ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective: To investigate the epidemiological characteristics and spatial-temporal clustering of varicella in Changchun City from 2020 to 2024, so as to provide the evidence for formulating local varicella prevention and control measures. Methods: The individual case data of varicella were collected through the Surveillance and Reporting Management System of the Chinese Disease Prevention and Control Information System in Changchun City from 2020 to 2024. Descriptive epidemiological methods were used to analyze the population ,regional, and temporal distribution. Spatial autocorrelation and spatio-temporal scanning analyses were used to identify the spatial-temporal clustering characteristics. Results: A total of 8 850 varicella cases were reported in Changchun City from 2020 to 2024, with an average annual incidence of 19.64/105. There were 4 929 male cases and 3 921 female cases, with a male-to-female ratio of 1.26∶1. The age was mainly 0-<20 years (6 649 cases, 75.13%), and students were the predominant occupation (6 036 cases, 68.20%). The top three counties (cities, districts) with the highest number of cases were Chaoyang District (1 944 cases), Gongzhuling City (1 054 cases) and Nanguan District (987 cases), accounting for 45.03%. The peak incidence periods were from April to June and from October to December, with 2 166 and 4 226 cases, accounting for 24.47% and 47.75%, respectively. Spatial autocorrelation analysis showed that spatial clustering existed from 2020 to 2024. The high-high clustering areas were mainly some townships (streets) in Chaoyang District, Nanguan District, Changchun New District and Jingyue District. Spatio-temporal scanning analysis identified 6 high-risk clustering areas. The class Ⅰ clustering area was Nanhu Street in Chaoyang District, with the clustering period from September 2020 to February 2022. Conclusions Varicella cases in Changchun City were mainly males and students aged 0-<20 years from 2020 to 2024. The peak incidence was mainly in winter. Chaoyang District was a high-risk area, with obvious spatial-temporal clustering.

ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide. Coupled with the substantial workload, the clinical management of lung cancer is challenged by the critical need to efficiently and accurately process increasingly complex medical information. In recent years, large language models (LLMs) technology has undergone explosive development, demonstrating unique advantages in handling complex medical data by leveraging its powerful natural language processing capabilities, and its application value in the field of lung cancer diagnosis and treatment is continuously increasing. The paper systematically analyzes that the exceptional potential of LLMs in lung cancer auxiliary diagnosis, tumor feature extraction, automatic staging, progression/outcome analysis, treatment recommendations, medical documentation generation, and patient education. However, they face critical technical and ethical challenges including inconsistent performance in complex integrated decision-making (e.g., TNM staging, personalized treatment suggestions) and "black box" opacity issues, along with dilemmas such as training data biases, model hallucinations, data privacy concerns, and cross-lingual adaptation challenges ("data colonization"). Future directions should prioritize constructing high-quality multimodal corpora specific to lung cancer, developing interpretable and compliant specialized models, and achieving seamless integration with existing clinical workflows. Through dual drivers of technological innovation and ethical standardization, LLMs should be prudently advanced for holistic lung cancer management processes, ultimately promoting efficient, standardized, and personalized diagnosis and treatment practices.

