Aspects of public health development in China's western region.

The public health level in a country is closely related to national development and quality of life. In order to appraise the level of health services in the western region of China, panel data of 124 prefecture-level units covering the period 2011 to 2021 was used together with a health evaluation index system based on four dimensions: quality of life, environmental situation, the level of health services and longevity. To assess this, we used entropy weights, standard deviation and coefficient of variation together with the geographical detector model that measures the stratified spatial heterogeneity. The results show that although public health services have improved overall, the various dimensions are still not balanced as longevity did not match up everywhere. While the developmental level of the various health dimensions presents a pattern of a relatively smooth increasing gradient in the west-central- east direction, the situation with respect to the north-centralsouth is more uneven with both ups and downs. However, a trend of continuous enhancement of all health dimensions was found with a significant positive correlation of spatial clustering, with hotspots and 'sub-hotspots' contracting from north to south, while coldspots and 'sub-coldspots' expanded from west to east. This can be seen as the result of multiple factors, with the level of urbanization and economic level as the dominant factors and government guidance, agglomeration capacity and industrial structure being auxiliary.

Myeloid Vamp3 deletion attenuates CFA-induced inflammation and pain in mice via ameliorating macrophage infiltration and inflammatory cytokine production.

Persistent inflammation and associated pain significantly impact individuals' quality of life, posing substantial healthcare challenges. Proinflammatory cytokines, released by activated macrophages, play crucial roles in the development of chronic inflammatory conditions such as rheumatoid arthritis. To identify and evaluate potential therapeutic interventions targeting this process for mitigating inflammation and pain, we created myeloid cell-specific knockout of Vamp3 (vesicle-associated membrane protein 3) mice (Vamp3 Δmyel) by crossing LysM-Cre mice with newly engineered Vamp3flox/flox mice. Bone marrow-derived macrophages and peritoneal resident macrophages from Vamp3 Δmyel mice exhibited a significant reduction in TNF-α and IL-6 release compared to control mice. Moreover, Vamp3 deficiency led to decreased paw edema and ankle joint swelling induced by intraplantar injection of complete Freund's adjuvant (CFA). Furthermore, Vamp3 depletion also mitigated CFA-induced mechanical allodynia and thermal hyperalgesia. Mechanistically, Vamp3 loss ameliorated the infiltration of macrophages in peripheral sites of the hind paw and resulted in reduced levels of TNF-α and IL-6 in the CFA-injected paw and serum. RT-qPCR analysis demonstrated downregulation of various inflammation-associated genes, including TNF-α, IL-6, IL-1ß, CXCL11, TIMP-1, COX-2, CD68, and CD54 in the injected paw at the test day 14 following CFA administration. These findings highlight the novel role of Vamp3 in regulating inflammatory responses and suggest it as a potential therapeutic target for the development of novel Vamp-inactivating therapeutics, with potential applications in the management of inflammatory diseases.

Nonlinear relationship between dietary calcium and magnesium intake and peripheral neuropathy in the general population of the United States.

Background: Calcium and magnesium are essential minerals that have significant roles in nerve function and regulation. There may be a correlation between dietary calcium and magnesium intake and peripheral neuropathy. However, this relationship remains unclear and requires further study. Methods: Data from 7,726 participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004 were analyzed in this study. The relationship between total dietary calcium and magnesium intake, as well as each quantile, and peripheral neuropathy was analyzed using a multifactor logistic regression model. To illustrate the dose-response relationship between calcium and magnesium intake and peripheral neuropathy, we utilized a restricted cubic spline (RCS) plot. Results: Our analysis found a positive correlation between dietary intake of calcium and magnesium and peripheral neuropathy (calcium: OR 1.000, 95% CI 1.000-1.000; magnesium: OR 1.001, 95% CI 1.00-1.002). Participants in the first and third quantiles of dietary calcium intake had a significantly higher incidence of peripheral neuropathy than those in the second quantile (OR 1.333, 95% CI 1.034-1.719, OR 1.497, 95% CI 1.155-1.941). Those in the first and third quantiles of dietary magnesium intake also had a significantly higher incidence of peripheral neuropathy than those in the second quantile (OR 1.275, 95% CI 1.064-1.528, OR 1.525, 95% CI 1.231-1.890). The restricted cubic spline analysis revealed a U-shaped nonlinear relationship between dietary intake of calcium and magnesium and peripheral neuropathy. Conclusion: The study found a U-shaped non-linear relationship between dietary calcium and magnesium intake levels and peripheral neuropathy, indicating that both excessive and insufficient intake of calcium and magnesium can increase the incidence of peripheral neuropathy.

