group of FTC with DM, survival analysis showed that males were more likely to have a lower OS than females ( P  = 0.039). CONCLUSION: Age, number of RAI therapy sessions, and sTg level were predictive of the occurrence of DM in FTC patients with RAI. Sex would influence the OS of FTC patients with DM.

Novel insight into cGAS-STING pathway in ischemic stroke: from pre- to post-disease.

Ischemic stroke, a primary cause of disability and the second leading cause of mortality, has emerged as an urgent public health issue. Growing evidence suggests that the Cyclic GMP-AMP synthase (cGAS)- Stimulator of interferon genes (STING) pathway, a component of innate immunity, is closely associated with microglia activation, neuroinflammation, and regulated cell death in ischemic stroke. However, the mechanisms underlying this pathway remain inadequately understood. This article comprehensively reviews the existing literature on the cGAS-STING pathway and its multifaceted relationship with ischemic stroke. Initially, it examines how various risk factors and pre-disease mechanisms such as metabolic dysfunction and senescence (e.g., hypertension, hyperglycemia, hyperlipidemia) affect the cGAS-STING pathway in relation to ischemic stroke. Subsequently, we explore in depth the potential pathophysiological relationship between this pathway and oxidative stress, endoplasmic reticulum stress, neuroinflammation as well as regulated cell death including ferroptosis and PANoptosis following cerebral ischemia injury. Finally, it suggests that intervention targeting the cGAS-STING pathway may serve as promising therapeutic strategies for addressing neuroinflammation associated with ischemic stroke. Taken together, this review concludes that targeting the microglia cGAS-STING pathway may shed light on the exploration of new therapeutic strategies against ischemic stroke.

Nerve Injury-Induced γH2AX Reduction in Primary Sensory Neurons Is Involved in Neuropathic Pain Processing.

Phosphorylation of the serine 139 of the histone variant H2AX (γH2AX) is a DNA damage marker that regulates DNA damage response and various diseases. However, whether γH2AX is involved in neuropathic pain is still unclear. We found the expression of γH2AX and H2AX decreased in mice dorsal root ganglion (DRG) after spared nerve injury (SNI). Ataxia telangiectasia mutated (ATM), which promotes γH2AX, was also down-regulated in DRG after peripheral nerve injury. ATM inhibitor KU55933 decreased the level of γH2AX in ND7/23 cells. The intrathecal injection of KU55933 down-regulated DRG γH2AX expression and significantly induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. The inhibition of ATM by siRNA could also decrease the pain threshold. The inhibition of dephosphorylation of γH2AX by protein phosphatase 2A (PP2A) siRNA partially suppressed the down-regulation of γH2AX after SNI and relieved pain behavior. Further exploration of the mechanism revealed that inhibiting ATM by KU55933 up-regulated extracellular-signal regulated kinase (ERK) phosphorylation and down-regulated potassium ion channel genes, such as potassium voltage-gated channel subfamily Q member 2 (Kcnq2) and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in vivo, and KU559333 enhanced sensory neuron excitability in vitro. These preliminary findings imply that the down-regulation of γH2AX may contribute to neuropathic pain.

Effect of a combination of Atractylodes macrocephala extract with strychnine on the TLR4/NF-κB/NLRP3 pathway in MH7A cells.

