The safety of benzodiazepines and related drugs during pregnancy: an updated meta-analysis of cohort studies.

PURPOSE: The prevalence of benzodiazepines and related drugs (BZRDs) use during pregnancy increased sharply in recent years. Thus, there are concerns regarding the pregnancy outcomes following exposure to BZRDs. METHODS: Two electronic databases were thoroughly searched to identify related clinical studies published from inception until June 2023. English-language cohort studies with high-quality comparing antenatal BZRDs exposure to an unexposed group on any delivery outcome were included. RESULTS: Ten cohort studies that estimated adverse neonatal outcomes associated with exposure to BZRDs during pregnancy were included. Exposure to BZRDs during pregnancy was associated with an increased risk of congenital malformation [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.05-1.13, p < 0.001], heart malformation (OR 1.13, 95% CI 1.04-1.22, p = 0.003), preterm birth (OR 1.45, 95% CI 1.23-1.7, p < 0.001), SGA (OR 1.18, 95% CI 1.08-1.29, P < 0.001), LBW (OR 1.42, 95% CI 1.25-1.6, p = 0.001) or low Apgar score (OR 1.42, 95% CI 1.08-1.87, p = 0.011),compared with no exposure. Further analyses limited to the first trimester exposure yielded consistent results. CONCLUSIONS: Exposure to BZRDs during pregnancy may be associated with several adverse neonatal outcomes. However, we could not rule out the potential indication confounding factor, further studies with high-quality that control for important confounders are still needed to verify our findings.

Improving ocular bioavailability of hydrophilic drugs through dynamic covalent complexation.

The clinical benefits of diquafosol tetrasodium (DQS), a hydrophilic P2Y2 receptor agonist for dry eye, have been hindered by a demanding dosing regimen. Nevertheless, it is challenging to achieve sustained release of DQS with conventional drug delivery vehicles which are mainly designed for hydrophobic small molecule drugs. To address this, we developed an affinity hydrogel for DQS by taking advantage of borate-mediated dynamic covalent complexation between DQS and hydroxypropyl guar. The resultant formulation (3% DQS Gel) was characterized by sustained release, low corneal permeation, and extended ocular retention, which were desirable attributes for ocular surface drug delivery. Both in vitro and in vivo studies had been carried out to verify the biocompatibility of 3% DQS Gel. Using corneal fluorescein staining, the Schirmer's test, PAS staining, quantitative PCR and immunohistological analyses as outcome measures, the superior therapeutic effects of 3% DQS Gel over PBS, the hydrogel vehicle and free DQS were demonstrated in a mouse dry eye model. Our DQS delivery strategy reported herein is readily applicable to other hydrophilic small molecule drugs with cis-diol moieties, thus providing a general solution to improve clinical outcomes of numerous diseases.

Easily misdiagnosed complex Klippel-Trenaunay syndrome: A case report.

BACKGROUND: Klippel-Trenaunay syndrome (KTS) is a congenital vascular malformation with a complicated etiology. It is sporadic and clinically rare in occurrence. The typical characteristics are capillary malformation (also known as port-wine stain), varicose veins and malformations, and bony and/or soft tissue hypertrophy with or without lymphatic malformation, which are known as the "classic clinical triad". Herein, a rare case of KTS characterized by crossed-bilateral limb hypertrophy accompanied by intermittent hematochezia and hematuria is reported. CASE SUMMARY: We described a 37-year-old female with KTS. She was admitted to our hospital owing to the gradual enlargement of the left lower extremity along with intermittent hematochezia and hematuria. The patient was diagnosed to have hemorrhoid bleeding by other hospitals and treated with conventional hemostatic drugs, but continued to have intermittent gastrointestinal bleeding and hematuria. Therefore, she visited our hospital to seek further treatment. During hospitalization, relevant imaging and laboratory examinations and colonoscopy were performed. In combination with the patient's history and relevant examinations, we considered that the patient had a complex form of KTS. We recommended a combined diagnosis and treatment from the vascular, interventional, anorectal, and other departments, although she declined any further treatment for financial reasons. CONCLUSION: The clinical manifestations of KTS are extensive and diverse and chiefly include the typical triad. However, Vascular malformations of KTS can also involve several parts and systems such as digestive and urogenital systems. Therefore, the atypical manifestations and rare complications necessitate the clinician's attention and are not to be ignored.

