Based on the modern understanding that lipid metabolism disorders mediate tumor microenvironmental imbalance in esophageal carcinoma， this paper proposes that failure of spleen and kidney warming and internal accumulation of phlegm-toxin constitute the core pathogenesis of esophageal carcinoma. Deficiency of spleen and kidney yang qi serves as the root cause， while impaired transformation and transportation of lipids and the accumulation of phlegm-toxin represent the superficial manifestations. Phlegm originates from the transformation of lipids， while toxin arises from and attaches to phlegm. Their interaction forms a sticky and persistent pathological state that runs throughout the entire disease process. The evolution of pathogenesis follows a dynamic and progressive pattern. In the early stage， failure of spleen and kidney warming and dysfunction of lipid metabolism mediate abnormalities in a lipid-enriched microenvironment； in the middle stage， lipid turbidity condenses into phlegm， and phlegm-toxin stasis promotes the formation of an inflammatory and hypercoagulable microenvironment； in the late stage， dysfunction of the sanjiao （三焦） warming function and impaired qi transformation lead to an imbalance in the hypoxic and metabolically dysfunctional microenvironment. Accordingly， a staged therapeutic approach is proposed， including warming the kidney and strengthening the spleen， transforming phlegm and resolving toxin， and warming and unblocking the sanjiao. By regulating lipid metabolism to restore tumor microenvironmental homeostasis， this approach provides a new theore-tical perspective and practical strategy for the intervention of esophageal cancer progression through traditional Chinese medicine.

Based on the modern understanding that lipid metabolism disorders mediate tumor microenvironmental imbalance in esophageal carcinoma， this paper proposes that failure of spleen and kidney warming and internal accumulation of phlegm-toxin constitute the core pathogenesis of esophageal carcinoma. Deficiency of spleen and kidney yang qi serves as the root cause， while impaired transformation and transportation of lipids and the accumulation of phlegm-toxin represent the superficial manifestations. Phlegm originates from the transformation of lipids， while toxin arises from and attaches to phlegm. Their interaction forms a sticky and persistent pathological state that runs throughout the entire disease process. The evolution of pathogenesis follows a dynamic and progressive pattern. In the early stage， failure of spleen and kidney warming and dysfunction of lipid metabolism mediate abnormalities in a lipid-enriched microenvironment； in the middle stage， lipid turbidity condenses into phlegm， and phlegm-toxin stasis promotes the formation of an inflammatory and hypercoagulable microenvironment； in the late stage， dysfunction of the sanjiao （三焦） warming function and impaired qi transformation lead to an imbalance in the hypoxic and metabolically dysfunctional microenvironment. Accordingly， a staged therapeutic approach is proposed， including warming the kidney and strengthening the spleen， transforming phlegm and resolving toxin， and warming and unblocking the sanjiao. By regulating lipid metabolism to restore tumor microenvironmental homeostasis， this approach provides a new theore-tical perspective and practical strategy for the intervention of esophageal cancer progression through traditional Chinese medicine.

Objective To investigate the association between single nucleotide polymorphisms (SNPs) in the nicotinamide adenine dinucleotide phosphate-oxidase (NOX) 2 and NOX4 genes and susceptibility to noise-induced hearing loss (NIHL). Methods A total of 439 noise-exposed workers were recruited using a convenience sampling method. Based on pure-tone air conduction hearing threshold tests, participants were categorized into normal hearing, mild hearing loss, and moderate hearing loss groups, with 147, 154, 138 individuals, respectively. Peripheral venous blood samples of the workers were collected for DNA extraction. Genotyping of nine SNPs loci in NOX2 and NOX4 genes was performed using multiplex polymerase chain reaction, single-base extension, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results A total of seven of the nine SNPs loci conformed to Hardy-Weinberg equilibrium among the workers in the normal hearing group (all P>0.05). There was no significant difference in the genotype distribution or allele frequencies for these seven SNPs loci among workers in these three groups (all P>0.05). Ordinal logistic regression analysis showed that, after adjusting for confounders including age, sex, cumulative noise exposure, smoking, alcohol consumption, and earplug use, individuals carrying the GG genotype at rs200522762 had a lower risk of NIHL compared with those carrying the TT genotype under the codominant model (P<0.05). In the recessive model, individuals carrying the GG genotype at the rs200522762 locus had a lower risk than those carrying the GT+TT genotypes (P<0.05). Polymorphisms at the other six SNPs loci were not associated with NIHL risk (all P>0.05). Conclusion The NOX4 rs200522762 polymorphism is associated with susceptibility to NIHL.

