Based on advancements in modern medical research regarding the intricate connection between the endocrine and exocrine functions of the pancreas， as well as the relationship between pancreatic functions and traditional Chinese medicine （TCM） spleen system， this paper discussed the categorization of the pancreas. It is proposed that the pancreas is neither a true zang organ nor a fu organ， but possessed the attributes of an extraordinary fu-organ and can be classified under the spleen. The spleen governs transportation and transformation， ascent of the clear and dispersion of essence， which encompasses the endocrine and exocrine functions， and pancreatic enzymes and glucose-regulating hormones form the material basis for the spleen's function of dispersing essence. Diseases of the pancreas exhibit characteristics of both zang-organ deficiency and fu-organ excess， so treatment should simultaneously supplement zang-organ disease and regulate fu-organ disease when pancreas showing endocrine and exocrine co-morbidities， with focus on restoring the pancreas （spleen）'s dispersing essence function. Therapeutic strategies include supplementing spleen qi， nourishing spleen yin to strengthen spleen earth， unblocking spleen collaterals， raising spleen yang， and removing spleen turbidity to support the spleen's dispersing essence function， so as to replenish the essential qi of zang-fu organs， ensure their distribution throughout the body， and improve the endocrine and exocrine functions of the pancreas.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

Objective:To summarize the clinical characteristics and management experience of complications in patients with cervical necrotizing fasciitis （CNF） with or without descending necrotizing mediastinitis （DNM）, in order to provide a basis for optimizing diagnosis and treatment strategies. Methods:A retrospective analysis was conducted on the clinical data of 31 patients diagnosed with CNF and DNM at Shandong Provincial Hospital Affiliated to Shandong First Medical University between October 2019 and March 2024. A comprehensive evaluation was performed based on the patients' clinical characteristics, metagenomic next-generation sequencing （mNGS） pathogen detection results, imaging assessments, surgical interventions, management approaches for specific complications, and prognostic outcomes. Results:Among the 31 patients, 10 had severe diabetes mellitus. Etiological analysis was summarized as follows: 5 cases were odontogenic, 3 were of tonsillar origin, 3 were due to endogenous esophageal injury, 2 were due to exogenous cervical trauma, 2 originated from a congenital branchial cleft fistula, and 16 cases had an unknown etiology. Among them, 29 patients underwent surgery via an external cervical approach, 1 patient underwent surgery via an intraoral approach, and 1 patient received ultrasound-guided puncture and drainage therapy. Ultimately, 29 patients were cured and discharged （including 1 patient who experienced two instances of major neck vessel rupture and successfully underwent two interventional embolization procedures for hemostasis）; 2 patients died after failed rescue efforts due to concurrent sepsis and multiple organ dysfunction. The treatment success rate was 93%, and the mortality rate was 7%. In this cohort of CNF and DNM cases, only a minority had a clearly identified odontogenic cause; although the etiology was unknown in most cases, imaging consistently showed oropharyngeal lymph node necrosis, suggesting a possible pharyngeal origin of infection in adults. The mNGS pathogen profile was predominantly Gram-positive bacteria, accompanied by anaerobic bacilli and fungi. Conclusion:CNF and DNM are severe and rapidly progressive conditions that can lead to life-threatening complications within hours. Timely recognition can reduce unnecessary examinations and expedite treatment.
Humans ; Retrospective Studies ; Fasciitis, Necrotizing/therapy* ; Mediastinitis/complications* ; Neck/pathology* ; Male ; Female ; Middle Aged ; Adult ; Aged ; Prognosis

This study investigates the neuroprotective potential of extracellular vesicles (EVs) delivering quercetin-3-O-β-d-glucuronic acid (QG-EVs) in cerebral ischemia-reperfusion injury (CIRI). Targeted brain delivery of QG-EVs was confirmed, with neuron cells identified as pivotal in modulating CIRI through single-cell RNA sequencing (scRNA-seq). Activating transcription factor 4 (Atf4) was highlighted as a critical regulatory factor, and in vitro studies revealed that silencing Atf4 diminished the neuroprotective effects of QG-EVs, increasing oxidative stress levels and neuronal apoptosis. In a CIRI mouse model, the knockdown of Atf4 attenuated the protective outcomes provided by QG-EVs, further affirming the role of Atf4 in mediating neuroprotection. Behavioral assessments and protein analysis showed that QG-EVs significantly reduced neuronal damage and pro-apoptotic markers, while improving neurological function via Atf4 upregulation. The outcomes hint at the potential of QG-EVs as a beneficial therapeutic modality to mitigate neuronal damage in CIRI by enhancing Atf4 expression, highlighting its potential for improving ischemic stroke outcomes.