[First-Class Nursing Discipline Construction Spearheads the Cultivation of First-Class Talents].

Cultivating first-class talents is a key task of the Double First-Class Initiative, a national plan to build a number of world-class universities and disciplines in China by the end of 2050. On the basis of reviewing the history of the development of the nursing discipline, we analyzed, herein, opportunities and challenges of nursing professional training under the strategic guidance of the Double First-Class Initiative. We proposed suggestions on the cultivation of first-class nursing professionals of the future by considering the following aspects, constructing a theoretical system of ideological and political education for nursing education with Chinese characteristics, exploring for ways to develop a nursing knowledge system and personnel training model around the axis of a life-course approach to health, building "nursing plus" interdisciplinary clusters to cultivate innovative talents with interdisciplinary integrated abilities, enhancing efforts to recruit and cultivate scientific and technological talents, optimizing in an all-round way the composition of qualified nursing personnel, gaining the support of first-class research platforms, and creating incubation centers for innovative and outstanding nursing professionals.

Synchronous early gastric and intestinal mucosa-associated lymphoid tissue lymphoma in a Helicobacter pylori-negative patient: A case report.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma occurs largely in the digestive tract, with the stomach being the most commonly affected organ, followed by the small intestine, large intestine, and esophagus. It is rarely found in both the stomach and colon. Helicobacter pylori (H. pylori) infection is strongly associated with gastric MALT lymphoma, although there is a small number of H. pylori-negative gastric MALT lymphomas. Diagnosis of MALT lymphoma is challenging because of nonspecific symptoms and diverse presentations of endoscopic findings. CASE SUMMARY: We report a case of an asymptomatic patient who during screening endoscopy and was found to have stromal tumor-like submucosal uplift lesions in the stomach body and polypoid lesions in the rectum. After endoscopic resection, the patient was diagnosed with multiple early simultaneous gastrointestinal MALT lymphomas. CONCLUSION: This study may help improve our understanding of MALT lymphomas and multifocal lesions treated using early endoscopy.

Expression of hepatocyte nuclear factor 4 alpha, wingless-related integration site, and ß-catenin in clinical gastric cancer.

BACKGROUND: Gastric cancer (GC) is the second most common cause of cancer-related deaths worldwide. Hepatocyte nuclear factor 4 alpha (HNF4α) that belongs to the nuclear hormone receptor superfamily, is overexpressed in GC tissues, and might be involved in the development of GC by regulating its downstream wingless-related integration site (WNT)/ß-catenin signaling. AIM: To clarify the expression of HNF4α/WNT5a/ß-catenin signaling proteins in clinical GC tissues. METHODS: We immunohistochemically stained pathological blocks of GC and matched para-cancerous tissues. The intensity of HNF4α, WNT5a and ß-catenin staining in the tumor cells was determined according to cell rates and staining intensity. The correlations between GC and HNF4α, WNT5a, and ß-catenin expression using chi-square and paired chi-square tests. Relationships between double-positive HNF4α and WNT5a expression and types of gastric tumor tissues were assessed using regression analysis. Correlations between HNF4α and WNT5a expression at the RNA level in GC tissues found in the TCGA database were analyzed using Pearson correlation coefficients. RESULTS: We found more abundant HNF4α and WNT5a proteins in GC, especially in mucinous adenocarcinoma and mixed GC than in adjacent tissues (P < 0.001). Low and high levels of cytoplasmic ß-catenin respectively expressed in GC and adjacent tissues (P < 0.001) were not significantly associated with pathological parameters. CONCLUSION: The expressions of HNF4α and WNT5a could serve as early diagnostic biomarkers for GC.

