Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.

Objective: To investigate the therapeutic effect of patchouli alcohol on mice with lung-heat syndrome based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/nuclear factor-kappa B(NF-κB) signaling pathway. Methods: First, network pharmacology was used to predict the potential targets of patchouli alcohol in the treatment of lung-heat syndrome, and a "component-disease-key target" network was constructed for pathway analysis. Then, 40 BALB/c mice were assigned to the normal, lung-heat model, honeysuckle, and low-dose and high-dose patchouli alcohol groups. All groups, except the blank group, were intranasally infected with 50 μL (103 TCID50) of influenza virus solution. After two hours of infection, mice were treated once a day for seven consecutive days. The therapeutic mechanism of patchouli alcohol was explored by measuring pulmonary inflammatory factors, the PI3K/Akt/NF-κB pathway, hypothalamic fever markers (PGE2, cAMP, cGMP levels), rectal temperature, and tissue energy metabolism. Results: Network pharmacology identified 135 target genes related to patchouli alcohol and lung-heat syndrome, with the key targets being STAT3, H1F1A, and NF-κB1. In animal experiments, patchouli alcohol significantly alleviated influenza virus-induced lung inflammatory damage in mice with lung-heat syndrome, inhibited the expression of TNF-α and IL-6 in lung tissues(P<0.01), and suppressed the activation of the PI3K/Akt/NF-κB pathway. It also reduced hypothalamic levels of PGE2 and cAMP(P<0.01), suppressed the increase in rectal temperature, significantly decreased liver glycogen and pyruvate levels(P<0.01), and increased the activities of SDH, LDH, and Na+ -K+ -ATPase in the liver(P<0.01) Conclusion Patchouli alcohol improves the symptoms of lung-heat syndrome in mice by inhibiting the activation of the PI3K/Akt/NF-κB pathway, reducing proinflammatory cytokines and inflammatory damage, and regulating hypothalamic fever markers and energy metabolism.

Objective: To investigate the biological effects of carvacrol on rats with stomach-heat and stomach-cold and its regulation on transient receptor potential(TRP) channels in rats with stomach-heat, and to study the cold and heat properties of carvacrol and its possible mechanism. Methods: According to the random number method, 100 SD rats were divided into stomach-heat blank group, stomach-heat model group, Coptidis Rhizoma group, stomach-heat low-dose and high-dose carvacrol group, stomach-cold blank group, stomach-cold model group, Baked ginger group, stomach-cold low-dose group and high-dose carvacrol group, 10 rats in each group. The rat model of stomach-heat was established by intragastric administration of pepper aqueous solution (0.80 g/kg) and anhydrous ethanol, and the rat model of stomach-cold was established by intragastric administration of water extract of Anemarrhena asphodeloides and sodium hydroxide (10.40 g/kg). On the day of modeling, the rats in the Baked ginger group were given Baked ginger decoction (0.78 g/kg), and the rats in the Coptidis Rhizoma group were given Coptidis Rhizoma decoction (0.43 g/kg).The stomach-cold and stomach-heat low-dose group of carvacrol was given carvacrol emulsion (40 mg/kg), high-dose group was given carvacrol emulsion (80 mg/kg).All rats of the blank and model groups were given the equal volume of emulsion prepared by 5% dimethyl sulfoxide, 1% Tween 80, 1% polyethylene glycol 400, and 93% normal saline, once a day, for 7 days. The general condition of rats was observed and the body mass was recorded. The pathological morphology of gastric tissue was observed by hematoxylin-eosin staining. The changes of material and energy metabolism, cyclic nucleotide (cAMP), thyroid hormone and gastrointestinal hormone in each group were determined by enzyme-linked immunosorbent assay. The expression levels of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential channel M8 (TRPM8) and uncoupling protein-1 (UCP1) in rats with gastric fever were detected by Western blotting. Results: Compared with the stomach-heat blank group, the body mass of rats in the stomach-heat model group decreased at the fifth and seventh day (P<0.05). The contents (or ratio) of hepatic glycogen (HGlyc), total cholesterol (TC), triglyceride (TG), and vasoactive intestinal peptide (VIP) were decreased (P<0.05), and Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cytochrome C oxidase (COX), NADH dehydrogenase (ND), cyclic adenosine phosphate (cAMP), cAMP/cyclic guanosine phosphate (cGMP), triiodothyronine (T3), thyroxine (T4), gastrin (GAS), motilin (MTL), and α-amylase (α-AMS) all increased (P<0.05). Compared with the stomach-heat model group, the body mass of rats in the Coptidis Rhizoma group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, VIP and α-AMS were increased, and Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and GAS all decreased (P<0.05). The body mass of rats in the stomach-heat low-dose carvacrol group decreased at the seventh day. The contents (or ratio) of HGlyc, TC, and VIP were increased, Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and MTL all decreased, the expression of TRPV1 and UCP1 in gastric tissue decreased, while TRPM8 increased (P<0.05) in rats of the stomach-heat low-dose and high-dose carvacrol groups. Compared with the stomach-cold blank group, the body mass of rats in the stomach-cold model group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, α-AMS, and VIP all increased, while Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, GAS, and MTL all decreased (P<0.05). Compared with the stomach-cold model group, the body mass of rats in the Baked ginger group was increased at the seventh day, and the contents (or ratio) of HGlyc, VIP, and α-AMS all decreased, while Na+ -K+ -ATPase, COX, ND, cAMP/cGMP, T3, T4, GAS, and MTL all increased (P<0.05). The contents of HGlyc, cAMP, α-AMS, and VIP of rats in the stomach-cold low and high-dose carvacrol group all decreased (P<0.05). TG in the stomach-cold low-dose carvacrol group was increased. TC, Ca2+ -Mg2+ -ATPase, and cGMP all increased, while cAMP/cGMP decreased (P<0.05) in the high-dose carvacrol group. Conclusion In this study, the rat model of stomach-cold and stomach-heat were successfully established by using cold and heat factors. The result showed that carvacrol had a certain inhibitory effect on body mass, material energy metabolism, cyclic nucleotide level, thyroid hormone and gastrointestinal function in rats with stomach-heat, indicating that the drug was cold. Carvacrol′s cold medicinal property could be biologically explained by TRPV1 activation, UCP1 induction, and TRPM8 suppression.

