ObjectiveTo investigate the expression changes of the Endophilin A1 （EPA1）-reactive oxygen species （ROS）-NLR family pyrin domain containing 1 （NLRP1） signaling pathway in chronic unpredictable mild stress （CUMS）-induced depression model mice. Methods50 C57BL/6 mice were randomly divided into control group and CUMS model group（n=25）. The model mice received 42 days of CUMS stress exposure， after which behavioral changes were assessed through monitoring body weight， sucrose preference test， forced swim test， tail suspension test， open field test， and elevated plus-maze test. Hematoxylin-Eosin and Nissl staining were used to observe neuronal damage in hippocampal CA1 and CA3 regions. Calcium ion （Ca²⁺） assay kit was used to detect Ca²⁺ levels in the hippocampus. Immunofluorescence was used to detect colocalization of EPA1 and NLRP1 as well as ROS changes in the hippocampus. Transmission electron microscopy was used to observe mitochondrial structure in hippocampal neurons. The expression levels of calcium-activated neutral protease 1 （Calpain-1）， nicotinamide adenine dinucleotide phosphate oxidase 2 （NOX2）， NLRP1 inflammasome， downstream inflammatory proteins， and synapse-associated proteins in the hippocampus of mice was detected by using Western blot. ResultsCompared with the control group， mice in the CUMS model group exhibited depressive-like behavior and hippocampal neuronal damage. The levels of NLRP1 and EPA1 significantly increased in the hippocampus， and both were co-expressed in the cytoplasm and membrane of hippocampal neurons in the CUMS group mice（P<0.01）. Ca²⁺ concentration was elevated（P<0.01）， and the protein levels of Calpain 1 and NOX2 were upregulated（P<0.01）. The average fluorescence intensity of ROS significantly increased， accompanied by structural damage to neuronal mitochondria（P<0.01）. The levels of NLRP1 and its downstream inflammatory proteins significantly increased （P<0.01）， while the expression levels of synapse-associated proteins significantly decreased （P<0.01）. ConclusionEPA1 exhibits abnormal expression changes in CUMS-induced depression model mice， which may be closely associated with ROS generation， NLRP1 inflammasome activation， and the regulation of synaptic protein expression.

Based on the theory of diseased collaterals and the progression pattern of diabetic kidney disease （DKD）， this paper proposes a staged treatment system based on the "three states of kidney collaterals" including collateral distention， collateral bi （痹） and collateral accumulation. In the collateral distention stage， the primary pathogenesis is heat damaging the kidney collaterals and collateral vessel dilation， corresponding to the early state of DKD characterized by hyperfiltration and microalbuminuria； the clearing method is suggested， and Shenling Jiangtang Formula （参苓降糖方） can be used to promote the remission of proteinuria by ameliorating insulin resistance and regulating intestinal microecology. In the collateral bi stage， the core pathogenesis lies in the binding of phlegm and stasis， and the formation of concretions and conglomerations in the kidney collaterals， corresponding to massive proteinuria and the decline of renal function， for which the unblocking method should be taken， using Jinchan Yishen Tongluo Formula （金蝉益肾通络方） and Qingre Xiaozheng Formula （清热消癥方） to alleviate renal pathological damage by regulating the autophagy-lysosome pathway and repairing mitochondrial energy metabolism. The collateral accumulation stage is characterized by the internal retention of turbid toxins and accumulations of concretions in the kidney collaterals， corresponding to renal fibrosis and end-stage renal disease （ESRD）； the dispersion method is suggested， and Yiqi Tongluo Xiezhuo Formula （益气通络泄浊方） and Shenyan Fangshuai Fluid （肾炎防衰液） can be used to inhibit extracellular matrix accumulation and delay the progressive loss of renal function. Collateral deficiency runs through the entire course of the disease and is closely related to cellular senescence and the imbalance of the ubiquitin-proteasome/autophagy system. The concept of the "three states of kidney collaterals" integrates the evolution of traditional Chinese medicine pathogenesis with modern pathological staging， forming a whole-course intervention system of "staging-syndrome differentiation-target-formula"， thereby providing novel insights for prevention and treatment of DKD using integrated traditional Chinese and western medicine.

