ObjectiveTo investigate the etiology and clinical features of intrahepatic cholestasis and the diagnostic value of whole exome sequencing （WES） through a retrospective analysis of the medical history， pathological results， and gene sequencing data of 62 patients with unexplained intrahepatic cholestasis. MethodsA retrospective analysis was performed for the clinical data of 480 patients who underwent WES due to unexplained liver function abnormalities in Nanjing Second Hospital from January 2017 to December 2023， among whom 62 patients with unexplained intrahepatic cholestasis were selected based on laboratory data， and a confirmed diagnosis was made based on imaging data， pathological findings， and gene sequencing data. The patients with unexplained intrahepatic cholestasis were analyzed in terms of demographic features， clinical manifestation， etiology spectrum， and genetic profile. ResultsA total of 62 patients with unexplained intrahepatic cholestasis were included， among whom there were 35 male patients and 27 female patients， with a median age of 42 （7 — ‍77） years. WES was used to make a definite diagnosis in 21 patients （33.87%）， among whom the patients with familial intrahepatic cholestasis accounted for the highest proportion of 52.38% （11/21）； genetic metabolic disorders were excluded by WES in 34 patients， with drug-induced liver injury and sepsis-associated liver injury accounting for the highest proportion of 55.88% （19/34）， followed by primary biliary cholangitis and primary sclerosing cholangitis accounting for 20.59% （7/34） and intrahepatic bile duct stones accounting for 17.65% （6/34）， while the patients with a lack of confirmed diagnosis accounted for 11.29% （7/62）. A total of 21 novel mutation sites which were not reported in previous articles were identified in this study. ConclusionGenetic metabolic disorders constitute a significant proportion of unexplained intrahepatic cholestasis， and WES plays a crucial role in the diagnosis of unexplained intrahepatic cholestasis.

ObjectiveTo explore the potential mechanism of Erchen Decoction （二陈汤， ECD） in improving metabolic syndrome （MS） with phlegm syndrome. MethodsForty mice were randomly divided into a blank group of 10 mice and a modeling group of 30 mice. The MS model with phlegm syndrome was induced in the modeling group by high-fat diet. Thirty successfully modeled mice were randomly divided into a model group， a ECD group， and a metformin group， with 10 mice in each group. The ECD group was given 0.4 g/（kg·d） of ECD， while the metformin group was intervened with 11.1 g/（kg·d） of metformin solution， and the blank group and the model group were given 0.02 ml/（g·d） of sterilized drinking water， all by gavage， once daily for 4 weeks. Body weight， abdominal circumfe-rence， body length， Lee's index and food intake were recorded. Blood glucose and blood lipid levels including fasting blood glucose， triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured. ELISA was used to detect serum leptin levels， while HE staining was used to observe liver pathological changes. Western Blot and q-PCR were used to detect protein and mRNA expression of hypothalamic leptin receptor （LepR）， pro melanocortin （POMC）， and neuropeptide Y （NPY） in the hypothalamus. Immunofluorescence was used to detect fluorescence expression of POMC and NPY in the hypothalamic arcuate nucleus region. ResultsPathological results showed that the mice in the model group had numerous fat vacuoles in hepatocytes and significant liver fat deposition， while the ECD and metformin groups showed reduced fat vacuoles and less liver fat deposition. Compared to those in the blank group， the mice in the model group mice showed liver fat deposition， increased body weight， abdominal circumference， Lee's index and food intake； fasting blood glucose， TG， TC， LDL-C， and serum leptin levels were elevated， while HDL-C was decreased； the expression of LepR， POMC protein levels and their mRNA expression decreased， while the protein level and mRNA expression of NPY increased； the fluorescence expression of POMC in the arcuate nucleus was reduced， while NPY fluorescence expression increased （P＜0.05 or P＜0.01）. Compared to the model group， the ECD group and metformin group showed significant improvements in the above indicators （P＜0.05 or P＜0.01）. Compared to the ECD group， the metformin group showed a reduction in body weight and NPY fluorescence expression， and an increase in HDL-C levels （P＜0.05 or P＜0.01）. ConclusionECD can downregulate serum leptin levels and improve glucose and lipid metabolism in the MS of phlegm syndrome. Its mechanism of action may be to reduce liver fat deposition and thereafter affect the expression of neuropeptides related to feeding activity in the hypothalamus.