Rheumatoid arthritis (RA) is now widely recognized as a chronic systemic inflammatory autoimmune disease characterized by swelling, pain and stiffness, which are often disabling. Although the number of drugs available for the treatment of RA has increased in recent years, they are generally expensive, leave patients prone to relapse and can result in severe effects when discontinued. Thus, there is a need for an inexpensive drug with fewer side effects that can be adhered to relieve pain and slow down the progression of the disease. Strychnine, a traditional Chinese medicine, was often used in ancient times to treat swollen and painful joints; however, because of its somewhat toxic nature, it is often combined with Atractylodes macrocephala to reduce its toxicity for safer therapeutic action. The present study performed high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) analysis to confirm whether the use of strychnine with Atractylodes macrocephala had the effect of reducing strychnine content. MH7A cells were induced using IL-1ß to study the effect of strychnine with Atractylodes macrocephala on the Toll-like receptor 4 (TLR4)/NF-κB/NLR family pyrin domain-containing 3 (NLRP3) pathway in order to verify its role in the treatment of RA. The results indicated that the combined application of HPLC-MS/MS strychnine and Atractylodes macrocephala had a reducing effect on the strychnine content. From the subsequent experimental results, it can be inferred that Strychnine combined with Atractylodes macrocephala extract could promote the apoptosis of synovial cells, and could inhibit the expression levels of TLR4, NF-κB and NLRP3 in the cells as well as reducing the MH7A-positive cells. The expression levels of TLR4, IκB kinase ß, NF-κB and NLRP3 were significantly reduced after treatment with each administration group, resulting in a decrease in the phosphorylation levels of TLR4 and NF-κB, indicating that the combination potently inhibited their phosphorylation. The combination of strychnine and atractylenolide II was also revealed to be the main active ingredient in the treatment of RA.

Influence of Self-Perceived Burden on Quality of Life in Patients with Urostomy Based on Structural Equation Model: The Mediating Effects of Resilience and Social Support.

Objective: To investigate the current situation of self-perceived burden in patients with urostomy, analyze the correlation between self-perceived burden and quality of life, and explore the intermediary role of resilience and social support. Methods: The convenience sampling method was used to select 303 patients with urostomy of outpatient departments of the three tertiary hospitals in Yinchuan, Ningxia region, China, from April 1, 2020, to October 1, 2020, who then completed a survey questionnaire. The survey questionnaire contained a general data questionnaire and self-perceived burden scale, city of hope-quality of life-ostomy questionnaire, Connor-Davidson resilience scale, and social support rating scale. Results: Self-perceived burden was present among 89.8% patients with urostomy; the quality of life of patients with urostomy is low. The results showed that the self-perceived burden and quality of life, resilience, and social support are related in pairs; self-perceived burden was significantly negatively correlated with quality of life，resilience, and social support; there was a significant positive correlation between quality of life, resilience, and social support; resilience and social support were parallel mediators. Conclusions: Patients with urostomy had a heavy self-perceived burden and low quality of life. Reducing the self-perceived burden of patients with urostomy by improving the level of resilience and social support, could raise the level of quality of life. This study could provide empirical basis for nurses to take continuous nursing intervention measures in order to reduce the self-perceived burden of patients with urostomy and ultimately to improve the quality of life.

CT-guided radiofrequency ablation of the extracranial cranial nerve for the treatment of Meige's syndrome.

Background: Meige' s syndrome, a rare form of dystonia, lacks effective treatment. The purpose of this study was to determine the effects of CT-guided percutaneous extracranial radiofrequency ablation of the facial and/or trigeminal nerves in the treatment of Meige's syndrome. Methods: A total of 10 patients were enrolled in this study, with the numbers of blepharospasm dystonia syndrome (BDS), oromandibular dystonia syndrome (ODS), and blepharospasm combined with oromandibular dystonia syndrome (B-ODS) being 7, 1, and 2, respectively. BDS patients underwent radiofrequency ablation of the bilateral stylomastoid foramen facial nerve; ODS patients underwent radiofrequency ablation of the bilateral foramen oval trigeminal mandibular branch, and B-ODS patients underwent radiofrequency ablation of the bilateral stylomastoid foramen facial nerve and foramen oval trigeminal mandibular branch. The therapeutic effects and complications were observed. Results: All 10 patients in this series experienced improved Meige's syndrome-related symptoms after extracranial radiofrequency ablation of the cranial and/or mandibular branches of the extracranial trigeminal nerve. Adverse events included class II-III facial paralysis and/or mandibular skin numbness. Two patients had recurrences at the 18th and 22nd months postoperatively, respectively; the other patients were being followed up. Conclusion: These results shown that CT-guided radiofrequency ablation of bilateral stylomastoid foramen facial nerve and/or oval foramen trigeminal mandibular branch can effectively treat the corresponding types of Meige's syndrome. According to preliminary observations, the therapeutic effect may last more than 18 months.