Berberine retarded the growth of gastric cancer xenograft tumors by targeting hepatocyte nuclear factor 4α.

BACKGROUND: Gastric cancer is the third deadliest cancer in the world and ranks second in incidence and mortality of cancers in China. Despite advances in prevention, diagnosis, and therapy, the absolute number of cases is increasing every year due to aging and the growth of high-risk populations, and gastric cancer is still a leading cause of cancer-related death. Gastric cancer is a consequence of the complex interaction of microbial agents, with environmental and host factors, resulting in the dysregulation of multiple oncogenic and tumor-suppressing signaling pathways. Global efforts have been made to investigate in detail the genomic and epigenomic heterogeneity of this disease, resulting in the identification of new specific and sensitive predictive and prognostic biomarkers. Trastuzumab, a monoclonal antibody against the HER2 receptor, is approved in the first-line treatment of patients with HER2+ tumors, which accounts for 13%-23% of the gastric cancer population. Ramucirumab, a monoclonal antibody against VEGFR2, is currently recommended in patients progressing after first-line treatment. Several clinical trials have also tested novel agents for advanced gastric cancer but mostly with disappointing results, such as anti-EGFR and anti-MET monoclonal antibodies. Therefore, it is still of great significance to screen specific molecular targets for gastric cancer and drugs directed against the molecular targets. AIM: To investigate the effect and mechanism of berberine against tumor growth in gastric cancer xenograft models and to explore the role of hepatocyte nuclear factor 4α (HNF4α)-WNT5a/ß-catenin pathways played in the antitumor effects of berberine. METHODS: MGC803 and SGC7901 subcutaneous xenograft models were established. The control group was intragastrically administrated with normal saline, and the berberine group was administrated intragastrically with 100 mg/kg/d berberine. The body weight of nude mice during the experiment was measured to assess whether berberine has any adverse reaction. The volume of subcutaneous tumors during this experiment was recorded to evaluate the inhibitory effect of berberine on the growth of MGC803 and SGC7901 subcutaneous transplantation tumors. Polymerase chain reaction assays were conducted to evaluate the alteration of transcriptional expression of HNF4α, WNT5a and ß-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models. Western blotting and IHC were performed to assess the protein expression of HNF4α, WNT5a and ß-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models. RESULTS: In the both MGC803 and SGC7901 xenograft tumor models, berberine significantly reduced tumor volume and weight and thus retarded the growth rate of tumors. In the SGC7901 and MGC803 subcutaneously transplanted tumor models, berberine down-regulated the expression of HNF4α, WNT5a and ß-catenin in tumor tissues from both transcription and protein levels. Besides, berberine also suppressed the protein expression of HNF4α, WNT5a and ß-catenin in liver tissues. CONCLUSION: Berberine retarded the growth of MGC803 and SGC7901 xenograft model tumors, and the mechanism behind these anti-growth effects might be the downregulation of the expression of HNF4α-WNT5a/ß-catenin signaling pathways both in tumor tissues and liver tissues of the xenograft models.

Effects of Molecular Structure on Organic Contaminants' Degradation Efficiency and Dominant ROS in the Advanced Oxidation Process with Multiple ROS.

In this study, the previously overlooked effects of contaminants' molecular structure on their degradation efficiencies and dominant reactive oxygen species (ROS) in advanced oxidation processes (AOPs) are investigated with a peroxymonosulfate (PMS) activation system selected as the typical AOP system. Averagely, degradation efficiencies of 19 contaminants are discrepant in the CoCaAl-LDO/PMS system with production of SO4•-, •OH, and 1O2. Density functional theory calculations indicated that compounds with high EHOMO, low-energy gap (ΔE = ELUMO - EHOMO), and low vertical ionization potential are more vulnerable to be attacked. Further analysis disclosed that the dominant ROS was the same one when treating similar types of contaminants, namely SO4•-, 1O2, 1O2, and •OH for the degradation of CBZ-like compounds, SAs, bisphenol, and triazine compounds, respectively. This phenomenon may be caused by the contaminants' structures especially the commonly shared or basic parent structures which can affect their effective reaction time and second-order rate constants with ROS, thus influencing the contribution of each ROS during its degradation. Overall, the new insights gained in this study provide a basis for designing more effective AOPs to improve their practical application in wastewater treatment.

