BACKGROUND:Research has shown that vanillic acid has anti-inflammatory and anti-oxidative stress effects,but it is unclear whether it has a protective effect on endplate chondrocytes.OBJECTIVE:To explore the effect and mechanism of vanillic acid on endplate chondrocytes under inflammatory microenvironment.METHODS:(1)Primary endplate chondrocytes were isolated from the intervertebral disc of SD rats and identified by toluidine blue staining and collagenⅡ immunofluorescence.(2)The CCK-8 assay was employed to detect the effects of interleukin-1β and vanillic acid on the proliferation activity of endplate chondrocytes,in order to determine the concentration of vanillic acid for subsequent cell treatment.(3)An inflammatory microenvironment was simulated by adding 10 ng/mL interleukin-1β to the culture medium,and the endplate chondrocytes were treated with low,medium,and high mass concentrations of vanillic acid.The expression levels of inflammatory markers and extracellular matrix proteins were detected by western blot assay and immunofluorescence.(4)The expression of nuclear factor κB signaling pathway-related proteins was detected by western blot assay.RESULTS AND CONCLUSION:(1)The morphology of endplate chondrocytes in adherent culture was pike or triangular in shape,positive for toluidine blue staining and immunofluorescence for collagen Ⅱ,indicating that the experimentally extracted cells were endplate chondrocytes.(2)The CCK-8 assay results showed that treatment with 2.5,5,10,and 20 μg/mL vanillic acid for 24 hours did not significantly inhibit the proliferation of endplate chondrocytes.Compared with the interleukin-1β group,the viability of endplate chondrocytes treated with 5,10,and 20 μg/mL vanillic acid for 24 hours was significantly increased(P＜0.05).Therefore,5,10,and 20 μg/mL vanillic acid was selected as the low,medium,and high dose groups for subsequent treatment of endplate chondrocytes.(3)Compared with the model group(complete medium containing 10 ng/mL interleukin-1β),the expression of NOD-like receptor thermal domain associated protein 3(NLRP3),matrix metalloproteinase 13,matrix metalloproteinase 3,and tumor necrosis factor alpha protein in the endplate chondrocytes of the low,medium,and high doses of vanillic acid groups were significantly reduced(P＜0.05).(4)Compared with the model group,the protein expression of aggrecan and collagen Ⅱ in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid significantly increased(P＜0.05).(5)Compared with the model group,the protein expression of phospho-nuclear factor κB and phospho-inhibitor of nuclear factor κB in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid was significantly reduced(P＜0.05).(6)The above results indicate that vanillic acid may alleviate the inflammatory response and extracellular matrix degradation induced by interleukin-1β in rat endplate chondrocytes by inhibiting the activation of the nuclear factor κB signaling pathway.

Bisphenol A (BPA) is an environmental chemical that is widely exposed in human daily life. It has attracted much attention because of its estrogenic effect. Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disease in women of reproductive age. Its pathogenesis involves the interaction of genetic, environmental and endocrine disorders. In recent years, more and more studies have shown that BPA plays an important role in the occurrence and development of PCOS. BPA promotes the development of PCOS by interfering with insulin sensitivity, immune response and changing ovarian structure and function. In addition, BPA exposure levels are associated with hyperandrogenism, insulin resistance, obesity, dyslipidemia, and decreased ovarian reserve in PCOS patients. This review summarizes the effects of BPA on PCOS in terms of ovarian function, glucose and lipid metabolism, and inflammatory response, so as to provide theoretical basis for clinical intervention and prevention of BPA in the development of PCOS.