Objective:To assess the efficacy of silicone earplugs in protecting workers exposed to noise in a typical manufacturing environment, and to provide training interventions for workers who do not achieve the anticipated noise reduction levels, as well as examining the spectral characteristics of earplug attenuation.Methods:From June to August 2022, a total of 294 noise-exposed workers in two manufacturing enterprises equipped with the same type of earplug were studied by cluster sampling method, by conducting questionnaire surveys, collecting data, fitting tests, and providing trainings, the current noise exposure levels of workers in the industry as well as the perception about the earplug were understood. Additionally, the attenuation before and after intervention in workplace were measured, the spectral characteristics of noise reduction were were described and compared.Results:The percentage of workers with Personal Attenuation Rating (PAR) of 0 is 32.7% (96/294), and the baseline pass rates are all below 60%. There were no significant differences in pass rates based on gender, age, noise exposure, education level, or cognition of earplug effectiveness. After adjusting the way that earplugs are worn or changing the type of earplugs, all workers were able to meet their noise reduction requirements. The median PAR improvement for both companies is above 10 dB. The noise attenuation of the earplug vary with frequency, with lower attenuation at 4 000 Hz and higher attenuation at 8 000 Hz, showing some deviation from the nominal values.Conclusion:The difference between the actual sound attenuation value of earplugs and the nominal value is related to the noise frequency. When using silicone earplugs, attention should be paid to the spectral composition of the noise in the workplace.

Objective:To assess the efficacy of silicone earplugs in protecting workers exposed to noise in a typical manufacturing environment, and to provide training interventions for workers who do not achieve the anticipated noise reduction levels, as well as examining the spectral characteristics of earplug attenuation.Methods:From June to August 2022, a total of 294 noise-exposed workers in two manufacturing enterprises equipped with the same type of earplug were studied by cluster sampling method, by conducting questionnaire surveys, collecting data, fitting tests, and providing trainings, the current noise exposure levels of workers in the industry as well as the perception about the earplug were understood. Additionally, the attenuation before and after intervention in workplace were measured, the spectral characteristics of noise reduction were were described and compared.Results:The percentage of workers with Personal Attenuation Rating (PAR) of 0 is 32.7% (96/294), and the baseline pass rates are all below 60%. There were no significant differences in pass rates based on gender, age, noise exposure, education level, or cognition of earplug effectiveness. After adjusting the way that earplugs are worn or changing the type of earplugs, all workers were able to meet their noise reduction requirements. The median PAR improvement for both companies is above 10 dB. The noise attenuation of the earplug vary with frequency, with lower attenuation at 4 000 Hz and higher attenuation at 8 000 Hz, showing some deviation from the nominal values.Conclusion:The difference between the actual sound attenuation value of earplugs and the nominal value is related to the noise frequency. When using silicone earplugs, attention should be paid to the spectral composition of the noise in the workplace.

Objective We aimed to study the protective effect of total glucosides of paeony (TGP) on chemical liver injury with pattern of liver yin deficiency in rats and determine whether it exerts these effects through the phosphoinositide 3-kinase(PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway.Methods Forty male Sprague-Dawley rats were randomly divided into the following four groups: (i) the blank group, (ii) the model group, (iii) the Yiguan Jian group, and (iv) the TGP group (10 rats per group). For 6 weeks, rats in all groups except for the blank group were injected intraperitoneally with 20％ carbon tetrachloride olive oil solution and were given thyroid tablets (30mg/kg) by gavage in order to establish the model of chemical liver injury with pattern of liver yin deficiency. During the modeling period, rats in the blank and model groups were gavaged daily with distilled water, while rats in the Yiguan Jian group and the TGP group were gavaged with 635mg/kg of Yiguan Jian decoction and 50mg/kg of TGP suspension, respectively. During the administration period, the body weight and rectal temperature of rats were measured every 2 weeks. After the administration, 24-hour food intake, 24-hour water intake, and moisture capacity in tongue surface were recorded. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1Ra) contents were measured by ELISA and the cAMP/cGMP ratio was calculated. Changes in the serum levels of alanine aminotransferase (ALT), alanine transaminase (AST), gamma-glutamyl transpeptidase (γ-GT), alkaline phosphatase (ALP), total bilirubin (TBIL), and total bile acids (TBA) were detected using colorimetric method. Masson staining was performed to observe the degree of liver fibrosis and to calculate the relative collagen area. Real-time PCR and Western blotting were conducted to determine the PI3K, AKT, and mTOR mRNA and protein expression levels in rat liver.Results Compared with the blank group, rats in the model group had a lower body weight at weeks 2, 4, and 6, a higher rectal temperature at weeks 2, 4, and 6, and a higher 24-hour food intake; the cAMP level was elevated, the cGMP level was decreased, and the cAMP/cGMP ratio was elevated; the contents of IL-1, IL-6, and TNF-α were elevated, and the contents of IL-10 and IL-1Ra were decreased; ALT, AST, γ-GT, ALP, TBIL, and TBA levels were elevated; the percentage of collagen area in the liver was increased; and the mRNA and protein phosphorylation levels of PI3K, AKT, and mTOR were elevated ( P<0.05). Compared with the model group, rats in the TGP group showed a decrease in rectal temperature at weeks 2, 4, and 6, a decrease in 24-hour food intake and water intake, and an increase in the moisture capacity in tongue surface; rats in the Yiguan Jian and TGP groups showed a decrease in cAMP, an increase in cGMP, and a decrease in the cAMP/cGMP, the contents of IL-1, IL-6, and TNF-α were decreased and the content of IL-10 was increased, the percentage of collagen area in the liver was decreased; ALT, AST, γ-GT, ALP, and TBIL levels were decreased in the TGP group, and PI3K, AKT, and mTOR were downregulated at the mRNA and protein levels(P<0.05).Conclusion TGP has a good protective effect on chemical liver injury with pattern of liver yin deficiency in rats. TGP may regulate the balance of yin and yang by inhibiting the PI3K/AKT/mTOR pathway, reducing the secretion of pro-inflammatory cytokines, and increasing the release of anti-inflammatory cytokines.