OBJECTIVE: To precise classify sacral meningeal cysts, effective guide minimally invasive neurosurgery and postoperative personalized rehabilitation by multiple dimensions radiographic reconstruction MRI. METHODS: From March to December 2021, based on the original 3D-fast imaging employing steadystate acquisition (FIESTA) scanning sequence, 92 patients with sacral meningeal cysts were pre-operatively evaluated by multiple dimensional reconstruction MRI. The shape of nerve root and the leakage of cyst were reconstructed according to the direction of nerve root or leakage track showed on original MRI scans. Sacral canal cysts were accurately classified as including nerve root and without nerve root, so as to accurately design the incision of skin and formulate corresponding open range of the posterior wall of the sacral canal. Under the microscope intraoperation, the shape of the nerve roots inside cysts or leakage track of the cysts without nerve roots were verified and explored. After the reinforcement and shaping operation, several reexaminations of multiple dimensional reconstruction MRI were performed to understand the deformation of the nerve root and hydrops in the operation cavity, so as to formulate a persona-lized rehabilitation plan for the patients. RESULTS: Among the 92 patients with sacral mengingeal cyst, 58 (63.0%) cysts with nerve root cyst, 29 (31.5%) cysts without nerve root cyst, and 5 (5.4%) cysts with mixed sacral canal cyst. In 58 patients with nerve root cysts, the accuracy of preoperative clinical classification on MRI image reached 96.6% (56/58) through confirmation by operating microscope. Only 2 cases of large single cyst with nerve root on the head of cyst were mistaken for without nerve root type. In 29 patients with sacral cyst without nerve root, the accuracy of preoperative image reached 100% through confirmation by operating microscope. The accuracy of judging the internal nerve root and leakage of 12 cases with recurrent sacral cyst was also 100%. Two cases of delayed postoperative hydrops were found one month after operation. After rehabilitation treatment by moxibustion and bathing, the hydrops disappeared 4-6 months after operation. CONCLUSION Multiple dimensional reconstruction MRI can precisely make clinical classification of sacral meningeal cysts before operation, guide minimally invasive neurosurgery effectively, and improve the rehabilitation effect.
Humans ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Sacrum/surgery* ; Adult ; Middle Aged ; Imaging, Three-Dimensional/methods* ; Cysts/rehabilitation* ; Aged ; Adolescent ; Young Adult ; Spinal Nerve Roots/diagnostic imaging* ; Minimally Invasive Surgical Procedures ; Neurosurgical Procedures/methods*