Efficient activation of PAA by FeS for fast removal of pharmaceuticals: The dual role of sulfur species in regulating the reactive oxidized species.

As peracetic acid (PAA) is being increasingly used as an alternative disinfectant, efficient activation of PAA by low-cost and environmentally friendly catalysts over a wide pH range is potentially useful for simultaneous sterilization and pharmaceutical degradation in wastewater, such as hospital wastewater. In this study, peracetic acid (PAA) was successfully activated by low-cost and environmental-friendly FeS (25 mg/L) for efficient oxidative removal of three pharmaceuticals over a wide pH range (3.0∼9.0) as indicated by 80∼100% removal rate within 5 min. As expected, Fe(II) rather than sulfur species was the primary reactive site for PAA activation, while unlike the homogeneous Fe2+/PAA system with organic radicals (R-O·) and ·OH as the dominant reactive oxidized species (ROS), ·OH is the key reactive species in the FeS/PAA system. Interestingly and surprisingly, in-depth investigation revealed the dual role of sulfur species in regulating the reactive oxidized species: (1) S(-II) and its conversion product H2S (aq) played a significant role in Fe(II) regeneration with a result of accelerated PAA activation; (2) however, the R-O· generated in the initial seconds of the FeS/PAA process was supposed to be quickly consumed by sulfur species, resulting in ·OH as the dominant ROS over the whole process. The selective reaction of sulfur species with R-O· instead of ·OH was supported by the obviously lower Gibbs free energy of CH3COO· and sulfur species than ·OH, suggesting the preference of CH3COO· to react with sulfur species with electron transfer. After treatment with the FeS/PAA system, the products obtained from the three pharmaceuticals were detoxified and even facilitated the growth of E. coli probably due to the supply of numerous carbon sources by activated PAA. This study significantly advances the understanding of the reaction between PAA and sulfur-containing catalysts and suggests the practical application potential of the FeS/PAA process combined with biotreatment processes.

Captopril related kidney damage: renal afferent arteriolar responses to angiotensin II and inflammatory signaling.

Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H2O2 and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-ß (TGF-ß) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT1R) and AT2R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-ß and COX-2, decreased production of H2O2 and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H2O2. The mRNAs of renal microvascular AT1R and AT2R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.

PLGA/ß-TCP composite scaffold incorporating cucurbitacin B promotes bone regeneration by inducing angiogenesis.

OBJECTIVES: Vascularization is an essential step in successful bone tissue engineering. The induction of angiogenesis in bone tissue engineering can be enhanced through the delivery of therapeutic agents that stimulate vessel and bone formation. In this study, we show that cucurbitacin B (CuB), a tetracyclic terpene derived from Cucurbitaceae family plants, facilitates the induction of angiogenesis in vitro. METHODS: We incorporated CuB into a biodegradable poly (lactide-co-glycolide) (PLGA) and ß-tricalcium phosphate (ß-TCP) biomaterial scaffold (PT/CuB) Using 3D low-temperature rapid prototyping (LT-RP) technology. A rat skull defect model was used to verify whether the drug-incorporated scaffold has the effects of angiogenesis and osteogenesis in vivo for the regeneration of bone defect. Cytotoxicity assay was performed to determine the safe dose range of the CuB. Tube formation assay and western blot assay were used to analyze the angiogenesis effect of CuB. RESULTS: PT/CuB scaffold possessed well-designed bio-mimic structure and improved mechanical properties. CuB was linear release from the composite scaffold without affecting pH value. The results demonstrated that the PT/CuB scaffold significantly enhanced neovascularization and bone regeneration in a rat critical size calvarial defect model compared to the scaffold implants without CuB. Furthermore, CuB stimulated angiogenic signaling via up-regulating VEGFR2 and VEGFR-related signaling pathways. CONCLUSION: CuB can serve as promising candidate compound for promoting neovascularization and osteogenesis, especially in tissue engineering for repair of bone defects. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study highlights the potential use of CuB as a therapeutic agent and strongly support its adoption as a component of composite scaffolds for tissue-engineering of bone repair.