Trends and bibliometric analysis on pediatric anesthesia from 2002 to 2022: A review.

Pediatric anesthesia is one of the most concerning topics in our society. However, there is still a lack of a comprehensive overview of the research base and of future trends. This study aimed to guide beginners quickly learn the academic research on pediatric anesthesia and do their own studies by analyzing the articles of this field in the latest 21 years through bibliometric analysis. Literature scanning was conducted with the Web of Science database. Microsoft Excel, SPSS, VOSviewer, and CiteSpace were in this review. There was an increasing trend of articles on pediatric anesthesia, based on the analysis of 11,591 included articles. The top 3 most productive countries were the United States of America (4538), Canada (730) and Turkey (688). The most productive institutions were Boston Childrens hospital, Childrens Hospital Philadelphia and Ohio State University. Tobias, Joseph D (141), Kim, Hee-Soo (40) and Curley, Martha A Q (38) were the most active authors. Habre W (2017), Gross JB (2002) and Cravero JP (2009) are the articles cited more than 100 times during the analysis years. Anesthesia and Analgesia, Anesthesiology, Pediatric Anesthesia, were the core journals in this field. Cohort, simulation, sleep, postoperative complication are strongest burst keywords in recent years. This article summarizes the authoritative institutions, authors, literatures and frontier hotspots on pediatric anesthesia. Itwill be a valuable literature review and help beginners to quickly get started in the field, reduce unnecessary clueless and aimless learning, and greatly improve learning efficiency.

DNA methylation of HOX genes and its clinical implications in cancer.

Homeobox (HOX) genes encode highly conserved transcription factors that play vital roles in embryonic development. DNA methylation is a pivotal regulatory epigenetic signaling mark responsible for regulating gene expression. Abnormal DNA methylation is largely associated with the aberrant expression of HOX genes, which is implicated in a broad range of human diseases, including cancer. Numerous studies have clarified the mechanisms of DNA methylation in both physiological and pathological processes. In this review, we focus on how DNA methylation regulates HOX genes and briefly discuss drug development approaches targeting these mechanisms.

Cardiopulmonary bypass in a rat model may shorten the lifespan of stored red blood cells by activating caspase-3.

BACKGROUND: Red blood cell transfusion is required for many types of surgery against cardiovascular disease, and the function of transfused cells appears to decline over time. The present study examined whether transfusion also reduces red blood cell lifespan in a rat model. MATERIAL AND METHODS: Bypass in rats were established by connecting a roll pump to the femoral artery and vein. Then FITC-labeled stored red blood cells from rats were transfused in the animals, and the cells in circulation were counted after transfusion. In separate experiments, stored red blood cells were incubated with bypass plasma in vitro, and the effects of incubation were assessed on cell morphology, redox activity, ATP level, caspase-3 activity, and phosphatidylserine exposure on the cell surface. These in vivo and in vitro experiments were also performed after pretreating the stored red blood cells with the caspase-3 inhibitor Z-DEVD-FMK. RESULTS: Bypass significantly decreased the number of circulating FITC-labeled stored red blood cells and increased the proportions of monocytes, neutrophils and splenic macrophages that had phagocytosed the red blood cells. In vitro, bypass plasma altered the morphology of red blood cells and increased oxidative stress, caspase-3 activity and phosphatidylserine exposure, while decreasing ATP level. Pretreating stored red blood cells with Z-DEVD-FMK attenuated the effects of bypass on caspase-3 activity, but not oxidative stress, in stored red blood cells. DISCUSSION: Bypass appears to shorten the lifespan of stored red blood cells, at least in part by activating caspase-3 in the cells.

Effects of CAR-T Cell Therapy on Immune Cells and Related Toxic Side Effect Analysis in Patients with Refractory Acute Lymphoblastic Leukemia.