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

With the gradual development and popularization of extracorporeal membrane oxygenation (ECMO) in China, some prefecture-level medical institutions in China have carried out and formed their own pre-hospital extracorporeal cardiopulmonary resuscitation (ECPR) model. Although the development levels of various prefecture-level cities are uneven and the start times vary, at present, the prefecture-level hospitals in China generally go through the development process of ECMO-in-hospital ECPR-pre-hospital ECPR-professional medical recovery center. Among them, in-hospital ECPR has the advantages of timely resuscitation, guaranteed quality of resuscitation, and fast activation speed of the ECPR team, and currently has a high success rate, with a low proportion of patients with neurological complications. However, pre-hospital ECPR is more challenging, requiring the coordination between pre-hospital and in-hospital emergency forces, multidisciplinary cooperation, and the quality of resuscitation before ECPR cannot be fully guaranteed, the long duration of patient's low perfusion, and other factors make the survival rate of patients without neurological damage obviously lower than that of in-hospital ECPR. China has a large population base, and comprehensive domestic and foreign data show that there should be no less than several million cases of out-of-hospital cardiac arrest under the age of 60 every year, so there is much to be done to improve the survival rate of pre-hospital ECPR. Pre-hospital ECPR is a project of concentrated resources and technology, which has high requirements for the multidisciplinary diagnosis and treatment capabilities of medical institutions. The optimization of the implementation process of in-hospital and pre-hospital ECPR teams, the advancement of the timing of ECPR intervention, the selection of patients, the support and construction of multidisciplinary diagnosis and treatment capabilities after ECPR, and the management of related complications and risk factors are closely related to the prognosis of ECPR patients. The recoverability of the brain and heart is currently the key factor restricting the further improvement of the survival rate of patients after ECPR. Considering that the recovery of neurological function mainly depends on the duration of the early low perfusion, the in-hospital treatment after the implementation of ECPR is mainly the low-temperature brain protection strategy, the effect of which is still controversial, so the recovery of cardiac function is the key that seriously restricts the survival of patients after ECPR in addition to neurological prognosis. The recoverability of the heart after ECPR can be implemented from multiple angles: the research on pathophysiological issues such as the matching of the heart itself after the implementation of ECPR, and the matching between the heart and ECMO, and the proposal of corresponding countermeasures will help to improve the survival rate of patients after ECPR. The large population and the potential salvageable population make the development of ECPR technology in China's tertiary hospitals urgent and necessary, with challenges and opportunities coexisting.
Humans ; Cardiopulmonary Resuscitation/methods* ; China ; Extracorporeal Membrane Oxygenation/methods* ; Emergency Medical Services ; Risk Factors ; Prognosis

Liver cancer imposes a substantial global disease burden.Hepatocellular carcinoma(HCC),as the primary pathological type of primary liver cancer,accounts for approximately 90％of all cases.As a minimally invasive treatment,thermal ablation causes minimal impact on liver function and trauma,serving as the first-line treatment option for early-stage HCC patients unsuit-able for surgical resection.However,clinical data indicate that 5-year recurrence rate of HCC pa-tients after thermal ablation treatment is as high as 50％～70％,and incomplete ablation remains a core factor leading to recurrence.Therefore,exploring and optimizing complete ablation strategies has become a critical direction for improving the efficacy of thermal ablation in HCC and enhanc-ing long-term survival rates of patients.This paper systematically reviews the current applications of thermal ablation in HCC treatment and focuses on discussing key technologies and strategies for achieving complete ablation,with the aim of providing theoretical foundations and technical refer-ences for improving the complete ablation rate of thermal ablation in clinical practice and formu-lating personalized diagnosis and treatment plans.

Objective:To construct a model of mitochondria-related genes (Mito-RGs) in hepatocellular carcinoma (HCC), and predict the immune, prognostic and therapeutic characteristics of HCC based on the model, so as to provide a new idea for the diagnosis and treatment of HCC.Methods:The expression profiles of HCC and corresponding clinical information were obtained from the Cancer Genome Atlas (TCGA) database. Univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate Cox regression were used to construct a prognostic model of HCC based on Mito-RGs, and the International Cancer Genome Consortium-Liver Cancer-RIKEN-Japan ICGC-LIRI-JP dataset were used for validation. GO and KEGG analyses were performed to investigate the signaling pathways enriched for differentially expressed genes in the high- and low-risk groups. Immune infiltration was assessed using CIBERSORT. Single-cell data were used to study the proportion of immune cells in high- and low-risk groups of HCC samples and the relationship with cell proliferation. Cellminer was used to assess the relationship between risk score models and drug sensitivity.Results:A risk-prognostic model of HCC containing seven Mito-RGs ( DTYMK, ACADS, HMGCS2, CYP27A1, TOMM40L, STOM, and AKR1B10) was constructed. High-risk HCC patients had a worse prognosis. Genes upregulated in the high- and low-risk groups of differentially expressed genes were enriched in cell cycle and metabolism-related pathways. Single-cell data showed higher proportions of CD8 + T cells, macrophages and monocytes, and proliferating cells in the high-risk group. CIBERSORT analysis suggested that Treg cells and M0 macrophages were more abundant in the high-risk group, whereas CD8 + T cells and CD4 + memory T cells were less abundant. Patients in the high-risk group were more sensitive to myeloid cell leukemia sequence 1 inhibitor, vincristine, phosphatidylinositol kinase beta subunit inhibitor, and aurora kinase A, while trametinib, selumetinib, extracellular regulated protein kinase, and mitogen-activated extracellular signal-regulated kinase were more effective in the low-risk group. Conclusion:The constructed Mito-RGs model is capable of providing a more accurate assessment of the prognosis and the degree of immune cell infiltration in HCC patients.