A structural equation model-based study on the status and influencing factors of acute exacerbation readmission of elderly patients with chronic obstructive pulmonary disease within 30 days.

OBJECTIVE: To investigate the circumstances that lead to acute exacerbation readmission of elderly patients with chronic obstructive pulmonary disease (COPD) within 30 days and to explore the influencing factors of readmission using a structural equation model to provide evidence for medical staff so that effective intervention measures can be taken. METHODS: The convenience sampling method was used to select 1120 elderly patients with COPD from the respiratory departments of thirteen general hospitals in the Ningxia region, China, from April 2019 to August 2020, who then completed a survey questionnaire. The survey questionnaire contained a general data questionnaire and the modified Medical Research Council, activities of daily living, geriatric depression scale and COPD assessment test scales. RESULTS: The readmission rate of patients with COPD presenting with acute exacerbation within 30 days was determined to be 21.52%. Therefore, the modified model measures data accurately. The results showed that seasonal factors, family rehabilitation, age factors and overall health status were direct factors in the acute exacerbation readmission of patients with COPD within 30 days of hospital discharge. Smoking is not only a direct factor for acute exacerbation readmission within 30 days but also an indirect factor through disease status; disease status and chronic disease are not only direct factors for acute exacerbation readmission within 30 days but also indirect factors through the patient's overall health status. CONCLUSIONS: The rate of patients with COPD presenting with acute exacerbation within 30 days is high; while taking measures to prevent readmission based on influencing factors that directly impact admission rates, attention should also be paid to the interaction between these factors.

Identification of potential key molecules and signaling pathways for psoriasis based on weighted gene co-expression network analysis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, the pathogenesis of which is more complicated and often requires long-term treatment. In particular, moderate to severe psoriasis usually requires systemic treatment. Psoriasis is also associated with many diseases, such as cardiometabolic diseases, malignant tumors, infections, and mood disorders. Psoriasis can appear at any age, and lead to a substantial burden for individuals and society. At present, psoriasis is still a treatable, but incurable, disease. Previous studies have found that microRNAs (miRNAs) play an important regulatory role in the progression of various diseases. Currently, miRNAs studies in psoriasis and dermatology are relatively new. Therefore, the identification of key miRNAs in psoriasis is helpful to elucidate the molecular mechanism of psoriasis. AIM: To identify key molecular markers and signaling pathways to provide potential basis for the treatment and management of psoriasis. METHODS: The miRNA and mRNA data were obtained from the Gene Expression Omnibus database. Then, differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) were screened out by limma R package. Subsequently, DEmRNAs were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomics functional enrichment. The "WGCNA" R package was used to analyze the co-expression network of all miRNAs. In addition, we constructed miRNA-mRNA regulatory networks based on identified hub miRNAs. Finally, in vitro validation was performed. All experimental procedures were approved by the ethics committee of Chinese PLA General Hospital (S2021-012-01). RESULTS: A total of 639 DEmRNAs and 84 DEmiRNAs were identified. DEmRNAs screening criteria were adjusted P (adj. P) value < 0.01 and |logFoldChange| (|logFC|) > 1. DEmiRNAs screening criteria were adj. P value < 0.01 and |logFC| > 1.5. KEGG functional analysis demonstrated that DEmRNAs were significantly enriched in immune-related biological functions, for example, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, and chemokine signaling pathway. In weighted gene co-expression network analysis, turquoise module was the hub module. Moreover, 10 hub miRNAs were identified. Among these 10 hub miRNAs, only 8 hub miRNAs predicted the corresponding target mRNAs. 97 negatively regulated miRNA-mRNA pairs were involved in the miRNA-mRNA regulatory network, for example, hsa-miR-21-5p-claudin 8 (CLDN8), hsa-miR-30a-3p-interleukin-1B (IL-1B), and hsa-miR-181a-5p/hsa-miR-30c-2-3p-C-X-C motif chemokine ligand 9 (CXCL9). Real-time polymerase chain reaction results showed that IL-1B and CXCL9 were up-regulated and CLDN8 was down-regulated in psoriasis with statistically significant differences. CONCLUSION: The identification of potential key molecular markers and signaling pathways provides potential research directions for further understanding the molecular mechanisms of psoriasis. This may also provide new research ideas for the prevention and treatment of psoriasis in the future.

