Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Objective This study aimed to investigate the seasonal variation of mosquitoes in Yantai, Shandong Province, and provide a scientific basis for mosquito and mosquito-borne disease control. Methods From March to November for each of the years between 2020 and 2023, adult mosquitoes were collected from different habitats, including parks, hospitals, urban residential areas, rural households and livestock sheds, in 13 counties of Yantai City using a mosquito trap lamp method, among which, female mosquitoes were separated and identified, and the numbers were counted. We used the circular distribution method to analyze the temporal distribution characteristics of mosquito density. Results The γ values obtained for mosquitoes in Yantai from 2020 to 2023, the distribution of mosquitoes in different habitats, and dominant mosquito species in different months showed strong seasonality, with values ranging from 0.7461 to 0.8531(P ＜ 0.05). The peak period of seasonal variation in mosquitoes occurred from June 28thto September 13th, with August 5thbeing identified as the peak day. The peak periods of seasonal variation in mosquitoes in residential areas, parks, hospitals, peasant households, and animals sheds were observed from June 24thto September 14th, June 25thto September 10th, June 22ndto September 12th, July 1stto September 9th, and July 2ndto September 17th, respectively, with corresponding peak days on August 4th,3rd, 2nd, 5th, and 9th, respectively. The peak periods of Culex pipiens pallens, Aedes albopictus, and Anopheles sinensis were from June 26thto September 11th, June 28thto September 17th, and July 12thto September 17th, respectively, with corresponding peak days on August 3rd,7th, and 14th, respectively. Conclusions Our findings in this study revealed that the peak of mosquito activity in Yantai was concentrated in early August, with a peak period extending from June 28thto September 13th, and there were differences between different habitats(with peak periods for rural households and livestock sheds occurring later than those in residential areas, parks, and hospitals). Moreover, with respect to the mosquito species, populations of Cx. pipiens pallens and Ae. albopictus peaked earlier than those of An. sinensis. Based on these findings, we recommend that city-wide mosquito control work should commence in late June, and include appropriate early prevention and control measures for key habitats, such as livestock sheds, and dominant mosquito species, such as Cx. pipiens pallens, to minimize the density of mosquito vectors and the risk of disease transmission.

ObjectiveTo investigate the incidence and relevant factors of visual acuity abnormalities in preschool children undergoing kindergarten entrance physical examinations in Shannan City, Xizang, in 2022, so as to formulate policies for protecting children’s visual acuity and provide a basis for optimizing the children’s health service system in this region. MethodsA cross sectional study was conducted among the children undergoing kindergarten entrance physical examinations in Shannan City in 2022. A diopter examination was performed for these children, and a questionnaire survey was administered to their caregivers. Additionally, factors affecting children’s visual acuity abnormalities were analyzed using the χ² test and binary logistic regression analysis. ResultsA total of 759 children were included in the analysis, with an incidence rate for visual acuity abnormalities of 11.20%. Univariate analysis showed that statistically significant differences were observed in the incidence rate for visual acuity abnormalities among preschool children in terms of different family monthly income (χ²=17.395, P<0.001), father’s education level (χ²=5.133, P=0.023), postnatal vitamin A and D supplementation (χ²=9.575, P=0.008), and feeding method within the first 6 months after birth (χ²=9.330, P=0.009). Multivariate analysis results indicated that family monthly income <5 000 yuan (OR=2.599, P=0.003), insufficient postnatal vitamin A and D supplementation (OR=1.912, P=0.011), and formula feeding (OR=2.131, P=0.010) were relevant factors for abnormal visual development in children. ConclusionThe incidence of visual acuity abnormalities in preschool children in Shannan City is slightly higher than that previously reported in other regions of Xizang. The occurrence of visual acuity abnormalities in children is related to factors such as family monthly income, postnatal vitamin A and D supplementation, and feeding method within the first 6 months after birth. Future interventions should be strengthened on the promotion and dissemination of knowledge related to eye use, such as improve parental awareness of eye care, promote timely vitamin A and D supplementation and encourage breast feeding for children after birth, more specifically, attentions need to be focused on the visual acuity problems of children from low-income families to safeguard the visual health in preschool children in Shannan City, Xizang.