The Department of Thoracic Surgery of Shanghai Chest Hospital has performed esophageal function testing for over 30 years, being the only department of its kind in China with this capability. The pressure testing and 24-hour pH/impedance monitoring of the esophagus is of great help to assist in the diagnosis and treatment of benign and malignant esophageal diseases related to it. Thanks to the esophageal function test, in addition to the routine various endoscopic anti-reflux procedures, our hospital has taken the lead in China in recent years to carry out a series of clinical and research work for benign esophageal diseases, such as the development of magnetic ring, double nedoscopic combination and new anti-reflux endoscopic techniques. In recent years, we have carried out high-resolution esophageal manometry and 24-hour pH/impedance monitoring for patients with interstitial pneumonia and pulmonary fibrosis suspected to be caused by gastroesophageal acid reflux. We can better assess the correlation between gastroesophageal reflux and pulmonary fibrosis, and to provide the different clinical treatments and even surgical interventions. The Bravo capsule is used more often in the United States, and it has obvious advantages over traditional approach for acid measurement. We strongly call for the collaboration between industry and academic institutions in this field, and the development of our own related products with independent intellectual property rights.

ObjectiveTo clarify the repair effect of Mume Fructus on the intestinal mucosal epithelial barrier in the mouse model of inflammatory bowel disease （IBD） and explore the repair mechanism. MethodsThirty-six male C57BL/6 mice were randomly assigned into six groups： normal， model， low-， medium-， and high-dose （200， 400， and 800 mg·kg^-1） Mume Fructus， and sulfasalazine （300 mg·kg^-1）. Except the normal group， the rest groups had free access to 2% dextran sulfate sodium （DSS） solution for seven days to establish the IBD model， followed by a seven-day drug intervention. The body weight change and disease activity index （DAI） were recorded. After the last administration， spleen and colon tissue samples were collected to analyze the differences in colon length and spleen index. Hematoxylin-eosin staining was used to observe the morphology of the colon tissue. The level of diamine oxidase （DAO） in the serum was measured by the DAO assay kit. Immunohistochemistry was employed to determine the expression of tight junction proteins such as Claudin-1， Occludin， and zonula occludens-1 （ZO-1） in the colon tissue. Real-time PCR was performed to measure the mRNA levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the colon tissue. Finally， Western blot was employed to determine the protein levels of mitogen-activated protein kinase kinase （MEK）， extracellular signal-regulated kinase （ERK）， phosphorylated （p）-MEK， and phosphorylated ERK in the colon tissue. ResultsCompared with the normal group， the model group exhibited decreases in body weight and colon length （P<0.01）， increases in DAI， spleen index， and serum DAO level （P<0.01）， damaged colonic epithelium and goblet cells， and obvious infiltration of inflammatory cells. In addition， the model group exhibited higher positive expression of Claudin-1， Occludin， and ZO-1 （P<0.01）， higher mRNA levels of TNF-α and IL-1β （P<0.01）， and higher protein levels of p-MEK and p-ERK （P<0.05， P<0.01） than the normal group. However， sulfasalazine and three doses of Mume Fructus markedly decreased the body weight and DAI （P<0.05）， recovered the colon length and spleen index， alleviated colon tissue damage， lowered the level of DAO in the serum （P<0.01）， and down-regulated the mRNA levels of TNF-α and IL-1β （P<0.01） and the protein levels of p-MEK and p-ERK （P<0.05）. Sulfasalazine and low- and medium-dose Mume Fructus increased the positive expression of Occludin， Claudin-1， and ZO-1 （P<0.05， P<0.01）. Furthermore， high-dose Mume Fructus elevated the protein expression of Occludin （P<0.05）. ConclusionMume Fructus can restore the expression of intestinal epithelial tight junction proteins by inhibiting the phosphorylation of proteins in the MEK/ERK signaling pathway and down-regulating the levels of TNF-α and IL-1β， thus repairing the intestinal mucosal barrier in the mouse model of IBD.