ObjectiveTo investigate the therapeutic effect and mechanism of modified Chunzetang on bladder fibrosis and detrusor function in rats with neurogenic bladder urinary retention induced by spinal cord injury. MethodsIn this study， an improved Hassan Shaker spinal cord transection method was used to establish a model of neurogenic bladder urinary retention induced by spinal cord injury， and rats with a spinal cord injury behavior score of 0 were selected for follow-up experiments. The selected rats were randomly divided into a model group （normal saline gavage）， low-dose traditional Chinese medicine （TCM） group （gavage of 14.4 g·kg^-1 modified Chunzetang）， high-dose TCM group （gavage of 28.8 g·kg^-1 modified Chunzetang）， positive drug group ［intraperitoneal injection of 0.05 g·kg^-1 nuclear transcription factor-κB （NF-κB） inhibitor pyrrolidine dithiocarbamate （PDTC）］， and combination group （intraperitoneal injection of 0.05 g·kg^-1 PDTC + gavage of 28.8 g·kg^-1 modified Chunzetang）. The rats in these groups were administrated with corresponding drugs once a day for four weeks. The BL-420s biofunction acquisition system was used in the experiment to calculate the urodynamic indexes， and the isolated bladder was quickly weighed. The detrusor traction experiment was used to record the minimum bladder contraction tension and frequency in each group. The pathological morphology and tissue fibrosis of detrusor in each group observed by Hematoxycin-eosin （HE） staining and Masson staining were compared. The expression level of α-smooth muscle actin （α-SMA） was detected by immunohistochemistry. Western blot was used to detect the protein expression of NF-κB p65， nuclear transcription factor-κB suppressor protein α （IκBα）， transforming growth factor-β₁ （TGF-β₁）， type Ⅰ collagen （ColⅠ）， and type Ⅲ collagen （ColⅢ） in bladder tissue of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the changes in serum levels of IL-6， IL-1β， and TNF-α. ResultsCompared with that in the sham operation group， the pressure at the urinary leakage point in the model group decreased （P<0.01）， and the bladder mass， bladder contractile tension， maximum bladder capacity， and bladder compliance increased （P<0.05，P<0.01）. HE staining showed that the arrangement of bladder epithelial cells was disordered， and the pathological manifestations such as mucosa and myometria neutrophil infiltration were obvious. The lamina propria structure was destroyed， and the muscle fiber arrangement was disordered. The interstitial widening and tissue edema were obvious. Masson staining showed that the bladder wall of the model group had more collagen fiber deposition， and the degree of detrusor fibrosis was more severe. The content of detrusor in the visual field was reduced. At the same time， the protein expressions of NF-κB p65， TGF-β₁， IκBα， ColⅠ， and ColⅢ in bladder tissue of rats in the model group were significantly increased （P<0.01）， and the serum levels of IL-6， IL-1β， and TNF-α were significantly increased （P<0.05）. Compared with that in the model group， the pressure at the urinary leakage point in the modified Chunzetang and positive drug groups was increased （P<0.05）， and the wet bladder weight， minimum bladder contractile tension， maximum bladder capacity， and bladder compliance were restored （P<0.05， P<0.01）. HE and Masson showed that the bladder epithelial cells were relatively neatly arranged， and the structure of the bladder lamina propria was relatively stable. The detrusor bundles were arranged in an orderly manner， and the interstitium was narrow. The degree of tissue edema was relatively low， and the degree of bladder detrusor fibrosis in the modified Chunzetang and positive drug groups was reduced， while the degree of bladder detrusor fibrosis in the positive drug group and combination groups was not obvious. The results of Western blot showed that the expression of NF-κB p65， IκBα， TGF-β₁， ColⅠ， and ColⅢ in bladder tissue， as well as the serum levels of IL-6， IL-1β， and TNF-α in modified Chunzetang and positive drug groups were significantly lower， and the expression of bladder tissue-related proteins and the serum levels of IL-6， IL-1β， and TNF-α in the TCM groups decreased significantly with the increase in dose （P<0.05）. The results of immunohistochemistry suggested that modified Chunzetang could fully affect the expression of α-SMA in bladder tissue. ConclusionModified Chunzetang can inhibit collagen deposition in bladder tissue of rats with urinary retention induced by spinal cord injury， delay the occurrence and development of bladder fibrosis， and protect the normal contractile function of bladder detrusor， and its mechanism may be related to inhibiting the NF-κB/TGF-β₁ signaling pathway， reducing the production of NF-κB p65， IκBα， TGF-β₁， ColⅠ， ColⅢ， and other related proteins， and protecting the muscle strength of detrusor.

To summarize Professor DING Ying's clinical experience in treating children's IgA nephropathy from the perspective of "wind-induced water turbidity". It is believed that the core pathogenesis of IgA nephropathy in children is the wind stimμlating water to become turbidity， and the basic treatment principles are to eliminate wind and settle viscera， and to remove turbidity and drain water. For those with the syndrome of wind-heat invading the lungs and injury to blood collaterals， modified Yinqiao Powder （银翘散） combined with Xiaoji Decoction （小蓟饮子） could be used； for those with dampness-heat in Sanjiao， heavy dampness and light heat pattern， modified Sanren Decoction （三仁汤） combined with Bazheng Powder （八正散） could be used； for those with lung-spleen qi deficiency and kidney essence depletion pattern， modified Buzhong Yiqi Decoction （补中益气汤） combined with Wuzi Yanzong Pill （五子衍宗丸） could be used； for those with deficiency of both qi and yin， kidney deficiency with stasis pattern， self-prescribed Yishen Huazhuo Formula （益肾化浊方） could be used. Meanwhile on the basis of pattern identification and treatment， rattan-type herbs could be combined in use in order to unblock the meridians and collaterals.

The 2024 World Conference on Lung Cancer (WCLC) and the European Society for Medical Oncology (ESMO) Annual Meeting, two of the most prestigious events in oncology, have concluded sequentially. As the most authoritative annual gatherings in lung cancer and the entire oncology field, the WCLC and ESMO conferences brought together top oncology experts and scientists from around the world to share, discuss, and publish the latest cutting-edge advancements in oncology. In both conferences, lung cancer immunotherapy remained a hot topic of considerable interest. This article aims to summarize and discuss the important research progress on perioperative immunotherapy for non-small cell lung cancer reported at the two conferences.