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.

OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction

Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.

This article presents a case report of right vocal cord paralysis resulting from herpes simplex virus infection in an older adult. The patient initially presented with fever, blisters on the lips and right cheek, followed by the gradual onset of hoarseness and difficulty in swallowing. Laryngoscopy revealed fixation of the right vocal cord while the left vocal cord exhibited normal movement. A high level of herpes simplex virus type 1 IgM antibody was detected during the disease progression. Treatment involving mid-dose glucocorticoid and methylcobalamin neurotrophic therapy, swallowing and vocal rehabilitation training, as well as enteral nutrition support, led to alleviation of hoarseness and improved ability to drink water in small sips. Follow-up laryngoscopy indicated partial restoration of movement in the right vocal cord. The article not only outlines the diagnosis and treatment of this case but also reviews relevant literature to broaden clinicians' knowledge of viral-induced vocal cord paralysis in the elderly. It also emphasizes the importance of a geriatric interdisciplinary team in managing complex diseases in older patients.

[Objective] To investigate the effects of fluoride on kallikrein-4 (KLK4) and cell apoptosis as well as the possible mechanisms in ALC cells. [Methods] ALC cells were treated with different concentrations of fluoride for 24 and 48 hours. The effects on cell viability, cell cycle and cell apoptosis were detected using CCK-8, flow cytometry and hoechst 33342, respectively. KLK4 expression was detected by qRT-PCR and Western blotting, and the protein expressions of glucose-regulated protein 78 (GRP78), p-eukaryotic initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) were detected by Western blotting. [Results] The results showed that the expression of KLK4 was significantly reduced after treatment with 1.0 and 2.0 mmol/L NaF for 24 and 48 hours (P<0.05). The difference was statistically significant in cell activity between 2.0 mmol/L NaF treatment group and the control group (P<0.05). The G0/G1 phase cells significantly reduced and the S phase cells significantly increased after treatment with 0.1 and 1.0 mmol/L NaF for 24 hours (P<0.05), while the G0/G1 phase cells significantly increased and the S phase cells significantly reduced in the 2.0 mmol/L NaF treatment cells (P<0.05). The G0/G1 phase cells significantly increased and G2/M phase cells significantly reduced after treatment with 2.0 mmol/L NaF for 48 hours (P<0.05). With the increase of NaF treatment concentration, the number of bright blue cells gradually increased, and the percentage of apoptosis also increased successively. Except for the cells treated with 0.1 mmol/L NaF for 24 hours, the apoptosis rate of the other fluoride treatment groups was statistically significant compared with the control group (P<0.05). The expressions of GRP78 and p-eIF2α were significantly increased after treatment with 0.1, 1.0, and 2.0 mmol/L NaF for 24 hours (P<0.05). The expressions of ATF4 and CHOP were significantly increased after treatment with 1.0 and 2.0 mmol/L NaF for 24 hours (P<0.05). The expressions of ATF4 and CHOP were significantly increased after treatment with 0.1, 1.0, and 2.0 mmol/L NaF for 48 hours (P<0.05). [Conclusion] Sodium fluoride may result in inhibition of KLK4 expression and abnormal cell growth, possibly by inducing GRP78 expression and activating eIF2α/ATF4/CHOP signaling pathway in ALC ameloblasts.

