Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM＋EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P＜0.01); UCM＋EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P＜0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P＜0.05); ventricular remodeling was alleviated (P＜0.05), though there was no significant improvement in systolic function in UCM＋EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P＜0.01); the myocardial pathology improved with reduced collagen deposition in UCM＋EMPA group (P＜0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P＜0.01), while myocardial hypertrophy was alleviated in UCM＋EMPA group (P＜0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P＜0.05), but downregulated in UCM＋EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM＋EMPA group (P＜0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.

Objective:To investigate the reference intervals of serum uric acid levels in normal-weight children and analyze the factors influencing these levels.Methods:In this cross-sectional study, clinical data were collected from 7 910 normal-weight children, aged 1 month to 15 years, who underwent health check-ups at the Children′s Hospital of Zhejiang University School of Medicine between August 2013 and August 2023. Data included sex, age, pubertal signs, blood pressure, and serum uric acid levels. The participants were categorized into 4 age groups: 1-<12 months, 1-<6 years, 6-<11 years, and 11-<16 years, and were further analyzed by sex. The P5 and P95 percentiles of uric acid values were defined as the lower and upper limits of the reference interval, respectively. Correlation analysis and partial correlation analysis were used to assess the relationship between uric acid and other variables such as age, body mass index Z value, and Tanner stage. Multivariate linear regression was used to compare uric acid levels across gender and age groups, respectively. Results:Among the 7 910 children, the distribution across age groups was as follows: 562 (317 boys) in 1-<12 months, 4 120 (2 366 boys) in 1-<6 years, 2 357 (1 432 boys) in 6-<11 years, and 871 (536 boys) in 11-<16 years, the uric acid levels in boys were significantly higher than those in girls ( P<0.05). Uric acid levels exhibited a positive correlation with age ( r=0.47 , 0.20, both P<0.001), and a weak positive correlation with BMI Z-scores(both r=0.11, P<0.001). Among participants aged 6-<11 years and 11-<16 years, uric acid levels in boys were positively correlated with Tanner stage ( r=0.10, 0.27, both P<0.05), but no significant correlation was observed in girls (all P>0.05). The uric acid levels were significantly higher in boys than in girls in the 1-<12 months, 1-<6 years and 11-<16 years age groups (all P<0.05), but no significant gender difference was found in the 6-<11 years groups ( P>0.05). Uric acid levels exhibited statistically significant variations among age groups ( P<0.001). The reference intervals of uric acid values were as follows in 1-<12 months age group, 157-335 μmol/L for boys and 160-315 μmol/L for girls; in 1-<6 years age group, 180-359 μmol/L for boys and 180-355 μmol/L for girls; in 6-<11 years group, 190-375 μmol/L; in 11-<16 years age group, 237-480 μmol/L for boys and 218-410 μmol/L for girls. Conclusions:Reference intervals for uric acid varying significantly across different pediatric age groups. Sex, and pubertal development status are closely related to uric acid levels.

Vaccination is a crucial strategy for the prevention and control of infectious diseases. Virus-like particles (VLPs), composed of structural proteins, have garnered significant attention as a novel type of vaccine due to their excellent safety and immunogenicity. However, similar to most vaccine antigens, VLPs exhibit insufficient thermal stability, which not only restricts the widespread application of vaccines but also increases the risk of vaccine inactivation. This study aims to enhance the stability and shelf life of VLPs derived from type A foot-and-mouth disease virus (FMDV) by employing vacuum freeze-drying technology. The optimal lyoprotectant formulation was determined through single-factor and combinatorial screening. Subsequently, the correlation between the immunogenicity of the freeze-dried vaccine and the content of FMDV VLPs was evaluated via a mouse model. The stability of FMDV VLPs before and after freeze-drying was further assessed by storing them at 4, 25, and 37 ℃ for varying time periods. Results indicated that the lyoprotectant formulation No.1, composed of 7.5% trehalose, 0.1% Tween 80, 50 mmol/L glycine, 1% sodium glutamate, and 3% polyvinylpyrrolidone (PVP), effectively preserved the content of FMDV VLPs during the vacuum freeze-drying process. The immunization trial in mice revealed that the levels of specific antibodies, immunoglobulin G1 (IgG1), interleukin-4 (IL-4), and neutralizing antibodies induced by freeze-dried FMDV VLPs were comparable to those induced by non-freeze-dried FMDV VLPs. The heat treatment results showed that the storage periods of freeze-dried FMDV VLPs at 4, 25, and 37 ℃ were significantly longer than those of non-freeze-dried FMDV VLPs. In conclusion, the selected lyoprotectant formulation effectively improved the stability of FMDV VLPs vaccines. This study provides valuable insights for enhancing the stability of novel subunit vaccines.