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

OBJECTIVE: As an age-related neurodegenerative disease, the prevalence of mild cognitive impairment (MCI) increases with age. Within the framework of traditional Chinese medicine, spleen-kidney deficiency syndrome (SKDS) is recognized as the most frequent MCI subtype. Due to the covert and gradual onset of MCI, in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes. There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS (MCI-SKDS). METHODS: This investigation enrolled 312 elderly individuals diagnosed with MCI, who were randomly distributed into training and test datasets at a 3:1 ratio. Five machine learning methods, including logistic regression (LR), decision tree (DT), naive Bayes (NB), support vector machine (SVM), and gradient boosting (GB), were used to build a diagnostic prediction model for MCI-SKDS. Accuracy, sensitivity, specificity, precision, F1 score, and area under the curve were used to evaluate model performance. Furthermore, the clinical applicability of the model was evaluated through decision curve analysis (DCA). RESULTS: The accuracy, precision, specificity and F1 score of the DT model performed best in the training set (test set), with scores of 0.904 (0.845), 0.875 (0.795), 0.973 (0.875) and 0.973 (0.875). The sensitivity of the training set (test set) of the SVM model performed best among the five models with a score of 0.865 (0.821). The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset. The DCA of all models showed good clinical application value. The study identified ten indicators that were significant predictors of MCI-SKDS. CONCLUSION The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical; the model demonstrates good predictive value and clinical applicability, and the DT model had the best performance. Please cite this article as: Ai YT, Zhou S, Wang M, Zheng TY, Hu H, Wang YC, Li YC, Wang XT, Zhou PJ. Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly. J Integr Med. 2025; 23(4): 390-397.
Humans ; Cognitive Dysfunction/diagnosis* ; Aged ; Male ; Female ; Machine Learning ; Spleen ; Aged, 80 and over ; Kidney ; Medicine, Chinese Traditional

OBJECTIVE: This study aimed to evaluate the relationships of white blood cell (WBC) count, platelet (PLT) count, and PLT-to-WBC ratio (PWR) with muscle mass in Chinese older adults. METHODS: This cross-sectional analysis involved 4,033 Chinese older adults aged ≥ 65 years from the Healthy Ageing and Biomarkers Cohort Study. Muscle mass and total skeletal muscle mass index (TSMI) were measured by bioelectric impedance analysis. WBC, PLT, and PWR were measured using standard methods. Multivariate linear regression was used to examine the associations of WBC count, PLT count, and PWR with TSMI. RESULTS: High WBC count, PLT count, and PWR were associated with low TSMI, with coefficients of -0.0091 (95% confidence interval [ CI]: -0.0142 to -0.0041), -0.0119 (95% CI: -0.0170 to -0.0068), and -0.0051 (95% CI: -0.0102 to -0.0001). The associations between the three inflammatory indices and TSMI were linear. Stratified analyses indicated that the relationship between inflammatory markers and TSMI was more evident in male participants and in individuals aged < 80 years than in their counterparts. CONCLUSION Elevated WBC count, PLT count, and PWR correlated with muscle mass loss. This study highlights the importance of regular monitoring of inflammatory markers as a potential strategy for the screening and management of sarcopenia in older adults.
Humans ; Aged ; Male ; Female ; China ; Leukocyte Count ; Cross-Sectional Studies ; Platelet Count ; Aged, 80 and over ; Muscle, Skeletal/anatomy & histology* ; Independent Living ; Blood Platelets ; Leukocytes ; Sarcopenia

Objective To investigate the clinical characteristics of patients with clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia(PBMAH).Methods A retrospective analysis was performed on the clinical data of 198 patients with Cushing's syndrome caused by PBMAH diagnosed in the First Medical Center of Chinese PLA General Hospital from January 2004 to October 2024.According to clinical manifestations,the patients were classified into clinical type Cushing's syndrome(n=61)and subclinical type Cushing's syndrome(n=137),and the clinical characteristics of the two types were compared.Results The mean age at diagnosis of patients with PBMAH-induced Cushing's syndrome was(53.5±10.4)years,including 118 males and 80 females,with a male-to-female ratio of 1.475:1.Compared with the subclinical type,the clinical type had a higher proportion of females,higher levels of serum cortisol,24-hour urine free cortisol(24 h UFC),and inhibited serum cortisol after low-dose dexamethasone suppression.Additionally,the clinical type had lower plasma ACTH,larger adrenal nodules and a higher risk of surgery(P<0.05)compared with those in subclinical type.The incidences of hypertension,dyslipidemia,obesity,diabetes mellitus,hypokalemia,vitamin D deficiency,osteoporosis,coronary heart disease,and cerebrovascular disease in patients with Cushing's syndrome caused by PBMAH were 87.9%,50.5%,37.1%,36.9%,27.8%,25.9%,18.7%,18.7%and 12.1%,respectively.Among them,compared with subclinical type patients,clinical type patients had higher incidence of hypokalaemia,vitamin D deficiency and osteoporosis(P<0.05),while there were no statistically significant differences in the incidences of other comorbidities between the two types(P>0.05).The results of postoperative follow-up for PBMAH patients showed that the short-term biochemical remission rate of unilateral total adrenalectomy was 41.5%(22/53)and the long-term biochemical remission rate was 32.0%(8/25).The short-term biochemical remission rate of unilateral partial(or nodular)adrenalectomy was 52.9%(9/17),and the long-term biochemical remission rate was 14.3%(1/7).All patients who underwent unilateral total adrenalectomy plus contralateral partial resection developed adrenal insufficiency(3/3),and 1 patient(1/3)relapsed 3.4 years after surgery.Conclusion Clinical and subclinical types of Cushing's syndrome caused by PBMAH have their distinct clinical characteristics.Surgery is an effective treatment for PBMAH,but a certain proportion of patients fail to achieve biochemical remission after non-bilateral total adrenalectomy.