Based on the typical cases from Case Records as a Guide to Clinical Practice （《临证指南医案》） where YE Tianshi applied the "morning and evening differential treatment"， the main types are summarized as follows. When there is middle-lower interlocking injury， and yin deficiency with wind stirring， the method of restraining and consolidating in the morning can be used to restrict jueyang （厥阳）. For deficiency of the extraordinary vessels and heart-spleen ying （营） impairment， the method of consolidating should be used to raise yang in the morning， while the method of moistening and nourishing ying-yin in the evening is used. For lower jiao （焦） depletion with phlegm turbidity obstructing the orifices， it is recommended to tonify lower jiao in the morning and fortify spleen and dissolve phlegm in the evening. If there is kidney-yin depletion with dampness obstructing the qi， it is suggested to supplement kidney and improve qi reception in the morning， while purify upper jiao in the evening. For deficiency and impairment of the collateral vessels， the method of moistening and nourishing ying-yin in the evening can be used. For heart-spleen qi knot， it is recommended to dissolve phlegm and dispel stasis in the evening. In clinical practice， the same medicinal formula can be used with different methods which change according to the syndrome. Taking Sishen Pills （四神丸） and Yuhu Elixir （玉壶丹） as examples， employing different methods in accordance with the primary and secondary pathomechanisms can help transform complex， multiple pathomechanisms into organized treatment steps， providing ideas for managing complicated syndromes with modern Chinese medicine in clinical practice.

Temporomandibular disorders （TMD） encompass a prevalent group of conditions affecting the masticatory muscles， temporomandibular joint， and associated structures. Currently， it is widely recognized by scholars both domestically and internationally that TMD has a complex etiology and pathogenesis. Most patients present clinically with pain， yet effective treatment options remain limited. In recent years， the role of ion channels in the pathological mechanisms and therapeutic approaches for TMD has garnered increasing attention. This review systematically summarizes the function of ion channels in the management of temporomandibular joint diseases. First， the multifaceted roles of ion channels in treating TMD are examined， including their regulatory effects on TMJ muscle dysfunction， joint structural abnormalities， and TMJ-related pain. Finally， the potential value of ion channel research in TMD therapy is discussed. With advancing research in this field， ion channel-targeted therapies for temporomandibular disorders are expected to achieve new breakthroughs， thereby providing an important theoretical foundation and practical guidance for developing novel clinical treatment strategies.

BACKGROUND:Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor,anti-inflammatory,antioxidant and other aspects.However,its poor water solubility,unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield.Therefore,it is particularly important to optimize the curcumin extraction method.OBJECTIVE:To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process.METHODS:Curcumin was extracted from turmeric by ethanol extraction,ultrasonic extraction,ionic liquid extraction,enzyme extraction,and ionic liquid combined with ultrasonic assisted enzyme extraction.The curcumin extraction yield was detected by high performance liquid chromatography;the best extraction method was determined,and subsequent process optimization experiments were carried out.The curcumin extraction yield was the response value with the type of ionic liquid,reaction temperature,ultrasonic time,liquid-to-solid ratio,ionic liquid concentration,and enzyme-drug mass ratio as parameters.The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment.The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration,chitosan to sodium tripolyphosphate mass ratio,stirring rate,curcumin mass concentration,sodium tripolyphosphate mass concentration,and chitosan mass concentration as parameters,and drug encapsulation efficiency as response value.Curcumin nanoparticles were prepared under the optimal process,and the particle size,polydispersity index,Zata potential value,drug loading,stability,hemolysis rate,and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.RESULTS AND CONCLUSION:(1)Among the five extraction methods,the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest,and this method was selected as the curcumin extraction method for subsequent experiments.The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was:ionic liquid selected 1-hexyl-3-methylimidazolium chloride,reaction temperature 55 ℃,liquid-to-solid ratio 40 mL/g,ultrasound time 57 minutes,ionic liquid concentration 57％,enzyme-drug mass ratio 3.5:10,and the obtained turmeric extraction yield was 3.10％.The optimal preparation process of curcumin nanoparticles was:glacial acetic acid concentration 0.5％,chitosan and sodium tripolyphosphate mass ratio 5.0:1,stirring speed 150 r/min,curcumin mass concentration 2.23 mg/mL,sodium tripolyphosphate mass concentration 1.45 mg/mL,chitosan mass concentration 3.63 mg/mL,and the obtained drug encapsulation efficiency was 90.61％.(2)The drug loading of curcumin nanoparticles was(14.49±0.23)％,the average particle size was(76.95±1.65)nm,the polydispersity coefficient was 0.15±0.02,and the Zata potential value was(32.37±1.46)mV.The curcumin nanoparticles had good stability and blood compatibility,did not induce hemolysis,and had stronger antioxidant capacity in vivo and in vitro than free curcumin.(3)The results show that the process optimization not only solves the problems of low extraction yield,poor solubility,and low bioavailability of curcumin,but also enhances its antioxidant activity in vivo and in vitro.