Objective: To observe the effects of chimeric antigen receptor T (CAR-T) cell immunotherapy on immune cells and related toxic side effects in patients with refractory acute lymphoblastic leukemia (ALL). Methods: A retrospective study was conducted in 35 patients with refractory ALL. The patients were treated with CAR-T cell therapy in our hospital from January 2020 to January 2021. The efficacy was evaluated at one and three months post treatments. The venous blood of the patients was collected before treatment, 1 month after treatment, and 3 months after treatment. The percentage of regulatory T cells (Treg cells), natural killer (NK) cells, and T lymphocyte subsets (CD3+, CD4+, and CD8+ T cells) was detected by flow cytometry. The ratio of CD4+/CD8+ was calculated. Patient's toxic side effects such as fever, chills, gastrointestinal bleeding, nervous system symptoms, digestive system symptoms, abnormal liver function, and blood coagulation dysfunction were monitored and recorded. The incidence of toxic and side effects was calculated, and the incidence of infection was recorded. Results: After one month of CAR-T cell therapy in 35 patients with ALL, the efficacy evaluation showed that complete response (CR) patients accounted for 68.57%, CR with incomplete hematological recovery (CRi) patients accounted for 22.86%, and partial disease (PD) patients accounted for 8.57%, and the total effective rate was 91.43%. In addition, compared with that before treatment, the Treg cell level in CR+CRi patients treated for 1 month and 3 months decreased prominently, and the NK cell level increased dramatically (P < 0.05). Compared with that before treatment, the levels of CD3+, CD4+, and CD4+/CD8+ in patients with CR+CRi in the 1-month and 3-month groups were markedly higher, and the levels of CD4+/CD8+ in the 3-month group were memorably higher than those in the 1-month group (P < 0.05). During CAR-T cell therapy in 35 patients with ALL, fever accounted for 62.86%, chills for 20.00%, gastrointestinal bleeding for 8.57%, nervous system symptoms for 14.29%, digestive system symptoms for 28.57%, abnormal liver function for 11.43%, and coagulation dysfunction for 8.57%. These side effects were all relieved after symptomatic treatment. During the course of CAR-T therapy in 35 patients with ALL, 2 patients had biliary tract infection and 13 patients had lung infection. No correlations were found between the infection and age, gender, CRS grade, usage of glucocorticoids or tocilizumab, and laboratory indicators such as WBC, ANC, PLT, and Hb (P > 0.05). Conclusion: CAR-T cell therapy had a good effect on patients with refractory ALL by regulating the immune function of the body via mediating the content of immune cells. CAR-T cell therapy may have therapeutic effect on refractory ALL patients with mild side effects and high safety.

The association between serum albumin levels and related metabolic factors and atrial fibrillation: A retrospective study.

The association between serum albumin (ALB) and cardiovascular events has been well established, but the relationship with atrial fibrillation (AF) remains controversial. This study aims to evaluate the association between ALB and AF in a Chinese population. We reviewed the medical records of 2000 hospitalized patients, 1000 patients with AF were included in the AF group, and 1000 age- and sex-matched patients with sinus rhythm and no history of AF were included in the control group. The T test or chi-square test were conducted to analyze clinical baseline data. Logistic regression analysis was conducted to assess the relationship between AF and ALB. The interrelationships of ALB were analyzed by Pearson correlation analyses. The appropriate cutoff value of ALB for AF was analyzed by receiver operating characteristic curves. ALB levels were lower in the AF group than in the control group (P < .05). After multivariable adjustment, ALB was independently negatively associated with AF (odds ratio = 0.935, 95% confidence interval: 0.905-0.965, P < .05). ALB levels were positively correlated with serum globulin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, serum apolipoprotein A1, and serum apolipoprotein B levels (P < .05), but negatively correlated with serum creatinine levels (P < .05). The optimal cutoff value of ALB for predicting AF was 37.25 g/L, the sensitivity was 78.0%, and the specificity was 4.6%. Low ALB level is independently associated with AF. Since the current study design cannot establish causalities, further prospective cohort studies are needed to determine this finding.