Objective To analyze the monitoring status of occupational hazard factors in key industry workplaces in a city of the Pearl River Delta area from 2019 to 2023. Methods A total of 1 548 enterprises in 12 key industries of the city were selected as the research subjects using the judgmental sampling method. Their monitoring data for dust, chemical factors, and noise, along with the occupational health management status of the enterprises were analyzed. Results Among the 1 548 enterprises, large and medium-sized enterprises accounted for 2.7% and 13.4%, while small and micro enterprises accounted for 83.9%. A total of 474 enterprises exceeded the national limit in the detection of occupational hazard factors, with an exceedance rate of 30.6%. The rates of workers exposed to occupational hazard factors, dust, chemical factors, and noise were 29.4%, 6.9%, 21.0%, and 13.0%, respectively, all showing a downward trend year by year (all P<0.05). The training rates for occupational health among enterprise managers, responsible persons, and workers were 84.1%, 84.2%, and 91.2%, respectively. The detection rates for abnormal occupational health examinations among workers exposed to dust, chemical factors, and noise were 0.2%, 0.3%, and 0.5%, respectively. The setting rates of warning signs and warning instructions among enterprises for dust, chemical toxins, and noise were 87.3%, 91.1%, and 89.5%, respectively. The setting rates for dust, toxic chemical, and noise control facilities were 72.4%, 75.4%, and 46.0%, with effectiveness rates of 70.5%, 56.6%, and 55.2%, respectively. The distribution rates of personal protective dust masks, gas masks, and noise earplugs/earmuffs were 91.9%, 83.8%, and 86.4%, with wearing rates of 80.8%, 70.5%, and 76.4%, respectively. The detection rates of exceeding national limits for dust, chemical factors, and noise in the work site of occupational hazard factors were15.2%, 1.0%, and 21.6%, respectively. The detection rates of exceeding national limits for dust, chemical factors, and noise in the workplace of occupational hazard factors were 2.4%, 2.5%, and 12.3%, respectively. The exceedance rate for noise in work site showed an upward trend year by year (P<0.01). Conclusion Occupational disease prevention and control work in the key industries of this city needs strengthening. It is essential to further enhance the regular monitoring and preventive measures of occupational hazard factors in enterprises, improve protective measures, strengthen the use of personal protective equipment, and enhance occupational health training and supervision, to effectively reduce the risk of occupational diseases and protect workers' occupational health rights.

BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

By reviewing modern research and integrating clinical practice， this paper elucidates the correlation between the traditional Chinese medicine theory of pathological accumulation from collateral obstruction and gap junction intercellular communication （GJIC）， as well as its theoretical connotation and clinical application in tumor prevention and treatment. Physiologically， gap junction and collateral channels share similarities in structural distribution， substance exchange and information transmission. Pathologically， metabolic coupling mediated by dysfunctional gap junction resembles collaterals stagnation， forming the basis of tumor pathogenesis. The establishment of heterotypic gap junction parallels collateral hyperactivity， contributing to tumor metastasis. The post-translational modifications （PTMs） disorder of connexins is similar to the deficiency of collaterals， serving as a driver of tumor progression. Clinically， tumor treatment should follow the pathomechanism of collateral obstruction leading to pathological accumulation. In the early stage， detoxifying and unblocking collaterals can restore intercellular communication and inhibit tumorigenesis； in the progressive stage， calming hyperactivity and suppressing aberrant collateral pathways can prevent metastasis by interrupting heterotypic gap junction formation； and in the terminal stage， supporting vital qi and modulating PTMs of connexins can help delay tumor progression.

BackgroundFear of progression is one of the typical psychological consequences in patients with chronic obstructive pulmonary disease （COPD）. The level of fear of progression is affected by the illness perception status， and the link between social support and fear of progression is acknowledged， whereas the mechanism underlying the three remains unclear due to the lack of empirical research evidence and needs to be further studied. ObjectiveTo explore the mediating role of social support in the relationship between illness perception and fear of progression in COPD patients， and to provide references for effectively alleviating fear in COPD patients. MethodsA total of 435 COPD patients admitted to the Department of Respiratory and Critical Care Medicine， the Affiliated Hospital of Southwest Medical University from March 9 to July 31， 2024 were selected as the study objects. The Chinese version of Fear of Progression Questionnaire-Short Form （FoP-Q-SF）， Chinese version of Brief Illness Perception Questionnaire （BIPQ） and Social Support Rate Scale （SSRS） were used for the evaluation. Pearson's coefficient was calculated to assess the correlation among above scales. Model 4 of the Process macro 3.4.1 for SPSS 25.0 was used to test the mediating effect of social support on the relationship between illness perception and fear of progression， with Bootstrapping used to evaluate the significance of mediating effect. ResultsA total of 412 patients （94.71%） completed this study.BIPQ score was positively correlated with FoP-Q-SF score （r=0.238， P<0.01）， and negatively correlated with SSRS score in COPD patients （r=-0.260， P<0.01）. FoP-Q-SF score was negatively correlated with SSRS score （r=-0.271， P<0.01）. Social support mediated the relationship between illness perception and fear of progression， with an indirect effect value of 0.025 （95% CI： 0.009~0.041）， accounting for 13.02% of the total effect. ConclusionIllness perception can affect the fear of progression in COPD patients both directly and indirectly through social support. ［Funded by Nursing Research Project of Sichuan Province （number， H22010）］