Objective To summarize the clinical characteristics of primary pigmented nodular adrenocortical disease(PPNAD)and provide a reference for its clinical diagnosis and treatment.Methods A retrospective analysis was conducted on the clinical characteristics,laboratory tests,imaging examinations,treatment plans,and follow-up data of 10 PPNAD patients diagnosed and treated at the First Medical Center of Chinese PLA General Hospital from January 2008 to October 2024.Databases including CNKI,Wanfang Data Knowledge Service Platform,and PubMed were searched,and the clinical characteristics of 120 PPNAD patients reported in the literature were summarized in combination with literature reviews.Results The age at diagnosis of the 10 PPNAD patients ranged from 15 to 55 years,with a median age of onset of 21.5 years.Seven patients had the protein kinase A regulatory subunit 1 alpha(PRKAR1A)gene mutations,meeting the diagnosis criteria for Carney syndrome.One patient presented with hypertension only,while the remaining 9 patients showed typical Cushing's syndrome manifestations such as thin skin and moon face,among whom 5 experienced stagnation of height growth.In 7 patients,the adrenocorticotropic hormone(ACTH)levels were<2.2 pmol/L,with the disrupted circadian rhythm of cortisol,and the cortisol levels at midnight ranged from 243.24 to 679.83 pmol/L.None of the patients showed suppression in the low-dose dexamethasone suppression test,and 8 patients had an increase in urinary free cortisol(UFC)after dexamethasone suppression.Adrenal CT showed that 9 patients presented with unilateral adrenal nodules accompanied by contralateral thickening or bilateral adrenal nodular thickening.All 10 patients underwent initial unilateral adrenalectomy,and during follow-up,4 patients experienced symptom recurrence and underwent contralateral adrenalectomy.Most of the 120 patients reported domestically and internationally showed typical Cushing's syndrome manifestations.Surgical resection of the adrenal gland was the main treatment modality.Gene mutations were predominantly in PRKAR1A,with a few in PDE11A and PRKACA.Conclusions PPNAD is more likely to occur in adolescents.Patients with typical Cushing's syndrome manifestations should undergo screening.Imaging manifestations are atypical,and a definitive diagnosis depends on pathological and genetic diagnoses.Bilateral adrenalectomy combined with long-term postoperative hormone replacement therapy is the standard treatment protocol.Patients who undergo early unilateral adrenalectomy require long-term follow-up,with contralateral adrenalectomy performed when necessary.

Objective:To investigate the role and possible mechanism of tripartite motif-containing protein 72 (Trim72) in acute viral myocarditis (AVMC) in mice.Methods:A mouse model of AVMC was established by intraperitoneal injection of Coxsackievirus B3 (CVB3, 2.0 × 10 5 PFU/mouse). Forty mice were randomly divided into the negative control (NC) + phosphate-buffered saline (PBS) group (NC+PBS group), Trim72 overexpression + PBS group (Trim72 + PBS group), NC + CVB3 group, and Trim72 + CVB3 group ( n = 10). Fourteen days before modeling, mice in each group were injected with adeno-associated virus type 9 vector (AAV9) encoding either negative control or Trim72 overexpression (5.0 × 10 11 VG/mouse) via tail vein. Subsequently, PBS or CVB3 was injected intraperitoneally in the PBS and CVB3 groups, respectively. After seven days, the surviving mice were euthanized, and the heart and serum samples were collected. HE and TUNEL staining were used to observe the cardiac pathological changes and cardiomyocyte apoptosis, respectively. The mRNA expression levels of Trim72 and pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in myocardial tissues of each group were detected by RT-qPCR. The protein levels of cTnI, TNF-α, IL-6, and IL-1β in serum were detected by ELISA. The expression levels of Trim72, apoptosis-related proteins (Bax, Bcl-2, Cleaved caspase-3, Caspase-3), TLR4, p-p65, and p65 were detected by Western blot. Results:The protein and mRNA expression levels of Trim72 in myocardial tissues of mice in the NC+CVB3 group were significantly downregulated compared with those in the NC + PBS group ( P<0.05). Compared with the NC + CVB3 group, Trim72 overexpression significantly increased the protein and mRNA expression of Trim72 in myocardial tissues ( P<0.05), ameliorated myocardial inflammatory injury, decreased the apoptotic index of cardiomyocytes ( P<0.05), and reduced the levels of pro-inflammation cytokines TNF-α, IL-6, and IL-1β in the myocardium and serum ( P<0.05). Additionally, Trim72 overexpression also downregulated the protein expression of Bax, Cleaved caspase-3/Caspase-3, TLR4, and p-p65, and upregulated the protein expression of Bcl-2 in myocardial tissues ( P<0.05). There was no significant difference in the indexes of mice between the NC + PBS and Trim72 + PBS groups ( P>0.05). Conclusions:Trim72 overexpression attenuates AVMC in mice by inhibiting myocardial inflammatory injury and apoptotic imbalance, and the mechanism may be related to the negative regulation of the TLR4/NF-κB signaling pathway.