IL-20 promotes cutaneous inflammation and peripheral itch sensation in atopic dermatitis.

Atopic dermatitis (AD) is a chronic skin disease, which is associated with intense itch, skin barrier dysfunction and eczematous lesions. Aberrant IL-20 expression has been implicated in numerous inflammatory diseases, including psoriasis. However, the role of IL-20 in AD remains unknown. Here, RNA-seq, Q-PCR, and immunocytochemistry were utilized to examine disease-driven changes of IL-20 and its cognate receptor subunits in skin from healthy human subjects, AD patients and murine AD-models. Calcium imaging, knockdown and cytokine array were used to investigate IL-20-evoked responses in keratinocytes and sensory neurons. The murine cheek model and behavioral scoring were employed to evaluate IL-20-elicited sensations in vivo. We found that transcripts and protein of IL-20 were upregulated in skin from human AD and murine AD-like models. Topical MC903 treatment in mice ear enhanced IL-20R1 expression in the trigeminal sensory ganglia, suggesting a lesion-associated and epidermal-driven mechanism for sensitization of sensory IL-20 signaling. IL-20 triggered calcium influx in both keratinocytes and sensory neurons, and promoted their AD-related molecule release and transcription of itch-related genes. In sensory neurons, IL-20 application increased TLR2 transcripts, implicating a link between innate immune response and IL-20. In a murine cheek model of acute itch, intradermal injection IL-20 and IL-13 elicited significant itch-like behavior, though only when co-injected. Our findings provide novel insights into IL-20 function in peripheral (skin-derived) itch and clinically relevant intercellular neuron-epidermal communication, highlighting a role of IL-20 signaling in the pathophysiology of AD, thus forming a new basis for the development of a novel antipruritic strategy via interrupting IL-20 epidermal pathways.

Flip-over of blood vessel intima caused by vascular closure device: A case report.

BACKGROUND: Complications of vascular closure devices mainly include bleeding, vascular injury, and trapped device that cannot be removed percutaneously. However, arterial stenosis or occlusion induced by vascular injury is rare. This article introduces a rare case with severe acute limb ischemia after using the vascular closure device (StarClose). CASE SUMMARY: A 54-year-old man was admitted because of necrosis of the second toe of the left foot for 2 mo. Ultrasound showed left femoral artery stenosis, and occlusion of the left popliteal, posterior tibial, peroneal, anterior tibial and dorsalis pedis arteries, suggesting arteriosclerosis obliterans of low extremities, gangrene and type 2 diabetes. He underwent an interventional procedure of drug-eluting balloon in the left lower limb via antegrade puncture of the left common femoral artery. He developed acute limb ischemia after 1 h, and severe pain, numbness, pale skin, low skin temperature and weakened sensation in the left foot. Injury of the common femoral artery intima was considered. Exploratory surgery showed occlusion at the puncture point accompanied with bulged vascular lumen and flipped vascular intima caused by StarClose. The flipped intima was removed. The limb blood supply was restored and the limb was saved post-surgery. He recovered well at final follow-up. CONCLUSION: Incorrect use of the vascular closure device was the main cause of severe acute limb ischemia in this case.

Analysis of the efficacy and safety of Danshen Dripping pills on the eyes of diabetic retinopathy patients with Qi stagnation and blood stasis.

OBJECTIVE: To analyze the efficacy and safety of compound Danshen dripping pills (CDDPs) in the treatment of patients with diabetic retinopathy (DR) with the syndrome of Qi stagnation and blood stasis. METHODS: The clinical data of 81 patients with DR admitted to our hospital were analyzed retrospectively, and the patients were divided into an observation group (n=40) and a control group (n=41) in accordance with a random number table. The observation group was treated with CDDPs, while the control group was treated with Captopril. The response rates, change of severity degrees of retinopathy, improvement of vision, incidence of macular edema and symptom scores were compared between the two groups. RESULTS: (1) The ratio of decreasing degree of severity of retinopathy in the observation group was greater than that in the control group, while the ratio of increasing degree of severity of retinopathy in the observation group was lower than that in the control group (P < 0.05). There was no significant difference in the constant ratio of degree of severity of retinopathy between the two groups (P > 0.05). (2) After treatment, the scores for dim vision, somber facial complexion, dry eyes, encrusted skin and numbness of the limbs in the observation group were lower than those in the control group (P < 0.05). (3) The overall response rates (ORRs) were 87.50% and 63.41% in the observation group and the control group, respectively (P < 0.05). (4) After treatment, the vision in the left and right eye in the observation group was higher than those in the control group (P < 0.05). (5) The incidence rates of macular edema were 12.50% and 31.71% in the observation group and the control group, respectively (P < 0.05). CONCLUSION: CDDPs can effectively elevate the response rate, reduce the degree of severity of retinopathy, mitigate the incidence of macular edema, and improve the vision of DR patients with the syndrome of Qi stagnation and blood stasis, exhibiting a satisfactory safety profile. Therefore, it has a good application value.