Freeze Drying/methods* ; Animals ; Foot-and-Mouth Disease Virus/immunology* ; Mice ; Vaccines, Virus-Like Particle/chemistry* ; Foot-and-Mouth Disease/immunology* ; Vacuum ; Drug Stability ; Mice, Inbred BALB C ; Viral Vaccines/immunology*

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To investigate the distribution of Traditional Chinese Medicine (TCM) syndromes in older adult patients with pneumonia who face nutritional risks, malnutrition, sarcopenia, and frailty, as well as the extent to which these syndromes affect their nutritional status.Methods:This study used a cross-sectional research design. A total of 1 263 older adult patients with pneumonia who received treatment at the Department of Traditional Chinese Medicine, The Second Hospital of Tianjin Medical University, from July 2021 to July 2024 were included in this study. These patients underwent TCM syndrome differentiation and nutritional assessments. The top 10 distribution patterns of TCM syndromes related to nutritional risk, malnutrition, sarcopenia, and frailty were identified. Logistic regression analysis was performed to analyze the effect of each syndrome pattern on nutritional risk, malnutrition, sarcopenia, and frailty. The odds ratio ( OR) value was used as the effect indicator of effect, with an OR > 1 indicating that the syndrome pattern is a risk factor for nutritional status; the larger the value, the higher the risk. Results:In older adults with pneumonia, the TCM syndrome patterns most commonly associated with nutritional risk, malnutrition, sarcopenia, and frailty were concentrated in phlegm-damp accumulation, phlegm-heat obstructing the lung, qi and blood deficiency, qi deficiency with blood stasis, qi and yin depletion, yang deficiency with water retention, spleen-stomach deficiency, lung qi depletion, and kidney deficiency with failure to grasp qi. Qi deficiency with blood stasis ( OR = 3.70) and qi and blood deficiency ( OR = 4.90) were risk factors for malnutrition. Phlegm-damp accumulation ( OR = 3.46), qi deficiency with blood stasis ( OR = 3.87), and qi and blood deficiency ( OR = 4.52) were risk factors for sarcopenia. Phlegm-damp accumulation ( OR = 2.63), phlegm-heat obstructing the lung ( OR = 3.14), qi deficiency with blood stasis ( OR = 5.78), and qi and blood deficiency ( OR = 6.33) were risk factors for frailty. Conclusions:Phlegm-dampness accumulation, phlegm-heat obstructing the lungs, deficiency of both qi and blood, and qi deficiency with blood stasis are all risk factors for nutritional risks, malnutrition, sarcopenia, and frailty in older adults. Patients with pneumonia exhibiting these patterns should pay special attention to their nutritional status, and early nutritional intervention should be implemented to prevent adverse clinical outcomes.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To investigate the distribution of Traditional Chinese Medicine (TCM) syndromes in older adult patients with pneumonia who face nutritional risks, malnutrition, sarcopenia, and frailty, as well as the extent to which these syndromes affect their nutritional status.Methods:This study used a cross-sectional research design. A total of 1 263 older adult patients with pneumonia who received treatment at the Department of Traditional Chinese Medicine, The Second Hospital of Tianjin Medical University, from July 2021 to July 2024 were included in this study. These patients underwent TCM syndrome differentiation and nutritional assessments. The top 10 distribution patterns of TCM syndromes related to nutritional risk, malnutrition, sarcopenia, and frailty were identified. Logistic regression analysis was performed to analyze the effect of each syndrome pattern on nutritional risk, malnutrition, sarcopenia, and frailty. The odds ratio ( OR) value was used as the effect indicator of effect, with an OR > 1 indicating that the syndrome pattern is a risk factor for nutritional status; the larger the value, the higher the