The Nursing Effect of PRECEDE Management on Occupational Exposure to Surgical Smoke: Based on a Randomized Controlled Study.

Background: Occupational exposure seriously threatens the physical and mental health of professionals and has become an important public health problem. In clinical medical and nursing work, medical staff, especially nursing staff, are faced with the status quo of occupational exposure with high risk, serious harm, and severe situation. Therefore, a sound management system must be established to control the occupational exposure of nurses. Aims: According to the PRECEDE management model, evaluate the operating room nurses' knowledge, belief, and behavior scores on the protection of surgical smoke, understand their awareness of surgical smoke and the current status of protection, improve the mastery rate and protection compliance of surgical smoke-related knowledge in the operating room, reduce the harm of surgical smoke to the human body, and provide a basis for smoke protection.Materials and methods. 125 doctors working in the operating room of our hospital were selected as the control group of this study, and 112 nonsmoke-exposed nurses working in the operating room of our hospital were selected as the observation group. The nurses' knowledge-belief behavior scores and self-evaluation scores of smoke influence were counted before and after the intervention in the operating room. SPSS25.0 was used to process the data. Tests and repeated measures analysis of variance were used to compare the effects before and after intervention. Results: After one month of intervention, the knowledge scores of nurses in the operating room on the protection of surgical smoke increased significantly, and the difference was significant (P < 0.05); the scores of related concepts, physical properties, chemical properties, and authoritative protection standards increased significantly (P < 0.05). There was no significant increase in the scores of smoke hazards (P > 0.05); the attitude of smoke protection increased significantly, which was statistically significant (P < 0.05); and the behavior compliance of smoke protection was significantly increased, which was statistically significant (P < 0.05). After one month of intervention, the self-evaluation score of smoke effect of operating room nurses decreased significantly, and the difference was statistically significant (P < 0.05). The data was analyzed by repeated measure analysis of variance. The knowledge of surgical smoke (F = 65.570, P < 0.001), attitude (F = 78.307, P < 0.001), and behavior (F = 403.015, P < 0.001) scores gradually increased. The observation group's total cholesterol, low-density lipoprotein cholesterol, and the proportion of low-density lipoprotein cholesterol were higher than that of the control group, and the proportion of high-density lipoprotein cholesterol was lower than that of the control group. The difference was statistically significant P < 0.05. Conclusion: After the intervention of operating room nurses under the guidance of PRECEDE management mode, the theoretical knowledge of operating room nurses is effectively improved, the operations are standardized, the self-evaluation scores of smoke influence are reduced, and the safety level of operating room is improved. More importantly, the health of nursing staff is fully guaranteed.

The delivery of miR-21a-5p by extracellular vesicles induces microglial polarization via the STAT3 pathway following hypoxia-ischemia in neonatal mice.

Extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs) have previously been shown to protect against brain injury caused by hypoxia-ischemia (HI). The neuroprotective effects have been found to relate to the anti-inflammatory effects of EVs. However, the underlying mechanisms have not previously been determined. In this study, we induced oxygen-glucose deprivation in BV-2 cells (a microglia cell line), which mimics HI in vitro, and found that treatment with MSCs-EVs increased the cell viability. The treatment was also found to reduce the expression of pro-inflammatory cytokines, induce the polarization of microglia towards the M2 phenotype, and suppress the phosphorylation of selective signal transducer and activator of transcription 3 (STAT3) in the microglia. These results were also obtained in vivo using neonatal mice with induced HI. We investigated the potential role of miR-21a-5p in mediating these effects, as it is the most highly expressed miRNA in MSCs-EVs and interacts with the STAT3 pathway. We found that treatment with MSCs-EVs increased the levels of miR-21a-5p in BV-2 cells, which had been lowered following oxygen-glucose deprivation. When the level of miR-21a-5p in the MSCs-EVs was reduced, the effects on microglial polarization and STAT3 phosphorylation were reduced, for both the in vitro and in vivo HI models. These results indicate that MSCs-EVs attenuate HI brain injury in neonatal mice by shuttling miR-21a-5p, which induces microglial M2 polarization by targeting STAT3.

Use of transcutaneous electrical acupoint stimulation in pulmonary surgery for patients with tuberculosis.

Objective: This study aimed to analyze the effects of transcutaneous electrical acupoint stimulation (TEAS) on the immune function in patients with pulmonary tuberculosis (PT) and the inflammatory response following one-lung ventilation surgery by comparing the levels of inflammatory mediators, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 8 (IL-8); T lymphocyte subsets, including CD3+, CD4+, CD8+, and CD4+/CD8+ cells; and natural killer cells (NK cells). Methods: We randomly divided 62 patients who underwent general anesthesia for thoracotomy into two groups: TEAS and sham TEAS. Patients in the TEAS group underwent bilateral acupoint electrical stimulation at the Hou-Xi, Zhi-Gou, Nei-Guan, and He-Gu acupoints from 30 min before anesthesia induction until the end of surgery. TEAS was continuously maintained throughout the procedure with a dilatational wave at 2/100 Hz. Those in the sham TEAS group underwent the same management but without stimulation, and the anesthesia induction and maintenance methods were the same in both groups. Venous blood was drawn to monitor inflammatory mediators and lymphocyte subsets before anesthesia induction and 5 days after the surgery. Results: There was no statistical difference in the general conditions between the two groups (P > 0.05). Before anesthesia induction, the levels of inflammatory factors (IL-6, IL-8, and TNF-α), lymphocyte subsets (CD3+, CD4+, and CD4+/CD8+), and NK cells did not statistically differ between the two groups (P > 0.05). Compared to the sham TEAS group, the levels of IL-6, IL-8, TNF-α, and CD8+ were lower in the TEAS group, while those of CD3+, CD4+, CD4+/CD8+, and NK cells were higher; however, only the change in TNF-α was significant (P < 0.05). Conclusion: TEAS at the Hou-Xi, Zhi-Gou, Nei-Guan, and He-Gu acupoints at 2 Hz/100 Hz can reduce the inflammatory response during one-lung ventilation but has no significant effect on the immune function in patients with tuberculosis.

L-Cysteine attenuates osteopontin-mediated neuroinflammation following hypoxia-ischemia insult in neonatal mice by inducing S-sulfhydration of Stat3.

We previously show that L-Cysteine administration significantly suppresses hypoxia-ischemia (HI)-induced neuroinflammation in neonatal mice through releasing H2S. In this study we conducted proteomics analysis to explore the potential biomarkers or molecular therapeutic targets associated with anti-inflammatory effect of L-Cysteine in neonatal mice following HI insult. HI brain injury was induced in postnatal day 7 (P7) neonatal mice. The pups were administered L-Cysteine (5 mg/kg) at 24, 48, and 72 h post-HI. By conducting TMT-based proteomics analysis, we confirmed that osteopontin (OPN) was the most upregulated protein in ipsilateral cortex 72 h following HI insult. Moreover, OPN was expressed in CD11b+/CD45low cells and infiltrating CD11b+/CD45high cells after HI exposure. Intracerebroventricular injection of OPN antibody blocked OPN expression, significantly attenuated brain damage, reduced pro-inflammatory cytokine levels and suppressed cerebral recruitment of CD11b+/CD45high immune cells following HI insult. L-Cysteine administration reduced OPN expression in CD11b+/CD45high immune cells, concomitant with improving the behavior in Y-maze test and suppressing cerebral recruitment of CD11b+/CD45high immune cells post-HI insult. Moreover, L-Cysteine administration suppressed the Stat3 activation by inducing S-sulfhydration of Stat3. Intracerebroventricular injection of Stat3 siRNA not only decreased OPN expression, but also reversed HI brain damage. Our data demonstrate that L-Cysteine administration effectively attenuates the OPN-mediated neuroinflammation by inducing S-sulfhydration of Stat3, which contributes to its anti-inflammatory effect following HI insult in neonatal mice. Blocking OPN expression may serve as a new target for therapeutic intervention for perinatal HI brain injury.