Objective:To evaluate the effect of exogenous interleukin-18 (IL-18) binding protein (IL-18BP) on sepsis-associated lung injury and the role of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes in rats.Methods:This study was performed in two parts. Experiment Ⅰ Thirty-six SPF-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200 g, were allocated into 3 groups ( n=12 each) using a random number table method: sham operation group (S group), sepsis-associated lung injury group (SLI group), and sepsis-associated lung injury+ IL-18BP group (SI group). The rat model of sepsis-associated lung injury was developed using cecal ligation and puncture. The rats in group S underwent laparotomy without the subsequent ligation and puncture procedures. IL-18BP 1.5 mg/kg was intraperitoneally injected immediately after surgery in group SI. Experiment Ⅱ The aforementioned 36 rats were allocated into 3 groups ( n=12 each) using a random number table method: sepsis-associated lung injury + IL-18BP + vehicle group (SIV group), sepsis-associated lung injury + IL-18BP + MCC950 group (SIM group), and sepsis-associated lung injury + IL-18BP + nigericin group (SIN group). In SIV group, SIM group and SIN group, solvent, MCC950 (NLRP3 inhibitor, 5 mg/kg) and nigerin (NLRP3 agonist, 2 mg/kg) were intraperitoneally injected at 30 min before surgery respectively, and IL-18BP 1.5 mg/kg was intraperitoneally injected after operation. HE staining was used to observe the lung injury at 24 h after operation. The left lung tissues were obtained for calculation of the wet/dry weight (W/D) ratio. The concentrations of IL-18 and IL-18BP in broncho-alveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay. The percentage of NLRP3 positive cells in lung tissues was detected by immunofluorescence. The expression of IL-18, IL-18BP, cl-caspase-1 and gasdermin D (GSDMD) in lung tissues was detected by Western blot. Results:Experiment Ⅰ Compared with group S, the injury score of lung tissues, W/D ratio, concentrations of IL-18 and IL-18BP in BALF, and percentage of NLRP3 positive cells were significantly increased, and the expression of IL-18, IL-18BP, cl-caspase-1 and N-GSDMD was up-regulated in group SLI ( P<0.05). Compared with group SLI, the injury score of lung tissues, W/D ratio, concentrations of IL-18 and IL-18BP in BALF, and percentage of NLRP3 positive cells were significantly decreased, the expression of IL-18, cl-caspase-1 and N-GSDMD was down-regulated, and the expression of IL-18BP was up-regulated in group SI ( P<0.05). Experiment Ⅱ Compared with group SIV, the injury score of lung tissues, W/D ratio, concentrations of IL-18 in BALF, and percentage of NLRP3 positive cells were significantly decreased, and the expression of IL-18, cl-caspase-1 and N-GSDMD was down-regulated in group SIM, and the injury score of lung tissues, W/D ratio, concentrations of IL-18 in BALF, and percentage of NLRP3 positive cells were significantly increased, and the expression of IL-18, cl-caspase-1 and N-GSDMD was up-regulated in group SIN ( P<0.05). Conclusions:Exogenous IL-18BP can reduce sepsis-associated lung injury, and the mechanism is related to inhibition of activation of NLRP3 inflammasomes in rats.

The emergence of high virulent mutant strains of infectious bursal disease virus(IBDV)becomes a serious threat to the poultry industry.However,the live attenuated IBDV vaccine can potentially revert to a virulent strain.Therefore,it is a necessary to develop safe and effective IB-DV-associated vaccines.The construction of a recombinant Marek's disease(MD)vaccine strain,CVI988,expressing the IBDV VP2 protein,can protect against disease induced by both IBDV and Marek's disease virus(MDV).Here,the IBDV-VP2 gene was integrated into the UL55 locus of CVI988 by bacterial artificial chromosome(BAC)technique,resulting in the recombinant virus CVI988 BAC-VP2.The recombinant virus was characterized by PCR,IFA and subsequently the bi-ological properties of the recombinant virus were investigated.The results showed that the recom-binant virus CVI988 BAC-VP2 was successfully rescued.The VP2 protein stably expressed in chick-en embryo fibroblasts(CEF).The growth kinetics and plague size assays showed that there was comparable replication ability between recombinant virus and parental virus.This study provides the basis for the development of a low-cost vaccine against both IBDV and MDV infections.

Objective To investigate the relationship between serum survivin,adenosine triphosphate bind-ing cassette transporter Al(ABCA1)and poor coronary collateral circulation(CCC)in patients with single coronary artery occlusion in acute myocardial infarction(AMI).Methods A total of 155 patients with single coronary artery occlusion in AMI admitted to Handan Fist Hospital from May 2021 to May 2023 were selected as the study objects,and were divided into poor CCC group(n=80)and good CCC group(n=75)according to their CCC status.Serum survivin and ABCA1 levels were compared between the two groups,univariate and multivariate Logistic regression models were used to analyze the influencing factors of poor CCC,and the effi-cacy of serum survivin and ABCA1 in predicting poor CCC was analyzed by receiver operating characteristic curve.Results Compared with good CCC group,serum survivin and ABCA1 in poor CCC group were signifi-cantly decreased,and the difference was statistically significant(P＜0.05).Compared with good CCC group,Gensini score,creatinine kinase isoenzyme-MB(CK-MB),Killip heart function grade≥Ⅱ and history of hy-pertension in poor CCC group were significantly increased,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression model showed that high Gensini score,high CK-MB,Killip heart function grade≥Ⅱ and history of hypertension were risk factors for poor CCC(P＜0.05),while high sur-vivin and high ABCA1 were protective factors(P＜0.05).The area under the curve,sensitivity and specificity of the two indexes combined to predict poor CCC were 0.949,90.70％and 92.52％,which were significantly better than the single detection.Conclusion Serum survivin and ABCA1 are closely relate to poor CCC in pa-tients with single coronary artery occlusion in AMI,the lower the serum levels of survivin and ABCA1,the greater the risk of poor CCC,the combine detection of the two has a high predictive value for poor CCC in pa-tients with single coronary artery occlusion in AMI.