Objective:To investigate the clinical efficacy and safety of needle-free and needle-based injections of recombinant human interferon (IFN) -α2a in the treatment of palmoplantar warts.Methods:Patients aged 6 to 75 years with palmoplantar warts were prospectively enrolled from the Department of Dermatology, Zhongda Hospital, Southeast University between March and September 2023, and baseline data were collected. The patients were randomly and equally divided into a needle-free injection group and a needle-based injection group by using a random number table method, and received needle-free and needle-based injections of recombinant human IFN-α2a once every 2 to 3 weeks, respectively, with a maximum of 4 treatment sessions. Efficacy was assessed based on changes in wart size and skin lines under a dermoscope. Pain degrees and adverse reactions were recorded, and patients were followed up for 6 months after the end of treatment. Chi-square test was used to compare the cure rates, recurrence rates, and incidence rates of adverse reactions between the two groups. Logistic regression analysis was employed to identify factors related to the clearance of palmoplantar warts.Results:A total of 160 patients with palmoplantar warts were included, with 80 patients in each group. In the needle-free injection group, there were 45 females (56.2%) and 35 males (43.8%) ; their ages ( M[ Q1, Q3]) were 27 (23, 40) years, and the duration of disease ( M[ Q1, Q3]) was 12 (3, 24) months; warts were located on the hands in 12 cases (15.0%), on the feet in 60 cases (75.0%), and on both sites in 8 cases (10.0%) ; warts measuring ≤ 1 cm in diameter were observed in 71 cases (88.8%), and those measuring > 1 cm were observed in 9 cases (11.3%). In the needle-based injection group, there were 37 females (46.2%) and 43 males (53.8%) ; their ages were 28 (22, 39) years, and the duration of disease was 6 (2, 12) months; warts were located on the hands in 23 cases (28.7%), on the feet in 55 cases (68.8%), and on both sites in 2 cases (2.5%) ; warts measuring ≤ 1 cm in diameter were observed in 67 cases (83.8%), and those measuring > 1 cm in diameter were observed in 13 cases (16.3%). There were no significant differences in gender distribution, age, wart diameters, prior treatment status, or number of warts between the two groups (all P > 0.05). The duration of disease was longer in the needle-free injection group than in the needle-based injection group ( P = 0.041), and the dose of interferon was lower in the needle-free injection group than in the needle-based injection group ( P < 0.001). After treatment, 44 patients (55.0%) were cured in the needle-free injection group, and 39 (48.8%) in the needle-based injection group, with no significant difference in the cure rates between the two groups ( χ2 = 0.63, P = 0.429). Among patients with multiple warts, 54.8% (23/42) were cured in the needle-free injection group, and 47.4% (18/38) in the needle-based injection group, with no significant difference in cure rates between the two groups ( χ2 = 1.28, P = 0.509). The most common adverse reaction was fever or flu-like symptoms (186 instances), which resolved spontaneously in 141 instances and resolved after treatment with oral ibuprofen in 45 instances; the incidence rate of flu-like symptoms was significantly lower in the needle-free injection group (57 instances, 21.6%) than in the needle-based injection group (129 instances, 53.3%; χ2 = 54.63, P < 0.001). The pain score was significantly lower in the needle-free injection group (3.65 ± 1.25 points) than in the needle-based injection group (5.16 ± 1.17 points, t = -7.90, P < 0.001). The logistic regression analysis showed that the duration of disease, lesion sites, patient age, and previous treatment history had no impact on the efficacy in either the needle-free injection group or the needle-based injection group (all P > 0.05) . Conclusions:The efficacy of needle-free and needle-based injections of interferon was similar in the treatment of palmoplantar warts, whereas needle-free injections resulted in less pain and a lower incidence of interferon-related adverse reactions. None of the duration of disease, lesion sites, patient age, or prior treatment status showed significant impact on the efficacy in the two groups.

Bisphenol A (BPA) is an environmental chemical that is widely exposed in human daily life. It has attracted much attention because of its estrogenic effect. Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disease in women of reproductive age. Its pathogenesis involves the interaction of genetic, environmental and endocrine disorders. In recent years, more and more studies have shown that BPA plays an important role in the occurrence and development of PCOS. BPA promotes the development of PCOS by interfering with insulin sensitivity, immune response and changing ovarian structure and function. In addition, BPA exposure levels are associated with hyperandrogenism, insulin resistance, obesity, dyslipidemia, and decreased ovarian reserve in PCOS patients. This review summarizes the effects of BPA on PCOS in terms of ovarian function, glucose and lipid metabolism, and inflammatory response, so as to provide theoretical basis for clinical intervention and prevention of BPA in the development of PCOS.