Pharmacodynamic Evaluation of the Gexia Zhuyu Decoction in the Treatment of NAFLD and the Molecular Mechanism Underlying the TRPM4 Pathway Regulation.

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome of abnormal lipid deposition in the liver mediated by nonalcohol intake. The Gexia Zhuyu decoction, a classic traditional Chinese medicine compound, is widely used in the clinical treatment of NAFLD. However, its specific efficacy and underlying mechanisms have not been elucidated yet. This study aimed to quantitatively evaluate the efficacy of the Gexia Zhuyu decoction using pharmacodynamics and to explore its molecular mechanisms in conjunction with proteomics. High-fat diets and methionine choline-deficient diets were used to induce various NAFLD progression stages in mouse models. The effects of oral Gexia Zhuyu decoction administration on NAFLD were evaluated by measuring the serum and liver indicators of the treated mice before and after drug intervention and by comparing the changes in liver tissue. Liver TRPM4 mRNA and protein levels were measured using reverse transcription-polymerase chain reaction and Western blotting, respectively. Experimental data showed that serum ALT, AST, and liver triglyceride (TG) levels in each disease stage group of drug intervention mice decreased, and high-density lipoprotein (HDL) and superoxide dismutase (SOD) levels increased. Liver TG levels decreased after drug intervention in the liver fibrosis mice, but serum TG levels increased. Furthermore, cellular fatty changes, inflammatory changes, and fibrous tissue proliferation were all relieved. The TRPM4 protein and mRNA levels in the liver tissue were decreased, and the microRNA (miRNA)-24 expression was increased. The Gexia Zhuyu decoction has a clear therapeutic effect at each stage of NAFLD. It likely acts by altering miRNA-24 expression and regulating the target TRPM4 protein pathway to achieve NAFLD treatment.

[Textual research of Schizonepetae Herba and Schizonepetae Spica].

Schizonepetae Herba and Schizonepetae Spica are well-known Chinese herbal medicines for wind dispersing and exterior releasing. Through textual research on Schizonepetae Herba and Schizonepetae Spica, the discrimination of their medicinal parts in history was clarified, and the processing, the property(nature and flavor), meridian tropism, functions, indications, usage, dosage, and the selection of decoction pieces were compared to provide the basis for clinical application. As a result, the whole herb of Schizonepeta tenuifolia was used as medicine in the early records. The aerial part and the dried spike of S. tenuifolia were used as medicines separately in the Song Dynasty, which was recorded in the Atlas of Materia Medica(Ben Cao Tu Jing). Some ancient classics emphasized that only the dried spike could be used as medicine. The separation of Schizonepetae Herba and Schizonepetae Spica meets the different needs of clinical medication and supports the concept of rational development and utilization of Chinese medicine resources. About ten processing methods for Schizonepetae Herba and Schizonepetae Spica have been recorded since ancient times, and raw and charred drugs were the major products. Raw Schizonepetae Herba is required to be used in sections, whereas raw Schizonepetae Spica in clean preparation. Both charred products should avoid scorching. Schizonepetae Herba and Schizonepetae Spica are similar in the property(pungent, bitter, and warm), meridian tropism(lung and liver meridians, as well as qi and blood aspects), and functions(releasing exterior, dispersing wind, regulating and stopping blood, promoting eruption, dispelling sores, promoting digestion, eliminating alcohol effect, etc.), but Schizonepetae Spica is superior in efficacy. For Schizonepetae Herba and Schizonepetae Spica in traditional Chinese medicinal prescriptions, the raw and charred products are similar in usage and dosage, while their focuses in clinical compatibility vary. The raw and charred products of Schizonepetae Herba and Schizonepetae Spica are widely applied clinically. Decoction pieces of different specifications can result in different efficacies and clinical applications, so medication should be performed with caution.