Evaluation of sleep disorder in orthopedic trauma patients: a retrospective analysis of 1129 cases.

BACKGROUND: In the trauma center wards, it is not unusual for patients to have sleep disorders, especially patients with an acute injury. Meanwhile, there is substantial evidence that sleep disorder is a predictor of depression and is an important feature of posttraumatic stress disorder. METHODS: All orthopedic trauma patients confined in a trauma ward in West China Hospital of Sichuan University between April 2018 and July 2019 were included in this retrospective study. Patients with mental impairment or craniocerebral injuries were excluded from the study. Basic demographic data and the Injury Severity Score (ISS) classification based on medical records were collected. The Pittsburgh sleep quality index (PSQI) was used to evaluate sleep quality, the visual analog scale (VAS) was used to evaluate physical pain, and the Barthel Index (BI) was used to evaluate activities of daily living (ADL). Univariate linear regression analysis and multivariate linear regression analysis were used to identify independently related factors. RESULTS: The average PSQI score was 6.3 (± 4.0). A total of 581 (51.4%) patients had a PSQI score > 5, indicating the presence of sleep disorders. The PSQI score was > 10 in 174 (15.4%) patients. Univariate statistical analysis showed that age, sex, education, ADL, and ISS classification were associated with increased PSQI scores. Marital status and pain were not associated with increased PSQI scores. When we used multivariate analysis to control for confounding variables, sex, ADL, and ISS classification remained independently associated with PSQI (P = 0.002, < 0.000, and 0.002, respectively). CONCLUSIONS: In our study, sleep disorders were common (51.4% with PSQI > 5) and serious (15.4% with PSQI > 10) in patients with traumatic orthopedic injury. The following factors were closely associated with sleep disorders: sex, ADL, and ISS classification. Moreover, age and educational attainment have an independent impact on sleep quality. Unexpectedly, the VAS score for pain was not independently associated with the seriousness of sleep quality, which may be related to preemptive and multimodal analgesia. Further studies are required to clarify this ambiguity.

Mechanical Insights into Thiol-Mediated Synergetic Biotransformation of Cadmium and Selenium in Nematodes.

Cadmium ion (Cd2+) is a common environmental pollutant with high biotoxicity. Interestingly, the Cd2+ biotoxicity can be alleviated by the coexisting selenite (SeO32-), which induces the formation of cadmium selenide-rich nanoparticles (CdSe NPs) under the function of thiol-capping peptides. However, the detailed biochemical mechanisms by which Cd and Se are synergistically transformed into CdSe NPs in living organisms remain unclear so far. Here, we shed light on the molecular basis of such biotransformation processes in Caenorhabditis elegans by focusing on the roles of several key thiol-capping peptides. By monitoring the compositional and structural changes of the Cd and Se species and the genetic-level responses of nematodes, we revealed the specific roles of glutathione (GSH) and phytochelatins (PCs) in mediating the CdSe NP formation. With the aid of in vitro bioassembly assay and density functional theory calculations, the detailed Cd-Se interaction pathways were further deciphered: the ingested Cd binds predominantly to GSH and PCs in sequence, then further interacts with selenocysteine to form tetrahedral-structured PC2-Cd2-Sec2 complex, and ultimately grows into CdSe NPs. This work provides molecular-level insights into the Cd-Se interaction in C. elegans and lays a basis for controlling the ecological and health risks of heavy metals in polluted environment.

Intracellular Hybrid Biosystem in a Protozoan to Trigger Visible-Light-Driven Photocatalysis.