ObjectiveTo investigate the modulating effect of modified Wumeiwan （MWMW） on the ulcerative colitis （UC）-associated intestinal helper T cell 17 （Th17）/regulatory T cell （Treg） balance and intestinal flora by using a human flora-associated model of UC patients with dampness-heat obstruction syndrome， thus providing a new idea for the UC-related research and therapeutic strategies. MethodsThe 24 male C57BL/6J mice were randomized into normal control， model， and MWMW groups （n=8）. Model and MWMW groups were first treated with an antibiotic cocktail （vancomycin， 0.1 g·kg^-1； neomycin sulfate， 0.2 g·kg^-1； ampicillin， 0.2 g·kg^-1； metronidazole， 0.2 g·kg^-1） for 21 days. At the end of antibiotic treatment， the gavage of fecal microbiota suspension from UC patients with dampness-heat obstruction syndrome was started at a dose of 0.2 mL·d^-1 for 19 consecutive days， by which a human flora-associated model of UC was obtained. The MWMW group was administrated daily with MWMW liquid （12.5 g·kg^-1）， while the normal control and model groups were administrated by gavage with an equal amount of sterile water for 7 consecutive days. The symptoms of dampness-heat obstruction were observed. The colon length and spleen index were measured and calculated， and the proportions of Th17 and Treg cells were detected by flow assay. The intestinal flora was analyzed by 16S rRNA high-throughput sequencing. ResultsCompared with the normal control group， the model group showed shortened colon （P<0.05） and increased spleen index （P<0.01）. Compared with the model group， the MWMW group showed prolonged colon （P<0.01） and decreased spleen index （P<0.05）. After the intervention of MWMW， the Th17 proportion and Th17/Treg ratio in the colon decreased （P<0.01）， and the proportion of Treg cells increased （P<0.05）. The number of species and alpha and beta diversity of intestinal flora in mice were regulated by MWMW （P<0.05）. In terms of intestinal flora composition， MWMW increased the relative abundance of several phyla （Firmicutes， Proteobacteria， Fusobacteriota， Actinobacteriota， and Gemmatimonadota）， the genus Bacteroides， and two species （Bacteroides thetaiotaomicron and B. fragilis） in model mice. Moreover， Spearman's correlation analysis showed that the relative abundance of B. thetaiotaomicron and B. fragilis were negatively correlated with the Th17 level （P<0.05）. In addition， the above changes in intestinal flora caused the changes in microbial genes involved in 14 pathways， such as glycolysis， amino acid degradation， inorganic nutrient metabolism， biosynthesis of pyrimidine deoxyribonucleotides， antibiotic resistance， and degradation of polysaccharides. ConclusionsThe human flora-associated model successfully simulated the changes （marked by a decrease in the abundance of Bacteroides） of intestinal flora in UC patients with dampness-heat obstruction syndrome. MWMW can enrich the abundance of beneficial bacteria such as B. thetaiotaomicron and B. fragilis and promote the synergistic intestinal immune modulation with the metabolic functions centered on glycolysis， amino acid metabolism， and nucleotide synthesis through bacterial polysaccharide utilization sites to reduce the Th17/Treg ratio， thereby exerting a protective effect on UC.

OBJECTIVE: To propose a machine learning-based method for predicting the trajectories during manual acupuncture manipulation (MAM), aiming to improve the precision and consistency of acupuncture practitioner' operation and provide the real-time suggestions on MAM error correction. METHODS: Computer vision technology was used to analyze the hand micromotion when holding needle during acupuncture, and provide a three-dimensional coordinate description method of the index finger joints of the holding hand. Focusing on the 4 typical motions of MAM, a machine learning-based MAM trajectory predictive model was designed. By integrating the changes of phalangeal joint angle and hand skeletal information of acupuncture practitioner, the motion trajectory of the index finger joint was predicted accurately. Besides, the roles of machine learning-based MAM trajectory predictive model in the skill transmission of acupuncture manipulation were verified by stratified randomized controlled trial. RESULTS: The performance of MAM trajectory predictive model, based on the long short-term memory network (LSTM), obtained the highest stability and precision, up to 98%. The learning effect was improved when the model applied to the skill transmission of acupuncture manipulation. CONCLUSION The machine learning-based MAM predictive model provides acupuncture practitioner with precise action prediction and feedback. It is valuable and significant for the inheritance and error correction of manual operation of acupuncture.
Humans ; Acupuncture Therapy/instrumentation* ; Machine Learning ; Adult ; Male ; Female

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Based on the pharmacokinetics theory, this study investigated the pharmacokinetic characteristics of albiflorin, paeoniflorin, wogonoside, and wogonin in normal and febrile rats and summarized absorption and elimination rules of Dayuanyin in them to provide reference for further development and clinical application of Dayuanyin. Blood samples were taken from the fundus venous plexus of normal and model rats after intragastric administration of Dayuanyin at different time points. The concentration of each substance in blood was determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS) technique at different time points. DAS 2.0, a piece of pharmacokinetics software, was used to calculate the pharmacokinetic parameters of each component. The results show that the 4 components had good linear relationship in their respective ranges, and the results of methodological investigation met the requirements. The pharmacokinetic parameters of C_(max), T_(max), t_(1/2), AUC_(0-t), AUC_(0-∞), and MRT_(0-t) were calculated by the DAS 2.0 non-compartmental model. Compared with those in the normal group, C_(max) and AUC_(0-t) of the 4 components in the model group were significantly increased. There were significant differences in the pharmacokinetic characteristics between the normal and model groups, suggesting that the absorption and elimination of Dayuanyin may be affected by the changes of internal environment of the body in different physiological states.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Fever/metabolism* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Glucosides/pharmacokinetics* ; Monoterpenes