Objective:To investigate the clinical efficacy and safety of needle-free and needle-based injections of recombinant human interferon (IFN) -α2a in the treatment of palmoplantar warts.Methods:Patients aged 6 to 75 years with palmoplantar warts were prospectively enrolled from the Department of Dermatology, Zhongda Hospital, Southeast University between March and September 2023, and baseline data were collected. The patients were randomly and equally divided into a needle-free injection group and a needle-based injection group by using a random number table method, and received needle-free and needle-based injections of recombinant human IFN-α2a once every 2 to 3 weeks, respectively, with a maximum of 4 treatment sessions. Efficacy was assessed based on changes in wart size and skin lines under a dermoscope. Pain degrees and adverse reactions were recorded, and patients were followed up for 6 months after the end of treatment. Chi-square test was used to compare the cure rates, recurrence rates, and incidence rates of adverse reactions between the two groups. Logistic regression analysis was employed to identify factors related to the clearance of palmoplantar warts.Results:A total of 160 patients with palmoplantar warts were included, with 80 patients in each group. In the needle-free injection group, there were 45 females (56.2%) and 35 males (43.8%) ; their ages ( M[ Q1, Q3]) were 27 (23, 40) years, and the duration of disease ( M[ Q1, Q3]) was 12 (3, 24) months; warts were located on the hands in 12 cases (15.0%), on the feet in 60 cases (75.0%), and on both sites in 8 cases (10.0%) ; warts measuring ≤ 1 cm in diameter were observed in 71 cases (88.8%), and those measuring > 1 cm were observed in 9 cases (11.3%). In the needle-based injection group, there were 37 females (46.2%) and 43 males (53.8%) ; their ages were 28 (22, 39) years, and the duration of disease was 6 (2, 12) months; warts were located on the hands in 23 cases (28.7%), on the feet in 55 cases (68.8%), and on both sites in 2 cases (2.5%) ; warts measuring ≤ 1 cm in diameter were observed in 67 cases (83.8%), and those measuring > 1 cm in diameter were observed in 13 cases (16.3%). There were no significant differences in gender distribution, age, wart diameters, prior treatment status, or number of warts between the two groups (all P > 0.05). The duration of disease was longer in the needle-free injection group than in the needle-based injection group ( P = 0.041), and the dose of interferon was lower in the needle-free injection group than in the needle-based injection group ( P < 0.001). After treatment, 44 patients (55.0%) were cured in the needle-free injection group, and 39 (48.8%) in the needle-based injection group, with no significant difference in the cure rates between the two groups ( χ2 = 0.63, P = 0.429). Among patients with multiple warts, 54.8% (23/42) were cured in the needle-free injection group, and 47.4% (18/38) in the needle-based injection group, with no significant difference in cure rates between the two groups ( χ2 = 1.28, P = 0.509). The most common adverse reaction was fever or flu-like symptoms (186 instances), which resolved spontaneously in 141 instances and resolved after treatment with oral ibuprofen in 45 instances; the incidence rate of flu-like symptoms was significantly lower in the needle-free injection group (57 instances, 21.6%) than in the needle-based injection group (129 instances, 53.3%; χ2 = 54.63, P < 0.001). The pain score was significantly lower in the needle-free injection group (3.65 ± 1.25 points) than in the needle-based injection group (5.16 ± 1.17 points, t = -7.90, P < 0.001). The logistic regression analysis showed that the duration of disease, lesion sites, patient age, and previous treatment history had no impact on the efficacy in either the needle-free injection group or the needle-based injection group (all P > 0.05) . Conclusions:The efficacy of needle-free and needle-based injections of interferon was similar in the treatment of palmoplantar warts, whereas needle-free injections resulted in less pain and a lower incidence of interferon-related adverse reactions. None of the duration of disease, lesion sites, patient age, or prior treatment status showed significant impact on the efficacy in the two groups.

Lymphoma is a highly heterogeneous malignancy characterized by complex molecular regulatory mechanisms that result in significant differences in aggressiveness and prognosis across its subtypes.Gene copy number alteration(CNA)analysis,an emerging technology,has become a pivotal tool in the precision re-search and management of lymphoma.By detecting DNA deletions,amplifications,and chromosomal copy number changes,CNA analysis addresses the limitations of traditional cytogenetic techniques,enhances the ac-curacy of subtype classification,and aids in evaluating tumor heterogeneity and disease progression.This re-view provides a comprehensive summary of CNA detection methods and their applications in lymphoma,with a focus on recent advancements in the field.It offers a comparative analysis of CNA detection techniques and discusses their role in precision diagnosis,subtype classification,monitoring disease progression,predicting therapeutic resistance,and assessing prognosis.Additionally,the review explores the potential applications of CNA analysis in uncovering molecular regulatory mechanisms,optimizing therapeutic strategies,and impro-ving patient survival outcomes.