Incorporating artificial photosensitizers with microorganisms has recently been recognized as an effective way to convert light energy into chemical energy. However, the incorporated biosystem is usually constructed in an extracellular manner and is vulnerable to the external environment. Here, we develop an intracellular hybrid biosystem in a higher organism protozoa Tetrahymena pyriformis, in which the in vivo synthesized CdS nanoparticles trigger photoreduction of nitrobenzene into aniline under visible-light irradiation. Integrating a photosensitizer CdS into T. pyriformis enables the photosensitizer CdS, inherent nitroreductase, and the cytoplasmic reductive substance in T. pyriformis to synergistically engage in the photocatalysis process, generating a greatly enhanced aniline yield with a 40-fold increment. Moreover, building an intracellular hybrid biosystem in mutant T. pyriformis could even grant it new capability of reducing nitrobenzene into aniline under visible-light irradiation. Such an intracellular hybrid biosystem paves a new way to functionalize higher organisms and diversify light energy conversion.

[Effect of acupoint thread-embedding on macrophage polarization of epididymis adipose tissue in obese mice].

OBJECTIVE: To observe the effect of acupoint thread-embedding at "Zusanli" (ST 36) and "Fenglong" (ST 40) on the macrophage polarization of epididymis adipose tissue in obese mice, and to explore the action mechanism of acupoint thread-embedding on weight control. METHODS: Among 30 male C57BL/6 mice, 10 mice were randomly selected and fed with normal diet, and the remaining 20 mice were fed with high-fat diet to establish the obesity model. Sixteen mice with successful obesity model were randomly divided into a model group and an acupoint thread-embedding group, 8 mice in each group. Eight mice were selected from mice which were fed with normal diet as the normal group. On the next day of successful modeling, acupoint thread-embedding was performed at "Zusanli" (ST 36) and "Fenglong" (ST 40) in the acupoint thread-embedding group, once every 10 days for 4 times. The body weight was recorded at 0, 8, 16, 24, 32, 40 days into intervention; the level of glucose metabolism was compared after intervention; the level of lipid metabolism and weight of epididymal adipose tissue were compared at the end of the intervention; the mRNA expression of M1 and M2 macrophage-related cytokines interleukin-10 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were detected by real-time PCR; the mRNA and protein expression of M1 macrophage labeled inducible nitric oxide synthase (iNOS) and M2 macrophage labeled arginase-1 (Arg-1) were detected by real-time PCR and Western blot. RESULTS: Compared with the normal group, the body weight at 0, 8, 16, 24, 32, 40 days into intervention in the model group was increased (P<0.05); the results of glucose tolerance test at 0, 30, 60, 120 min and insulin tolerance test at 0, 30, 60, 90, 120 min in the model group were higher than those in the normal group (P<0.05); the levels of total cholesterol and triacylglycerol in the model group were significantly higher than those in the normal group (P<0.001, P<0.01); the weight of epididymal adipose tissue in the model group was significantly higher than that in the normal group (P<0.001); the mRNA expression of IL-6, MCP-1, TNF-α and iNOS was increased (P<0.05, P<0.01, P<0.001), that of IL-10, Arg-1 was decreased (P<0.01), the protein expression of iNOS was up-regulated (P<0.01), and that of Arg-1 was down-regulated (P<0.001). Compared with the model group, the body weight at 16, 24, 32, 40 days into treatment in the acupoint thread-embedding group was reduced (P<0.05); the results of glucose tolerance test at 30, 60, 120 min and insulin tolerance test at 30, 60 min in the acupoint thread-embedding group were lower than those in the model group (P<0.05); the levels of total cholesterol and triacylglycerol in the acupoint thread-embedding group were significantly lower than those in the model group (P<0.01, P<0.05); the weight of epididymal adipose tissue in the acupoint thread-embedding group was significantly lower than that in the model group (P<0.01); the mRNA expression of IL-6, MCP-1, TNF-α and iNOS was reduced (P<0.05), that of IL-10, Arg-1 was increased (P<0.05), the protein expression of iNOS was down-regulated (P<0.05), and that of Arg-1 was up-regulated (P<0.01). CONCLUSION: Acupoint thread-embedding at "Zusanli" (ST 36) and "Fenglong" (ST 40) may play a role in weight control by regulating the polarization of macrophages.