risk. Results:In older adults with pneumonia, the TCM syndrome patterns most commonly associated with nutritional risk, malnutrition, sarcopenia, and frailty were concentrated in phlegm-damp accumulation, phlegm-heat obstructing the lung, qi and blood deficiency, qi deficiency with blood stasis, qi and yin depletion, yang deficiency with water retention, spleen-stomach deficiency, lung qi depletion, and kidney deficiency with failure to grasp qi. Qi deficiency with blood stasis ( OR = 3.70) and qi and blood deficiency ( OR = 4.90) were risk factors for malnutrition. Phlegm-damp accumulation ( OR = 3.46), qi deficiency with blood stasis ( OR = 3.87), and qi and blood deficiency ( OR = 4.52) were risk factors for sarcopenia. Phlegm-damp accumulation ( OR = 2.63), phlegm-heat obstructing the lung ( OR = 3.14), qi deficiency with blood stasis ( OR = 5.78), and qi and blood deficiency ( OR = 6.33) were risk factors for frailty. Conclusions:Phlegm-dampness accumulation, phlegm-heat obstructing the lungs, deficiency of both qi and blood, and qi deficiency with blood stasis are all risk factors for nutritional risks, malnutrition, sarcopenia, and frailty in older adults. Patients with pneumonia exhibiting these patterns should pay special attention to their nutritional status, and early nutritional intervention should be implemented to prevent adverse clinical outcomes.

Objective:To investigate the reference intervals of serum uric acid levels in normal-weight children and analyze the factors influencing these levels.Methods:In this cross-sectional study, clinical data were collected from 7 910 normal-weight children, aged 1 month to 15 years, who underwent health check-ups at the Children′s Hospital of Zhejiang University School of Medicine between August 2013 and August 2023. Data included sex, age, pubertal signs, blood pressure, and serum uric acid levels. The participants were categorized into 4 age groups: 1-<12 months, 1-<6 years, 6-<11 years, and 11-<16 years, and were further analyzed by sex. The P5 and P95 percentiles of uric acid values were defined as the lower and upper limits of the reference interval, respectively. Correlation analysis and partial correlation analysis were used to assess the relationship between uric acid and other variables such as age, body mass index Z value, and Tanner stage. Multivariate linear regression was used to compare uric acid levels across gender and age groups, respectively. Results:Among the 7 910 children, the distribution across age groups was as follows: 562 (317 boys) in 1-<12 months, 4 120 (2 366 boys) in 1-<6 years, 2 357 (1 432 boys) in 6-<11 years, and 871 (536 boys) in 11-<16 years, the uric acid levels in boys were significantly higher than those in girls ( P<0.05). Uric acid levels exhibited a positive correlation with age ( r=0.47 , 0.20, both P<0.001), and a weak positive correlation with BMI Z-scores(both r=0.11, P<0.001). Among participants aged 6-<11 years and 11-<16 years, uric acid levels in boys were positively correlated with Tanner stage ( r=0.10, 0.27, both P<0.05), but no significant correlation was observed in girls (all P>0.05). The uric acid levels were significantly higher in boys than in girls in the 1-<12 months, 1-<6 years and 11-<16 years age groups (all P<0.05), but no significant gender difference was found in the 6-<11 years groups ( P>0.05). Uric acid levels exhibited statistically significant variations among age groups ( P<0.001). The reference intervals of uric acid values were as follows in 1-<12 months age group, 157-335 μmol/L for boys and 160-315 μmol/L for girls; in 1-<6 years age group, 180-359 μmol/L for boys and 180-355 μmol/L for girls; in 6-<11 years group, 190-375 μmol/L; in 11-<16 years age group, 237-480 μmol/L for boys and 218-410 μmol/L for girls. Conclusions:Reference intervals for uric acid varying significantly across different pediatric age groups. Sex, and pubertal development status are closely related to uric acid levels.