Epigallocatechin-3-gallate prevents inflammation and diabetes -Induced glucose tolerance through inhibition of NLRP3 inflammasome activation.

Epigallocatechin-3-gallate (EGCG), the primary polyphenol component of green tea, has been shown to inhibit both oxidation and inflammation. However, the exact mechanism through which EGCG exhibits anti-inflammatory effects remains unclear. In this study, we assessed the potential pathways by which EGCG regulates NLRP3 inflammasome activity in vitro. We found that EGCG inhibits caspase-1 activation and IL-1ß secretion by suppressing NLRP3 inflammasome activation in mouse bone marrow-derived macrophages (BMDMs). EGCG was also observed to block NLRP3-mediated ASC speckle formation and to alleviate pyroptosis in BMDMs. In addition, EGCG treatment could improve high-fat diet (HFD)-induced glucose tolerance and prevent NLRP3 inflammasome-dependent inflammation in a mouse model of HFD-induced type 2 diabetes (T2D). Taken together, our results show that EGCG is a general inhibitor of NLRP3 inflammasome activation and administration of EGCG in T2D mice could improve glucose tolerance in vivo.

A novel tumor suppressor ZBTB1 regulates tamoxifen resistance and aerobic glycolysis through suppressing HER2 expression in breast cancer.

Transcriptional repressor zinc finger and BTB domain containing 1 (ZBTB1) is required for DNA repair. Because DNA repair defects often underlie genome instability and tumorigenesis, we determined to study the role of ZBTB1 in cancer. In this study, we found that ZBTB1 is down-regulated in breast cancer and this down-regulation is associated with poor outcome of breast cancer patients. ZBTB1 suppresses breast cancer cell proliferation and tumor growth. The majority of breast cancers are estrogen receptor (ER) positive and selective estrogen receptor modulators such as tamoxifen have been widely used in the treatment of these patients. Unfortunately, many patients develop resistance to endocrine therapy. Tamoxifen-resistant cancer cells often exhibit higher HER2 expression and an increase of glycolysis. Our data revealed that ZBTB1 plays a critical role in tamoxifen resistance in vitro and in vivo To see if ZBTB1 regulates HER2 expression, we tested the recruitments of ZBTB1 on HER2 regulatory sequences. We observed that over-expressed ZBTB1 occupies the estrogen receptor α (ERα)-binding site of the HER2 intron in tamoxifen-resistant cells, suppressing tamoxifen-induced transcription. In an effort to identify potential microRNAs (miRNAs) regulating ZBTB1, we found that miR-23b-3p directly targets ZBTB1. MiR-23b-3p regulates HER2 expression and tamoxifen resistance via targeting ZBTB1. Finally, we found that miR-23b-3p/ZBTB1 regulates aerobic glycolysis in tamoxifen-resistant cells. Together, our data demonstrate that ZBTB1 is a tumor suppressor in breast cancer cells and that targeting the miR-23b-3p/ZBTB1 may serve as a potential therapeutic approach for the treatment of tamoxifen resistant breast cancer.

A Liposomal Formulation for Improving Solubility and Oral Bioavailability of Nifedipine.