Objective:To analyze the protective effect of neurotracheal catheter monitoring on recurrent laryngeal nerve in patients with bilateral cervical lymph node dissection of thyroid cancer.Methods:The clinical data of 92 patients undergoing bilateral cervical lymph node dissection for thyroid cancer at the First People's Hospital of Shangqiu from Jul 2019 to Aug 2022 were retrospectively analyzed. Patients were divided into control group (routine exposure, 52 cases) and study group (intraoperative neurotrachatic catheter monitoring, 40 cases) The general data, perioperative indicators, parathyroid function, vocal cord function, voice disorder index, quality of life and postoperative complications were compared between the two groups.Results:The intraoperative blood loss in the study group [(12.3±3.3) ml] was less than that in the control group [(16.9±4.0) ml]. The exposure time [(8.7±2.6) min], operation time [(4.0±0.8) h] and postoperative hospitalization time [(3.2±0.9) d] were shorter than those of control group [(14.4±3.6) min, (4.5±1.2) h, (5.7±1.3) d] ( t=5.770, 8.391, 2.387, 10.853, all P<0.05);Amplitude perturbation (4.85%± 0.58%), fundamental frequency perturbation (0.28%±0.17%), standardized noise energy [(-20.3±4.4) dB], VHI-10 score [(1.6±0.5) score], Quality of life scale for cancer patients 1 month after surgery the TG-V4 score [(43.7±4.8) points] was lower than that of control group [(3.05%±0.54%), (0.42%±0.16%), (-14.6±3.3) dB, (3.3±0.4) points, (50.4±5.6) points]. The harmonic noise ratio [(24.9±4.1) dB] was higher than that of the control group [(20.3±4.4) dB] ( t=10.446, 4.049, 7.036, 19.076, 6.116, 5.144, all P<0.001);The incidence of postoperative complications in the study group (8%) was lower than that in the control group (23%) ( χ2=4.020, P=0.045). Conclusion:Neurotracheal catheter monitoring during bilateral cervical lymph node dissection for thyroid cancer can improve vocal cord function, reduce recurrent laryngeal nerve injury, reduce voice disturbance and improve quality of life.

Objective To explore the association between R611H(G/A,rs734312)variation of WFS1 gene and early-onset type 2 diabetes mellitus(T2DM).Methods A total of 181 Chinese patients with early-onset T2DM(T2DM group)and 196 non-diabetic controls(NC group)were enrolled in this study.The rs734312 variation was detected by PCR-direct sequencing.Genotypic and allelic frequencies of rs734312 and clinical variables were compared and analyzed between the two groups.Results Compared with the NC group,the frequencies of AA genotype and A allele in R611H(G→A)variation were significantly elevated in the early-onset T2DM group,AA vs GA+GG(OR 1.720,95%CI 1.100～2.680,P<0.05).A vs G(OR 1.500,95%CI 1.020～2.220,P<0.05).The remarkable differences of frequencies of genotype and allele in rs734312(G/A)were observed between Asians(China,Japan and Korea)and Caucasians(Denmark,Britain,Spain,France and Russia,P<0.01 for each).Compared with AA genotype,fasting and 2 hours postprandial insulin(FIns and 2 hIns)as well as HOMA-β were significantly rise in GG+GA genotype carriers of early-onset T2DM group(P<0.05).Conclusions The a allele of rs734312 in WFS1 may be a risk factor for early-onset T2DM in Chinese population,and the variation might be a potential genetic marker for predicting the islet β-cell dysfunction in early-onset T2DM in Chinese population.