Matrine attenuates pathological cardiac fibrosis via RPS5/p38 in mice.

Pathological cardiac fibrosis is a common feature in multiple cardiovascular diseases that contributes to the occurrence of heart failure and life-threatening arrhythmias. Our previous study demonstrated that matrine could attenuate doxorubicin-induced oxidative stress and cardiomyocyte apoptosis. In this study, we investigated the effect of matrine on cardiac fibrosis. Mice received aortic banding (AB) operation or continuous injection of isoprenaline (ISO) to generate pathological cardiac fibrosis and then were exposed to matrine lavage (200 mg·kg-1·d-1) or an equal volume of vehicle as the control. We found that matrine lavage significantly attenuated AB or ISO-induced fibrotic remodeling and cardiac dysfunction. We also showed that matrine (200 µmol/L) significantly inhibited the proliferation, migration, collagen production, and phenotypic transdifferentiation of cardiac fibroblasts. Mechanistically, matrine suppressed p38 activation in vivo and in vitro, and overexpression of constitutively active p38 completely abolished the protective effects of matrine. We also demonstrated that ribosomal protein S5 (RPS5) upregulation was responsible for matrine-mediated inhibition on p38 and fibrogenesis. More importantly, matrine was capable of ameliorating preexisting cardiac fibrosis in mice. In conclusion, matrine treatment attenuates cardiac fibrosis by regulating RPS5/p38 signaling in mice, and it might be a promising therapeutic agent for treating pathological cardiac fibrosis.

Prevalence and association of anxiety and depression among orthopaedic trauma inpatients: a retrospective analysis of 1994 cases.

BACKGROUND: Patients with traumatic injuries are often accompanied by emotional disorders, which seriously impede functional gains. The objective of this study was to identify the prevalence and risk factors associated with underlying anxiety and depression in orthopaedic trauma patients. METHODS: From July 2015 to December 2017, all orthopaedic trauma patients were included in the retrospective study. Patients with conditions that might affect cognitive impairment were excluded from the study. Basic demographic data were collected. All patients were screened for emotional disorders on admission using a simple questionnaire called "Huaxi Emotional-Distress Index" (HEI). Bivariate analyses and logistic regression were used to identify the factors associated with a HEI score of > 8. RESULTS: One hundred and sixty-two patients (8.1%) had a HEI score of > 8. About 1.0% of enrolled patients had severe emotional disorders (HEI score ≥ 17). The reasons caused by emotional disorders in patients with orthopaedic trauma were a higher Injury Severity Score (ISS), a higher visual analogue score (VAS) and type of surgery. On logistic regression, marital status was a protective factor for emotional disorders, while VAS and ISS were the risk factors for emotional disorders. CONCLUSIONS: Although a significantly low percentage of orthopaedic trauma patients in our setting have emotional disorders, traumatic orthopaedic surgeons still need to pay attention to the risk of emotional disorders and integrate effective screening tools into clinical practice to screen for these factors and stratify emotional disorders. Appropriate targeted psychological intervention and treatment should be adopted according to the stratification of emotional disorders.

[Effect of acupuncture on oxidative stress and apoptosis-related proteins in obese mice induced by high-fat diet].