Objective:To investigate the analgesic effect of Opisthoplatia orientalis Burm. polypeptides (OOBP) on postherpetic neuralgia (PHN) induced by resiniferatoxin (RTX) in rat models, and its effect on the phosphatase and tensin homologue deleted on chromosome ten (PTEN) -induced kinase 1/Parkin (PINK1/Parkin) signaling pathway. Methods:Thirty-two special pathogen-free rats were randomly divided into 2 groups: a blank control group ( n = 8) receiving intraperitoneal injections of physiological saline (0.20 mg/kg) , and a model group ( n = 24) receiving intraperitoneal injections of RTX (0.20 mg/kg) to establish the PHN rat model. The rats' paw withdrawal mechanical threshold (PWMT) was measured on days 1, 4, 7, and 10 after RTX injections. After 10 days of RTX treatment, rat models were randomly assigned to 3 subgroups: PHN group, OOBP group, and gabapentin group, with 8 rats in each group. The OOBP group and gabapentin group were gavaged with OOBP (equivalent to 0.9 g raw drug per kg) and gabapentin (27 mg/kg) respectively, while the PHN group and control group were gavaged with physiological saline. All treatments lasted for 3 weeks, during which PWMT was continuously monitored. One hour after the final dose, rats were sacrificed, and spinal cord tissues and serum samples were collected. Hematoxylin-eosin (HE) staining was performed to observe spinal pathological changes, enzyme-linked immunosorbent assay (ELISA) to detect serum levels of interleukin-10 (IL-10) , tumor necrosis factor-α (TNF-α) , β-endorphin (β-EP) , and calcitonin gene-related peptide (CGRP) , and Western blot analysis to determine the expression of PINK1, Parkin, and ubiquitin-binding protein P62 in rat spinal cord tissues. The entropy weight method was applied to comprehensively evaluate the effect of OOBP on the above cytokines, proteins and other pharmacodynamic indicators in rat models of PHN. Results:From day 1 to day 10 after modeling, PWMT values in the model group were significantly lower than those in the blank control group (all P < 0.05) , and also significantly lower than baseline values prior to modeling (all P < 0.05) . Histopathological analysis of rat spinal cord tissues showed less pathological changes (such as Nissl body swelling and neuronal necrosis) but more normal Nissl bodies in both the gabapentin group and OOBP group compared with the PHN group. ELISA revealed significantly decreased serum levels of TNF-α and CGRP but significantly increased serum levels of β-EP and IL-10 in the OOBP group compared with the PHN group (all P < 0.05) . Western blot analysis showed that expression levels of PINK1 and Parkin were significantly lower in the gabapentin group (0.441 ± 0.061, 0.597 ± 0.180, respectively) and the OOBP group (0.666 ± 0.117, 0.481 ± 0.073, respectively) than in the PHN group (1.033 ± 0.085, 1.088 ± 0.040, respectively, all P < 0.05) ; in contrast, the P62 expression significantly increased in the gabapentin group (0.810 ± 0.086) and OOBP group (0.902 ± 0.153) compared with the PHN group (0.543 ± 0.082, both P < 0.05) . The entropy weight analysis showed that the comprehensive scores were 0.222 and 0.229 in the OOBP group and the gabapentin group respectively, suggesting a greater overall therapeutic effect of OOBP. Conclusion:OOBP may exert analgesic effects in rat models of PHN by downregulating the expression of inflammatory factors and pain-related factors and modulating the PINK1/Parkin signaling pathway, thereby inhibiting mitochondrial autophagy in spinal neurons and reducing inflammatory responses.