BACKGROUND:Upper lumbar spinal stenosis is a multifactorial degenerative disorder of the spine.For narrowing of the spinal canal in the upper lumbar region(L1-L4),surgical decision-making is particularly complex.Existing minimally invasive surgeries each have their own advantages and limitations.Currently,there are few reports on biomechanical comparison and finite element analysis of different surgical methods for the treatment of high lumbar spinal stenosis.OBJECTIVE:To analyze the biomechanical impact of endoscopic unilateral laminotomy for bilateral decompression,transforaminal endoscopic lumbar decompression,and cross-overtop decompression in the treatment of upper lumbar spinal stenosis using endoscopy,and to verify the reliability and effectiveness of these three surgical techniques in treating upper lumbar spinal stenosis,providing a biomechanical basis for clinical decision-making.METHODS:The CT images of the lumbar spine of a healthy volunteer were selected,and the finite element model M0 of the normal lumbar L1-L5 segments was established using Mimics,Geomagic,Solid works,and Ansys software.The L2-L3 segment,representing upper lumbar characteristics,was chosen.Based on this model,the surgical models for endoscopic unilateral laminotomy for bilateral decompression(M1),transforaminal endoscopic lumbar decompression(M2),and cross-overtop decompression(M3)were established.Using software,the changes in the range of motion of the entire lumbar segment and the maximum Von Mises stress of the intervertebral discs were simulated and evaluated for each group of models under six loading conditions:flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation.RESULTS AND CONCLUSION:(1)Compared with model MO,the range of motion in M1,M2,and M3 increased under all six conditions,with M1 showing a greater increase.(2)M1 and M2 demonstrated significant increases in range of motion under forward bending,extension,and right rotation,while the increase under other conditions remained below 7％.(3)Compared with model M3,model M1 exhibited slightly increased overall joint range of motion during extension and left bending,while no significant changes were observed in other aspects,and the L1-L5 lumbar segments did not reach an unstable state.(4)In model M1,the maximum Von Mises stress of the intervertebral discs increased most significantly under flexion and extension loading conditions.However,under left lateral bending,right lateral bending,left rotation,and right rotation loading conditions,the increase did not exceed 5％.(5)These findings suggest that due to the sagittal anatomical characteristics of the facet joints,the unilateral laminotomy for bilateral decompression technique,while decompressing,involves resection of more facet joints,which impacts overall segmental stability.The transforaminal endoscopic lumbar decompression technique is suitable for patients with foraminal stenosis but cannot achieve complete decompression for those with severe ventral central stenosis.The Cross-Overtop technique effectively enlarges the volume of the central canal and lateral recess,optimizing decompression,and shows unique advantages in treating upper lumbar spinal stenosis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.

Objective: To systematically analyze the confirmatory positivity of different combinations of HBsAg screening results in blood testing, providing data to support the optimization of blood donor eligibility management. Methods: A retrospective analysis was conducted on blood screening data from 174 266 voluntary blood donor samples at the Chongqing Blood Center between October 2021 and September 2022. Samples with inconsistent results between the two HBsAg enzymelinked immunosorbent assays (ELISA) and individual donor nucleic acid testing (NAT) were confirmed using an electrochemiluminescence immunoassay (ECLIA) and a neutralization test. The detection efficacy of four different HBsAg ELISA reagents was compared using the HBsAg-confirmed positive samples. Results: A total of 767(0.44%) HBV-reactive (HB-sAg and/or HBV DNA reactive) samples were detected. Among them, 344 samples with discordant serological and NAT results were collected, of which 64(18.6%) were confirmed positive by neutralization test. Additionally, 5 samples that were neutralization-negative but double-reactive for HBsAg and HBV DNA were confirmed as positive according to FDA guidance, resulting in a total of 69(20.1%) confirmed HBsAg-positive samples. There were significant differences in the neutralization test confirmation rates among different screening result categories (P<0.05): The group with dual HBsAg reagent reactivity (double reactive) & NAT-negative had the highest confirmation rate (96.9%, 31/32); the group reactive to only reagent 2 (single reactive) had a rate of 25.7% (29/113); while the confirmation rates for samples reactive to only reagent 1 and samples with isolated HBV DNA positivity were extremely low [0(0/34) and 2.4%(4/165), respectively]. The four commercial reagents showed significant differences in their ability to detect confirmed positive samples that were initially single reactive (P<0.05). Conclusion: Given the performance variations among HBsAg screening reagents, thorough performance verification is essential before implementation. When NAT is negative, dual HBsAg reactivity in screening can serve as a basis for confirming infection and directly deferring blood donors. However, confirming infection in donors with single HBsAg reactivity is more challenging, necessitating supplementary tests to rule out infection risk.

