1.Xianglian Huazhuo Prescription Regulates GP73/PERK/ATF4 Signaling Pathway to Influence Endoplasmic Reticulum Stress and Ameliorate Chronic Atrophic Gastritis
Pengli DU ; Yuxi GUO ; Yican WANG ; Ziqi JIN ; Xin KANG ; Xuemei JIA ; Weichao XU ; Yanru CAI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):19-28
ObjectiveTo explore the mechanism by which Xianglian Huazhuo prescription ameliorates chronic atrophic gastritis (CAG) through regulating the Golgi protein 73 (GP73)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway and modulating endoplasmic reticulum stress (ERS). MethodA mouse model of CAG was induced by multiple factors, including ranitidine, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and irregular feeding. The CAG mice were randomized into five groups: model, Morodan (2.0 g·kg-1), and high-dose, medium-dose, and low-dose (7.6, 3.8, 1.9 g·kg-1, respectively) Xianglian Huazhuo prescription, with 10 mice in each group. At the same time, 10 mice in normal group were set up. The mice in the Morodan group and the high-dose, medium-dose, and low-dose groups of Xianglian Huazhuo prescription were administrated with corresponding agents by gavage, and those in the normal group and the model group were administrated with an equal volume of normal saline. All the mice were intervened once a day for 60 consecutive days. After the last administration, the overall morphological changes of the gastric tissue were observed. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were used to evaluate the pathological morphology and the endoplasmic reticulum ultrastructure in the gastric tissue. The serum levels of pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), gastrin-17 (G-17), and GP73 were determined by enzyme-linked immunosorbent assay (ELISA). The pepsinogen ratio (PGR, PGⅠ/PGⅡ) was calculated. The protein levels of GP73, PERK, phosphorylated (p)-PERK, glucose-regulated protein 78 (GRP78), ATF4, CCAAT enhancer-binding protein homologous protein (CHOP), cysteinyl aspartate-specific protease-12 (Caspase-12), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were assessed by Western blot. The expression of GRP78 was detected by immunofluorescence (IF) assay, and the location of Bcl-2 and Bax by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed pale gastric mucosa with flattened folds and reduced and loosely arranged gastric mucosal glands, declined serum levels of PGI, PGR, G-17, and GP73 (P<0.01). downregulated protein levels of GP73, p-PERK, ATF4, GRP78, CHOP, Caspase-12, and Bax in the gastric tissue, and upregulated protein level of Bcl-2 (P<0.01). Compared with the model group, the Morodan group and each Xianglian Huazhuo prescription group exhibited red gastric mucosa with increased folds, alleviated pathological damage, swelling endoplasmic reticulum, elevated serum levels of PGI, G-17, and GP73 (P<0.05, P<0.01), and upregulated protein levels of Caspase-12 and Bax and downregulated protein level of Bcl-2 in the gastric tissue (P<0.05, P<0.01). The Morodan group and the high-dose and medium-dose Xianglian Huazhuo prescription groups exhibited increased serum level of PGR (P<0.05, P<0.01) and upregulated protein levels of GP73, p-PERK, ATF4, GRP78, and CHOP in the gastric tissue (P<0.05, P<0.01). ConclusionXianglian Huazhuo prescription can activate the GP73/PERK/ATF4 signaling pathway and induce ERS-mediated apoptosis to alleviate the pathological damage of the gastric mucosa, thereby demonstrating a protective effect against CAG in mice.