Objective:Using methylation characteristics of human genes to construct machine learning predictive models for screening cervical cancer and precancerous lesions.Methods:Human DNA methylation detection was performed on 224 cervical exfoliated cell specimens from the Cancer Hospital of the Chinese Academy of Medical Sciences, Tianjin Central Hospital of Gynecology Obstetrics, Xinmi Maternal and Child Health Hospital of Henan Province, West China Second Affiliated Hospital of Sichuan University, and Heping Hospital Affiliated to Changzhi Medical College collected during April 2014 and March 2015. The hypermethylated gene fragments related to cervical cancer were selected by high-density, high-association, and hypermethylated gene fragment screening and the LASSO regression algorithm. Taking cervical intraepithelial neoplasia grade 2 (CIN2) or more severe lesions as the research outcome, machine learning predictive models based on the random forest (RF), naive Bayes (NB), and support vector machine (SVM) algorithm, respectively, were constructed. A total of 144 outpatient specimens were used as the training set and 80 cervical exfoliated cell specimens from women participating in the cervical cancer screening program were used as the test set to verify the predictive models. Using histological diagnosis results as the gold standard, the detection efficacy for CIN2 or more severe lesions of the three machine learning predictive models were compared with that of the human papilloma virus (HPV) detection and cytological diagnosis.Results:In the training set of 144 cases, there were 34 cases of HPV positivity, with a positive rate of 23.61%. Cytologically, there were 37 cases diagnosed as no intraepithelial lesion or malignancy (NILM), and 107 cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) or above. Histologically, there were 28 cases without cervical intraepithelial neoplasia or benign cervical lesions, 31 cases of CIN1, 18 cases of CIN2, 31 cases of CIN3, and 36 cases of squamous cell carcinoma. Seven hypermethylated gene fragments were selected from 45 genes, and three machine learning prediction models based on the RF, NB, and SVM algorithm, respectively, were constructed. In the validation set of 80 cases, there were 28 cases of HPV positivity, with a positive rate of 35.00%. Cytologically, there were 65 cases diagnosed as NILM and 15 cases as ASC-US or above. Histologically, there were 39 cases without cervical intraepithelial neoplasia or benign cervical lesions, 10 cases of CIN1, 10 cases of CIN2, 11 cases of CIN3, and 10 cases of squamous cell carcinoma. In the validation set, the area under the curve (AUC) values of the RF model, NB model, SVM model, HPV detection, and cytological diagnosis of CIN2 or above were 0.90, 0.88, 0.82, 0.68, and 0.45, respectively. The DeLong test showed that there was no statistically significant difference in the AUC values between the RF, NB, and SVM models (all P＞0.05), and the AUC values of the RF and NB models were higher than that of HPV detection (both P＜0.01), and the AUC values of the RF, NB, and SVM models were higher than that of cytological diagnosis (all P＜0.01). Compared with the NB model, the sensitivity of the RF model was similar (80.65% vs. 77.42%), but the specificity of the NB model was much higher than that of the RF model (93.88% vs. 73.47%). Conclusion:Among the machine learning prediction models for cervical cancer and precancerous lesions constructed based on human DNA methylation, the NB model has good predictive performance for CIN2 and above lesions, and may be used for screening of cervical cancer and precancerous lesions.

BACKGROUND:Research has shown that vanillic acid has anti-inflammatory and anti-oxidative stress effects,but it is unclear whether it has a protective effect on endplate chondrocytes.OBJECTIVE:To explore the effect and mechanism of vanillic acid on endplate chondrocytes under inflammatory microenvironment.METHODS:(1)Primary endplate chondrocytes were isolated from the intervertebral disc of SD rats and identified by toluidine blue staining and collagenⅡ immunofluorescence.(2)The CCK-8 assay was employed to detect the effects of interleukin-1β and vanillic acid on the proliferation activity of endplate chondrocytes,in order to determine the concentration of vanillic acid for subsequent cell treatment.(3)An inflammatory microenvironment was simulated by adding 10 ng/mL interleukin-1β to the culture medium,and the endplate chondrocytes were treated with low,medium,and high mass concentrations of vanillic acid.The expression levels of inflammatory markers and extracellular matrix proteins were detected by western blot assay and immunofluorescence.(4)The expression of nuclear factor κB signaling pathway-related proteins was detected by western blot assay.RESULTS AND CONCLUSION:(1)The morphology of endplate chondrocytes in adherent culture was pike or triangular in shape,positive for toluidine blue staining and immunofluorescence for collagen Ⅱ,indicating that the experimentally extracted cells were endplate chondrocytes.(2)The CCK-8 assay results showed that treatment with 2.5,5,10,and 20 μg/mL vanillic acid for 24 hours did not significantly inhibit the proliferation of endplate chondrocytes.Compared with the interleukin-1β group,the viability of endplate chondrocytes treated with 5,10,and 20 μg/mL vanillic acid for 24 hours was significantly increased(P＜0.05).Therefore,5,10,and 20 μg/mL vanillic acid was selected as the low,medium,and high dose groups for subsequent treatment of endplate chondrocytes.(3)Compared with the model group(complete medium containing 10 ng/mL interleukin-1β),the expression of NOD-like receptor thermal domain associated protein 3(NLRP3),matrix metalloproteinase 13,matrix metalloproteinase 3,and tumor necrosis factor alpha protein in the endplate chondrocytes of the low,medium,and high doses of vanillic acid groups were significantly reduced(P＜0.05).(4)Compared with the model group,the protein expression of aggrecan and collagen Ⅱ in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid significantly increased(P＜0.05).(5)Compared with the model group,the protein expression of phospho-nuclear factor κB and phospho-inhibitor of nuclear factor κB in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid was significantly reduced(P＜0.05).(6)The above results indicate that vanillic acid may alleviate the inflammatory response and extracellular matrix degradation induced by interleukin-1β in rat endplate chondrocytes by inhibiting the activation of the nuclear factor κB signaling pathway.