OBJECTIVE To investigate the correlation of component content with colorimetric values during the roasting process of Ziziphus jujuba ， and to provide criteria for discriminating the roasting degree of Z. jujuba . METHODS Samples were prepared by dry stir-frying for different roasting times. The eight main components in raw Z. jujuba and the samples stir-fried for different roasting times-namely adenosine， magnoflorine， jujuboside A， spinosin， 6-feruloylspinosin， betulinic acid， oleic acid， and linoleic acid-were quantitativel y analyzed using ultra-performance liquid chromatography. The chromaticity values were determined using a UV spectrophotometer. The correlation and differences between the chromaticity values of Z. jujuba at different roasting times and their components content were analyzed by Pearson correlation analysis， linear regression analysis， principal component analysis （PCA） ， cluster heatmap analysis （CHA）， and partial least squares discriminant analysis （PLS-DA） to clarify the processing endpoint. RESULTS As the roasting time increased， the contents of linoleic acid and oleic acid decreased， while the contents of other components exhibited an increasing trend. Concurrently， the colorimetric value L* and E*ab were observed to decline， whereas the a* value demonstrated a gradual increase. Pearson correlation analysis revealed that L* and E*ab exhibited a significant negative correlation with the contents of adenosine， spinosin， 6-feruloylspinosin， jujuboside A， betulinic acid and magnoflorine （ P ＜0.05）. The results of linear regression analysis indicate that the content of six components, including adenosine， in the medicinal material can be preliminarily predicted by analyzing the colorimetric values of Z. jujuba powder. PCA and CHA successfully classified raw and stir-fried samples. The PLS-DA results indicated that L*， E*ab， a*， linoleic acid content， and oleic acid content were the main parameters that differentiated the color and quality of Z. jujuba at different roasting times. After frying for 9 to 10 minutes， the colorimetric values L* and E*ab decreased to their minimum values and stabilized， while a* remained consistently high with little variation；simultaneously， the concentrations of the six major components， excluding linoleic acid and oleic acid， reached their peak levels. CONCLUSIONS A significant correlation between the colorimetric values of Z. jujuba and the contents of six components， including adenosine， is confirmed. The optimal roasting time range is determined to be 9-10 minutes. Furthermore， the colorimetric value-component content correlation analysis method established in this study proved to be practical and applicable for discriminating the roasting degree of Z. jujuba .

Objective To investigate the alleviating effect of jujuboside B (JuB) on acute epilepsy in mice and its protective effect on hippocampal neurons. Methods An in vitro epilepsy model was established by stimulating primary hippocampal neurons with cyclothiazide (CTZ). Spontaneous epileptiform discharge was recorded using patch clamp technique. An acute epilepsy model was induced in adult male C57BL/6 mice by intraperitoneal injecting pentylenetetrazol (PTZ) following pretreatment with JuB, and severity of epilepsy was recorded. Mice were euthanized and brain tissues were collected 24 hours after model establishment. The expression levels of mitoptosis related proteins in the hippocampus were detected by Western blotting. Neuronal damage in the hippocampal CA1 and CA3 regions was observed using pathological staining. Results JuB reduced the frequency of CTZ-induced epileptiform discharges (P＜0.001). Pretreatment with 30 mg/kg and 50 mg/kg JuB decreased the maximal behavioral seizure score and prolonged the latency to Racine stage Ⅲ seizures in PTZ-induced epileptic mice (P＜0.001). Compared with the PTZ group, JuB treatment downregulated Bax protein level (P＜0.01) and upregulated Bcl-2 protein level (P＜0.05) in acute epileptic mice. Furthermore, JuB protected neuronal viability in the hippocampal CA1 (P＜0.05) and CA3 (P＜0.01) regions, and ameliorated pathological morphological changes including cellular disarray, unclear boundaries, pyknosis, fragmentation, and dissolution. Conclusions JuB exhibits antiepileptic effects both in vivo and in vitro. It exerts potential antiepileptic effects by inhibiting mitoptosis and attenuating neuronal damage in the hippocampus in an acute epilepsy model.