ObjectiveTo multidimensionally analyze the clinical effects of Qianyang Yuyin granules on elderly hypertensive patients through an "energy-inflammation-aging" network. MethodsRelevant datasets were retrieved from the GEO database. Gene set enrichment analysis （GSEA） was performed on the gene expression profiles of peripheral blood cells from patients with essential hypertension in dataset GSE24752. The GSEA referenced "GO gene sets" and "KEGG gene sets" to identify significantly enriched gene sets. A clinical trial was conducted using a randomized controlled study design. A total of 40 patients meeting the inclusion criteria were enrolled. The control group received standard antihypertensive treatment with angiotensin receptor blockers （ARBs） or combined calcium channel blockers （CCBs）. In contrast，the treatment group received Qianyang Yuyin Granules in addition to the standard treatment for 12 weeks. Blood pressure levels and clinical efficacy were observed，and changes in energy metabolism indicators，DNA damage markers，and senescence-associated secretory phenotype （SASP） in blood were measured using ELISA before and after treatment. ResultsGSEA results indicated significant energy metabolism dysregulation in hypertensive patients. Clinical findings showed that both groups achieved blood pressure control without significant intergroup differences. In terms of clinical efficacy，the treatment group had a significantly higher effective rate compared to the control group （95% vs 65%，P0.05）. After treatment，the treatment group showed a significant increase in NAD⁺ levels （P0.01），with higher levels compared to the control group （P0.05）. The treatment group also exhibited a greater reduction in DNA damage marker 8-OHdG （P0.01） and cell adhesion factors ICAM-1 and VCAM-1 （P0.01） compared to the control group. Pro-inflammatory cytokines IL-1β and IL-6 were significantly reduced in the treatment group （P0.01），with greater reductions compared to the control group （P0.05，P0.01）. Anti-inflammatory cytokines IFN-α，IL-4，and IL-10 were significantly elevated in the treatment group （P0.01），with higher levels compared to the control group （P0.01）. No significant adverse reactions were reported in either group. ConclusionThe "energy- inflammation- aging" network plays an important role in the pathological mechanism of hypertension patients. Qianyang Yuyin granules may delay the aging process by increasing patients' energy metabolism levels，reducing DNA oxidative damage，and maintaining the balance of inflammatory factors.

Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology* ; Humans ; Animals ; Calcium/metabolism* ; Calcium Signaling/physiology* ; Brain/physiology* ; Aging/physiology* ; Membrane Microdomains/physiology* ; Neurodegenerative Diseases/physiopathology*

In China, the number of chronic pain patients has exceeded 300 million, making chronic pain the third major health problem after tumors and cardiovascular diseases. Particularly concerning is the gradual emergence of hypertension and chronic low back pain as public health problems that threaten public health and increase the global economic burden. Modern research shows that the incidence of coexisting hypertension is higher among patients with chronic low back pain. Additionally, evidence indicates that the use of NSAIDs for pain relief can have adverse effects on blood pressure, and some antihypertensive medications may trigger symptoms of low back pain. Thus, addressing chronic pain in hypertensive patients while stabilizing blood pressure is one of the important research questions in the modern treatment of hypertension among middle-aged and elderly individuals. From ancient to modern traditional Chinese medicine(TCM) theory, kidney deficiency has been regarded as the core pathogenesis of low back pain. Recent clinical practices and literature indicate that kidney deficiency plays a crucial role in the modern pathogenesis of hypertension. Both hypertension and chronic low back pain are closely associated with kidney deficiency in TCM theory, revealing a potential mechanism linking the two conditions. Combining the theories of " kidney-essence-marrow" and " nourishing water to moisten wood", a therapeutic strategy centered on tobifying kidney was proposed, including selecting single drugs with kidney-tonifying effects as well as compound formulations and elaborating modern research evidence. The aim is to achieve stable blood pressure control in hypertension patients with chronic low back pain while providing a new treatment perspective for chronic low back pain. This article systematically elaborates on the understanding of hypertension combined with chronic low back pain from both TCM and modern medicine, as well as the therapeutic strategy involving kidney-tonifying drugs, to offer useful references for clinical practice.
Humans ; Hypertension/complications* ; Low Back Pain/complications* ; Drugs, Chinese Herbal/therapeutic use* ; Kidney/drug effects* ; Medicine, Chinese Traditional ; Chronic Pain/drug therapy*