Proliposomes were used to improve the solubility and oral bioavailability of nifedipine. Nifedipine proliposomes were prepared by methanol injection-spray drying method. The response surface method was used to optimize formulation to enhance the encapsulation efficiency (EE%) of nifedipine. The particle size of nifedipine proliposomes after rehydration was 114 nm. Surface morphology of nifedipine proliposomes was observed by a scanning electron microscope (SEM) and interaction of formulation ingredients was assessed by differential scanning calorimetry (DSC). The solubility of nifedipine is improved 24.8 times after forming proliposomes. In vitro release experiment, nifedipine proliposomes had a control release effect, especially in simulated gastric fluid. In vivo, nifedipine proliposomes significantly improved the bioavailability of nifedipine. The area under the concentration-time curve (AUC0-∞) of nifedipine proliposomes was about 10 times than nifedipine after oral administration. The elimination half-life (T1/2ß) of nifedipine was increased from 1.6 h to 6.6 h. In conclusion, proliposomes was a promising system to deliver nifedipine through oral route and warranted further investigation.

BDNF and NGF signals originating from sensory ganglia promote cranial motor axon growth.

After exiting the hindbrain, branchial motor axons reach their targets in association with sensory ganglia. The trigeminal ganglion has been shown to promote motor axon growth from rhombomeres 2/3 and 4/5, but it is unknown whether this effect is ganglion specific and through which signals it is mediated. Here, we addressed these questions by co-cultures of ventral rhombomere 8 explants with cranial and spinal sensory ganglia in a collagen gel matrix. Our results show that all cranial sensory ganglia and even a trunk dorsal root ganglion can promote motor axon growth and that ganglia isolated from older embryos had a stronger effect on the axonal growth than younger ones. We found that brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are necessary and sufficient for this effect. Altogether, our results demonstrate that the promoting effect of sensory ganglia on cranial motor axon growth is stage dependent, but not ganglion specific and is mediated by BDNF and NGF signals.

Liposomal Vitamin D3 as an Anti-aging Agent for the Skin.

Vitamin D3 is an effective skin protective substance to prevent photoaging. Liposomes were used as a carrier to deliver vitamin D3 to improve the stability and to enhance the treatment effect of vitamin D3. The stability of vitamin D3 liposomes, average cumulative penetration, and retention of vitamin D3 in the skin were then evaluated and compared with free vitamin D3. Finally, the treatment effect of vitamin D3 liposomes in a rat photoaging model was appraised and Haematoxylin-Eosin (H&E) staining was used to assess the histology changes of the skin after vitamin D3 liposome treatment. The results indicated that liposomes could significantly improve the stability of vitamin D3. The average skin retention of vitamin D3 liposomes was 1.65 times that of the vitamin D3 solution. Vitamin D3 liposomes could repair the surface morphology of skin in the photoaging model and promote the production of new collagen fibers. Vitamin D3 liposomes as a potential skin care agent could significantly improve skin appearance and repair damage in the histology of photoaging.

Norcantharidin regulates ERα signaling and tamoxifen resistance via targeting miR-873/CDK3 in breast cancer cells.

MiR-873/CDK3 has been shown to play a critical role in ERα signaling and tamoxifen resistance. Thus, targeting this pathway may be a potential therapeutic approach for the treatment of ER positive breast cancer especially tamoxifen resistant subtype. Here we report that Norcantharidin (NCTD), currently used clinically as an ani-cancer drug in China, regulates miR-873/CDK3 axis in breast cancer cells. NCTD decreases the transcriptional activity of ERα but not ERß through the modulation of miR-873/CDK3 axis. We also found that NCTD inhibits cell proliferation and tumor growth and miR-873/CDK3 axis mediates cell proliferation suppression of NCTD. More important, we found that NCTD sensitizes resistant cells to tamoxifen. NCTD inhibits tamoxifen induced the transcriptional activity as well ERα downstream gene expressions in tamoxifen resistant breast cancer cells. In addition, we found that NCTD restores tamoxifen induced recruitments of ERα co-repressors N-CoR and SMRT. Knockdown of miR-873 and overexpression of CDK3 diminish the effect of NCTD on tamoxifen resistance. Our data shows that NCTD regulates ERα signaling and tamoxifen resistance by targeting miR-873/CDK3 axis in breast cancer cells. This study may provide an alternative therapy strategy for tamoxifen resistant breast cancer.