2.Xianglian Huazhuo Prescription Regulates GP73/PERK/ATF4 Signaling Pathway to Influence Endoplasmic Reticulum Stress and Ameliorate Chronic Atrophic Gastritis
Pengli DU ; Yuxi GUO ; Yican WANG ; Ziqi JIN ; Xin KANG ; Xuemei JIA ; Weichao XU ; Yanru CAI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):19-28
ObjectiveTo explore the mechanism by which Xianglian Huazhuo prescription ameliorates chronic atrophic gastritis (CAG) through regulating the Golgi protein 73 (GP73)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway and modulating endoplasmic reticulum stress (ERS). MethodA mouse model of CAG was induced by multiple factors, including ranitidine, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and irregular feeding. The CAG mice were randomized into five groups: model, Morodan (2.0 g·kg-1), and high-dose, medium-dose, and low-dose (7.6, 3.8, 1.9 g·kg-1, respectively) Xianglian Huazhuo prescription, with 10 mice in each group. At the same time, 10 mice in normal group were set up. The mice in the Morodan group and the high-dose, medium-dose, and low-dose groups of Xianglian Huazhuo prescription were administrated with corresponding agents by gavage, and those in the normal group and the model group were administrated with an equal volume of normal saline. All the mice were intervened once a day for 60 consecutive days. After the last administration, the overall morphological changes of the gastric tissue were observed. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were used to evaluate the pathological morphology and the endoplasmic reticulum ultrastructure in the gastric tissue. The serum levels of pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), gastrin-17 (G-17), and GP73 were determined by enzyme-linked immunosorbent assay (ELISA). The pepsinogen ratio (PGR, PGⅠ/PGⅡ) was calculated. The protein levels of GP73, PERK, phosphorylated (p)-PERK, glucose-regulated protein 78 (GRP78), ATF4, CCAAT enhancer-binding protein homologous protein (CHOP), cysteinyl aspartate-specific protease-12 (Caspase-12), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were assessed by Western blot. The expression of GRP78 was detected by immunofluorescence (IF) assay, and the location of Bcl-2 and Bax by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed pale gastric mucosa with flattened folds and reduced and loosely arranged gastric mucosal glands, declined serum levels of PGI, PGR, G-17, and GP73 (P<0.01). downregulated protein levels of GP73, p-PERK, ATF4, GRP78, CHOP, Caspase-12, and Bax in the gastric tissue, and upregulated protein level of Bcl-2 (P<0.01). Compared with the model group, the Morodan group and each Xianglian Huazhuo prescription group exhibited red gastric mucosa with increased folds, alleviated pathological damage, swelling endoplasmic reticulum, elevated serum levels of PGI, G-17, and GP73 (P<0.05, P<0.01), and upregulated protein levels of Caspase-12 and Bax and downregulated protein level of Bcl-2 in the gastric tissue (P<0.05, P<0.01). The Morodan group and the high-dose and medium-dose Xianglian Huazhuo prescription groups exhibited increased serum level of PGR (P<0.05, P<0.01) and upregulated protein levels of GP73, p-PERK, ATF4, GRP78, and CHOP in the gastric tissue (P<0.05, P<0.01). ConclusionXianglian Huazhuo prescription can activate the GP73/PERK/ATF4 signaling pathway and induce ERS-mediated apoptosis to alleviate the pathological damage of the gastric mucosa, thereby demonstrating a protective effect against CAG in mice.
3.Effect of hand transmitted vibration on fingertip thermotactile perception threshold in grinding workers
Danying ZHANG ; Maosheng YAN ; Hansheng LIN ; Sizhi CHEN ; Xuemei SONG ; Bin XIAO ; Hua YAN ; Guoyong XU ; Zhipeng HE
China Occupational Medicine 2025;52(5):540-544
Objective To analyze the effect of hand transmitted vibration on fingertip thermotactile perception threshold (TPT) among grinding workers in a sports equipment manufacturing enterprise. Methods A total of 151 male grinding workers from a sports equipment manufacturing enterprise in Guangdong Province were enrolled in the vibration exposure group, and 51 male workers without hand-transmitted vibration exposure were enrolled in the control group, using the judgment sampling method. Basic health conditions of the workers were surveyed in both groups. The TPTs of the distal phalanges of the index and little fingers on both hands were tested using an HVLab thermal perception tester. Results The detection rates of finger numbness and tingling among workers in the vibration exposure group were higher than those in the control group (92.1% vs 7.8% and 59.6% vs 0.0%, respectively, both P<0.01). The detection rates of numbness or tingling of different fingers in the vibration exposure group descended in the following order: index finger, middle finger, ring finger, thumb and little finger. The hot threshold of the index finger and little finger increased (all P<0.01), while the cold threshold decreased (all P<0.01) in the vibration exposure group, compared with the control group. The results of generalized linear regression analysis showed that with the increase of the duration of hand-transmitted vibration, the hot threshold of the index finger and the little finger of both hands increased (all P<0.01), and the cold threshold decreased (all P<0.01). The hot thresholds of workers with numbness of both the index fingers and left little finger were higher than those of workers without numbness of the same finger (all P<0.05). The hot threshold of workers with tingling of the left index finger was higher than those without tingling (P<0.05). The cold thresholds of workers with tingling of the both index fingers and left little finger were lower than those without tingling of the same finger (all P<0.05). The hot threshold of the right little finger increased with age (P<0.01), while the cold thresholds of both little fingers decreased with age (all P<0.01). Conclusion Hand-transmitted vibration exposure increases fingertip hot threshold and decreases fingertip cold threshold of workers exposed to hand-transmitted vibration. Years of service in hand-transmitted vibration work, finger numbness or tingling, and age were influencing factors of TPT. Fingertip TPT examination can be used to assist in the early detection of vibration-induced nerve injury in workers exposed to hand-transmitted vibration.