OBJECTIVE: To explore the effect of acupuncture on oxidative stress and apoptosis-related proteins of liver in obese mice induced by high-fat diet. METHODS: A total of 45 male C57BL/6 mice were randomized into a control group (10 mice) and a model established group (35 mice). Mice in the model established group were fed with high-fat diet for 16 weeks to establish the obesity model. After model established, 30 mice were randomized into a model group, a non-acupoint group and an acupoint group, 10 mice in each one. Acupuncture was applied at "Guanyuan" (CV 4), " Zusanli" (ST 36), "Yishu" (EX-B 3) in the acupoint group and the points of 0.5 cm and 1 cm to the base of tail in the non-acupoint group, 15 min each time, once a day for 8 weeks. Mice in the control group were fed with normal diet, while mice in the other 3 groups were fed with high-fat diet continuously for 8 weeks. The body weight was measured at 0, 4th, 8th, 12th, 16th, 20th, 24th week in each group respectively. After 24-week intervention, the weight of white adipose tissue of epididymis and perirenal and liver was measured; the levels of serum alanine transaminase(ALT) and glutamic oxaloacetic aminotransferase (AST) were detected by automatic biochemical analyzer; liver homogenate was used to detect the level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD); the liver morphology was observed by HE staining; the expression of apoptosis-related proteins Bax and Bcl-2 were detected by Western blot. RESULTS: Compared with the control group, the body weight of mice in the model group, the acupoint group and the non-acupoint group was decreased on 16th week into experiment (before intervention, P<0.05); compared with the model group and the non-acupoint group, the body weight of mice in the acupoint group were decreased after intervention (P<0.05). Compared with the control group, the weight of white adipose tissue and liver, the levels of serum ALT and AST, the level of liver MDA, the expression of liver Bax were increased (P<0.05); the activity of liver SOD and the expression of liver Bcl-2 were decreased in the model group after intervention (P<0.05). Compared with the model group and the non-acupoint group, the weight of white adipose tissue and liver, the levels of serum ALT and AST, the level of liver MDA, the expression of liver Bax were decreased (P<0.05); the activity of liver SOD and the expression of liver Bcl-2 were increased in the acupoint group after intervention (P<0.05). CONCLUSION: Acupuncture at "Guanyuan" (CV 4), "Zusanli" (ST 36) and "Yishu"(EX-B 3) can improve obesity and obesity related hepatic disorder by regulating oxidative stress and inhibiting apoptosis in liver.

Osteocrin attenuates inflammation, oxidative stress, apoptosis, and cardiac dysfunction in doxorubicin-induced cardiotoxicity.

BACKGROUND: Inflammation, oxidative stress, and apoptosis contribute to the evolution of doxorubicin (DOX)-induced cardiotoxicity. Osteocrin (OSTN) is a novel secretory peptide mainly derived from the bone and skeletal muscle, and plays critical roles in regulating bone growth and physical endurance. Inspiringly, OSTN was also reported to be abundant in the myocardium that functioned as a therapeutic agent against cardiac rupture and congestive heart failure in mice after myocardial infarction. Herein, we investigated the role and potential mechanism of OSTN in DOX-induced cardiotoxicity. METHODS: Cardiac-restrict OSTN overexpression was performed by the intravenous injection of a cardiotropic AAV9 vector, and subsequently the mice received 15 mg/kg DOX injection (i.p., once) to induce acute cardiac injury. Besides, H9C2 cell lines were used to assess the possible role of OSTN in vitro by incubating with recombinant human OSTN or small interfering RNA against Ostn (siOstn). To clarify the involvement of protein kinase G (PKG), KT5823 and siPkg were used in vivo and in vitro. Mice were also administrated intraperitoneally with 5 mg/kg DOX weekly for consecutive 3 weeks at a cumulative dose of 15 mg/kg to mimic the cardiotoxic effects upon chronic DOX exposure. RESULTS: OSTN treatment notably attenuated, whereas OSTN silence exacerbated inflammation, oxidative stress, and cardiomyocyte apoptosis in DOX-treated H9C2 cells. Besides, cardiac-restrict OSTN-overexpressed mice showed an alleviated cardiac injury and malfunction upon DOX injection. Mechanistically, we found that OSTN activated PKG, while PKG inhibition abrogated the beneficial effect of OSTN in vivo and in vitro. As expected, OSTN overexpression also improved cardiac function and survival rate in mice after chronic DOX treatment. CONCLUSIONS: OSTN protects against DOX-elicited inflammation, oxidative stress, apoptosis, and cardiac dysfunction via activating PKG, and cardiac gene therapy with OSTN provides a novel therapeutic strategy against DOX-induced cardiotoxicity.