[The Effect of Novel Phosphodiesterase 4 Inhibitor ZL-n-91 to the Proliferation of Leukemia Cells].

OBJECTIVE: To investigate the inhibitory effects of novel phosphodiesterase 4 inhibitor ZL-n-91 to the proliferation of leukemia cells L1210 and K562. METHODS: CCK-8 method was used to detect the effect of ZL-n-91 to the proliferation of L1210 and K562 cells, and the proliferation rate, IC50 were calculated. The effects of ZL-n-91 to the cycle of L1210 and K562 cells was detected by PE single staining, and the effects of ZL-n-91 to the apoptosis of L1210 and K562 cells was detected by PE/7AA-D double staining. Western blot was used to detect the effect of ZL-n-91 to the expression levels of apoptosis related proteins. Subcutaneous tumor transplantation model of acute lymphoblastic leukemia L1210 was established in the nude mice, and the inhibitory effect of oral administration of ZL-n-91 to the xenograft was observed. RESULTS: ZL-n-91 showed a significant inhibitory effect to the proliferation of leukemia cells L1210 and K562 in a dose-dependent manner (P<0.001). After treated by ZL-n-91, the leukemia cells L1210 and K562 in the S-phase in cell cycle decreased significantly compared with those in control group (P<0.01). The apoptosis of leukemia cells L1210 and K562 could be induced by ZL-n-91 (P<0.001), and the expression level of apoptosis related protein BAX significantly increased. In the animal experiment, the result showed that ZL-n-91 could significantly inhibit the growth of subcutaneously transplantation tumor (P<0.05). CONCLUSION: The novel phosphodiesterase 4 inhibitor ZL-n-91 can effectively inhibit the proliferation of leukemia cells L1210 and K562, which has the potential of anti-leukemia drug development.

A Retrospective Study of Biliary Drainage Strategies for Patients with Malignant Hilar Biliary Strictures.

PURPOSE: The main aim of this study was to compare the efficacy and safety of different biliary drainage strategies, including percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary stenting (EBS) and unilateral versus bilateral stenting, in patients with unresectable malignant hilar biliary strictures (MHBSs). PATIENTS AND METHODS: This was a retrospective review of patients with inoperable MHBSs who underwent biliary drainage by either EBS or PTBD. Efficacy and safety were compared between the two pathways and between unilateral and bilateral stenting in the EBS group. The survival duration was analyzed with K-M curves and Log rank tests. RESULTS: From January 2015 to December 2019, a total of 206 (126: EBS and 80: PTBD) patients with MHBSs were enrolled in our study and underwent 270 procedures (173: EBS and 97: PTBD). Bilateral stenting was superior to unilateral stenting in terms of clinical success (69.6% vs 50.6%, p=0.039), especially for patients with Bismuth type IV (70.0% vs 30.3%, p=0.002). A higher decrease in bilirubin was seen with PTBD in patients with Bismuth types III-IV (66.9 vs 36.7, p=0.006). A survival advantage was seen in successful drainage (227 days vs 82 days, p<0.001), lower tumor-node-metastasis (TNM) scores (I-II) (195 days vs 139 days, p=0.012), and cholangiocarcinoma (184 days vs 84 days, p=0.001). CONCLUSION: For patients with advanced MHBSs, bilateral stenting may achieve a better drainage effect than unilateral stenting, and PTBD may have a better performance in relieving cholestasis than EBS. Successful drainage and cholangiocarcinoma may provide greater long-term survival benefits.