Objective To evaluate the prognostic value of radiation-induced lymphocytopenia in the survival of patients with primary hepatocellular carcinoma receiving radiation therapy. Methods The clinical data of 98 patients with unresectable primary hepatocellular carcinoma who received radiotherapy were retrospectively analyzed. The minimum absolute lymphocyte count (min ALC) was graded in accordance with CTCAE V4.0. The optimal threshold of min ALC for prognosis was calculated by using the receiver operating characteristic curve, and the correlation of min ALC with clinical characteristics and dosimetry parameters was analyzed. The Kaplan-Meier method was employed to analyze the survival of patients with different levels of min ALC. Univariate and multivariate Cox proportional regression models were applied to analyze prognostic factors. Results The baseline and min ALC of 98 patients during radiotherapy were 1.52×10⁹/L and 0.45×10⁹/L, respectively(P<0.001). The optimal cut-off value of min ALC for the prediction of the one-year survival rate was 0.38×10⁹/L. GTV, the mean dose of the liver and spleen, the V5 and V10 of the liver and spleen, and the V15 of the spleen were correlated with min ALC, and the V5 of the liver was an independent predictor of min ALC. The overall survival of patients with high min ALC was higher than that of patients with low min ALC. Independent prognostic factors were min ALC≤0.38×10⁹/L (HR=0.515, P=0.024), min ALC≥grade 3 (HR=0.576, P=0.032), tumor thrombus in the portal/vena cava, Child-Pugh grade A, increase of ≥2 points in the Child-Pugh score after radiotherapy, and received more than two other therapies. Conclusion Min ALC≤0.38×10⁹/L and min ALC≥grade 3 have independent prognostic value in patients with unresectable hepatocellular carcinoma receiving radiotherapy.

BACKGROUND:Total knee arthroplasty is one of the effective methods to treat end-stage knee osteoarthritis.However,some patients still experience chronic post-surgical pain.It is significant to find out the influencing factors of chronic post-surgical pain.Demographic factors,social psychological factors and perioperative pain were the focus of previous studies,but muscle factors closely related to the occurrence and development of knee osteoarthritis were rarely reported. OBJECTIVE:To evaluate the value of preoperative quantitative ultrasound analysis of quadriceps femoris in predicting chronic post-surgical pain after total knee arthroplasty. METHODS:A total of 250 patients with knee osteoarthritis who underwent the first unilateral total knee arthroplasty under elective general anesthesia from January to August 2022 in the Affiliated Hospital of Xuzhou Medical University were selected.All patients were treated with the same anesthesia and operative methods.Before the surgery,clinical data were recorded,and the thickness and echo intensity of quadriceps femoris on the operated side were measured by ultrasound imaging,which could quantify the degree of quadriceps femoris atrophy.Multivariate logistic regression was used to analyze the independent factors affecting the occurrence of chronic post-surgical pain,and receiver operating characteristic curves were used to evaluate its predictive value. RESULTS AND CONCLUSION:(1)250 subjects were involved in the result analysis,and 91 of them had chronic post-surgical pain,with an incidence of 36.4%.(2)There were significant differences between the chronic pain and non-chronic pain groups in preoperative pain score during movement,preoperative Western Ontario and McMaster University Osteoarthritis Index,preoperative anxiety and depression scale score,preoperative muscle thickness and echo intensity of quadriceps femoris,and postoperative acute pain score(P<0.05).(3)Multivariate logistic regression analysis showed that preoperative thickness of quadriceps femoris was an independent protective factor for chronic post-surgical pain and preoperative pain score during movement was an independent risk factor for chronic post-surgical pain.(4)Receiver operating characteristic curves showed that the area under the curve of the preoperative thickness of quadriceps femoris was 0.625(95%CI:0.555-0.695),and the critical value was 2.78 cm,sensitivity was 0.802,specificity was 0.415.(5)It is concluded that the preoperative thickness of quadriceps femoris is an independent protective factor for chronic post-surgical pain,but its predictive efficacy is low,and its clinical application needs to be further verified or modified.