Objective:Using methylation characteristics of human genes to construct machine learning predictive models for screening cervical cancer and precancerous lesions.Methods:Human DNA methylation detection was performed on 224 cervical exfoliated cell specimens from the Cancer Hospital of the Chinese Academy of Medical Sciences, Tianjin Central Hospital of Gynecology Obstetrics, Xinmi Maternal and Child Health Hospital of Henan Province, West China Second Affiliated Hospital of Sichuan University, and Heping Hospital Affiliated to Changzhi Medical College collected during April 2014 and March 2015. The hypermethylated gene fragments related to cervical cancer were selected by high-density, high-association, and hypermethylated gene fragment screening and the LASSO regression algorithm. Taking cervical intraepithelial neoplasia grade 2 (CIN2) or more severe lesions as the research outcome, machine learning predictive models based on the random forest (RF), naive Bayes (NB), and support vector machine (SVM) algorithm, respectively, were constructed. A total of 144 outpatient specimens were used as the training set and 80 cervical exfoliated cell specimens from women participating in the cervical cancer screening program were used as the test set to verify the predictive models. Using histological diagnosis results as the gold standard, the detection efficacy for CIN2 or more severe lesions of the three machine learning predictive models were compared with that of the human papilloma virus (HPV) detection and cytological diagnosis.Results:In the training set of 144 cases, there were 34 cases of HPV positivity, with a positive rate of 23.61%. Cytologically, there were 37 cases diagnosed as no intraepithelial lesion or malignancy (NILM), and 107 cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) or above. Histologically, there were 28 cases without cervical intraepithelial neoplasia or benign cervical lesions, 31 cases of CIN1, 18 cases of CIN2, 31 cases of CIN3, and 36 cases of squamous cell carcinoma. Seven hypermethylated gene fragments were selected from 45 genes, and three machine learning prediction models based on the RF, NB, and SVM algorithm, respectively, were constructed. In the validation set of 80 cases, there were 28 cases of HPV positivity, with a positive rate of 35.00%. Cytologically, there were 65 cases diagnosed as NILM and 15 cases as ASC-US or above. Histologically, there were 39 cases without cervical intraepithelial neoplasia or benign cervical lesions, 10 cases of CIN1, 10 cases of CIN2, 11 cases of CIN3, and 10 cases of squamous cell carcinoma. In the validation set, the area under the curve (AUC) values of the RF model, NB model, SVM model, HPV detection, and cytological diagnosis of CIN2 or above were 0.90, 0.88, 0.82, 0.68, and 0.45, respectively. The DeLong test showed that there was no statistically significant difference in the AUC values between the RF, NB, and SVM models (all P＞0.05), and the AUC values of the RF and NB models were higher than that of HPV detection (both P＜0.01), and the AUC values of the RF, NB, and SVM models were higher than that of cytological diagnosis (all P＜0.01). Compared with the NB model, the sensitivity of the RF model was similar (80.65% vs. 77.42%), but the specificity of the NB model was much higher than that of the RF model (93.88% vs. 73.47%). Conclusion:Among the machine learning prediction models for cervical cancer and precancerous lesions constructed based on human DNA methylation, the NB model has good predictive performance for CIN2 and above lesions, and may be used for screening of cervical cancer and precancerous lesions.

The etiology of rhabdomyolysis in adults is multifaceted,with one cause being physical exertion,termed exertional rhabdomyolysis(ERM).Characterized primarily by the destruction of muscle cells,ERM results in the release of intracellular contents into the bloodstream,leading to a spectrum of symptoms,including myalgia,dark urine,weakness,and marked elevations in serum creatine kinase(CK)and myoglobin levels.Some patients experience recurrent symptoms,persistently high serum CK levels(exceeding 50 times the normal upper limit),or unexplained severe manifestations.Despite this,the underlying pathogenesis remains elusive in numerous cases.Recent studies have implicated mutations in the RYR1 gene as a potential cause of exercise-induced ERM.This report describes a patient presenting with ERM and a heterozygous RYR1 gene missense mutation.Following treatment with fluid resuscitation,metabolic optimization,and antioxidant therapy,the patient exhibited clinical and biochemical improvement.