ObjectiveTo explore the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements of macroangiopathy in patients with type 2 diabetes mellitus （T2DM） and the key elements of occurrence， development and progression of disease. MethodsA multicenter cross-sectional study was conducted to enroll 445 T2DM patients from five hospitals， and according to the presence or absence of macroangiopathy， the patients were divided into a T2DM group （120 cases） and a diabetic macroangiopathy （DM） group （325 cases）. Patients in DM group were divided into grade Ⅰ， Ⅱ， Ⅲ and Ⅳ according to the peripheral vascular color Doppler ultrasound results and the vascular anomalies classification standard. The general data including gender， age， duration of T2DM and body mass index （BMI） were collected， and the data of four examinations were obtained for syndrome differentiation. According to the diagnostic criteria of TCM syndrome elements， the patients can be divided into 9 patterns including qi deficiency， blood deficiency， yin deficiency， yang deficiency， qi stagnation， blood stasis， excess heat， and excess cold. The general data and distribution of TCM syndrome elements were compared between the two groups. The distribution of TCM syndrome elements in different vascular anomalies grades in the DM group was analyzed. Logistic regression analysis was used to explore the influence of various TCM syndrome elements on the occurrence of macroangiopathy in T2DM. ResultsThere was no significant difference in gender and BMI between groups （P＞0.05）. The age and duration of diabetes in the DM group were older and longer than those in the T2DM group （P＜0.01）. With the increase of age and prolonged course of disease， the severity of diabetic macroangiopathy increases gradually （P＜0.05 or P＜0.01）. There was no significant difference in BMI and course of disease among the different TCM syndrome elements （P＞0.05）. The average age of patients with blood stasis syndrome was the oldest （P＜0.05）. There was significant difference in gender distribution between the excess heat syndrome and yin deficiency syndrome （P＜0.05）. A total of 240 TCM syndrome elements were extracted from the T2DM group， while 731 TCM syndrome elements extracted from the DM group. The top two high-frequency syndrome elements in the two groups were qi deficiency and yin deficiency， with a frequency of larger than 50%. The distribution of phlegm-damp syndrome and blood-stasis syndrome were significantly higher in the DM group than in the T2DM group （P＜0.01）. There were significant differences in the distribution of qi deficiency syndrome， yin deficiency syndrome， phlegm-damp syndrome， blood stasis syndrome， and excess heat syndrome among different grades of vascular anomalies （P＜0.01）； qi deficiency and yin deficiency were both high-frequency TCM syndrome elements in patients at grades 0 to Ⅲ； phlegm-damp syndrome increased in frequency with the progression of the disease from grades 0 to Ⅳ， and the frequency of blood stasis syndrome showed an overall upward trend. The frequency of phlegm-dampness syndrome increased from grades 0 to Ⅳ with the progression of the disease， and the frequency of blood stasis syndrome showed an overall upward trend. Logistic regression analysis showed that phlegm-damp syndrome and blood stasis syndrome were important TCM syndrome elements related to the vascular anomalies degree of macrovascular disease in T2DM （P＜0.05 or P＜0.01）. ConclusionQi deficiency and yin deficiency are the basic TCM syndrome elements throughout the whole process of T2DM and diabetic macrovascular disease. Phlegm-damp and blood stasis are related to the degree of vascular anomalies in diabetic macrovascular disease and are the key TCM syndrome elements in the progression of macroangiopathy in T2DM.