4.Effects of Buyang Huanwu Decoction Regulating Cav-1/Notch1/Hes1 Signaling Pathway on Nerve Regeneration after Cerebral Ischemia in Mice
Fanzuo ZENG ; Xuemei CHEN ; Yin OUYANG ; Bowei CHEN ; Jian YI ; Yaqian XU ; Wanling NING ; Baiyan LIU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(5):114-120
Objective To investigate the effects of Buyang Huanwu Decoction on nerve regeneration after cerebral ischemia in mice based on Cav-1/Notch1/Hes1 signaling pathway.Methods Wild(WT)and Cav-1-/-(KO)male mice were randomly divided into sham-operation group,model group and Buyang Huanwu Decoction group,with 10 mice in each group.The middle cerebral artery occlusion method was used to construct the mouse cerebral ischemia model.After modeling,5-ethynyl-2'-deoxyuridine(EdU)was injected intraperitoneally every 7 days for 3 times(with an interval of 8 hours).Buyang Huanwu Decoction group was given 18.5 g/kg Buyang Huanwu Decoction by gavage daily,while the sham-operation group and model group were given distilled water of equal volume by gavage for 21 consecutive days.The neurological function of mice was evaluated using modified neurological severity score,brain tissue morphology was observed through HE staining,nerve regeneration in the ischemic side injury area was detected using dual immunofluorescence staining,Western blot was used to detect the expressions of Notch1 and Hes1 protein in ischemic cortical area.Results Compared with the same genotype sham-operation group,the neurological function score of the mice in the WT and KO model groups significantly increased(P<0.01),the arrangement of neurons in the ischemic cortical area was disordered,with nucleoli shrinking,marginalization,and even rupture,widened intercellular spaces,intracellular edema and vacuolar changes,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area significantly increased(P<0.01).Compared with the same genotype model group,the neurological function score of the WT and KO Buyang Huanwu Decoction group significantly decreased(P<0.01),the neurons in the ischemic cortical area were arranged neatly and structurally intact,with reduced intercellular space and clear nucleoli,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area was significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area were significantly decreased(P<0.01).Compared with the corresponding WT group,the neurological function scores of mice in the KO model group and KO Buyang Huanwu Decoction group significantly increased(P<0.01),the neurons in the ischemic cortical area had more severe nucleolar condensation,marginalization and rupture,with more vacuolar changes and ischemic injury,the co-localization of EdU/Nestin and EdU/NeuN in the ischemic side injury area was significantly decreased(P<0.01),and the expression of Notch1 and Hes1 proteins in ischemic cortical area significantly increased(P<0.01).Conclusion Buyang Huanwu Decoction can promote nerve regeneration after cerebral ischemia,which may be related to the regulation of Cav-1 thereby inhibition Notch1//Hes1 signaling pathway activity.
5.Study on relationship between qSOFA score, serum procalcitonin, lactic acid and hypersensitive C-reactive protein levels and with the prognosis of SAP patients
Jun LIU ; Yao CHEN ; Xuemei XU ; Shijie YU
Clinical Medicine of China 2025;41(6):452-458
Objective:To investigate the relationship between the quick sequential organ failure assessment (qSOFA) score, procalcitonin (PCT), blood lactate, hypersensitive C-reactive protein (hs-CRP) levels, and the prognosis of patients with severe acute pancreatitis (SAP).Methods:This retrospective analysis included 225 pancreatitis cases admitted to the Department of Gastroenterology at Ganzi Tibetan Autonomous Prefecture People's Hospital between February 2020 and February 2025. Patients were categorized into three groups based on severity: SAP group ( n=125), moderately severe acute pancreatitis (MSAP) group ( n=50), and mild acute pancreatitis (MAP) group ( n=50). General patient data, qSOFA scores, PCT, lactate, and hs-CRP levels were compared among the groups. Within the SAP group, patients were further divided into a favorable prognosis group ( n=101) and a poor prognosis group ( n=24) based on 28-day survival. The relationship between qSOFA score, PCT, lactate, hs-CRP, and SAP prognosis was analyzed. Normally distributed continuous data were expressed as Mean±SD. Independent samples t-test was used on comparison between two groups, while one-way ANOVA was used on comparison among multiple groups. LSD test was used on post-hoc pairwise comparison. Categorical data were expressed as n(%) and compared by χ2 test. Spearman correlation analysis assessed the correlation between qSOFA score, PCT, lactate, hs-CRP levels, and acute pancreatitis (AP) severity. Multivariable logistic regression modeling was used for joint prediction, incorporating qSOFA score, serum PCT, lactate, and hs-CRP levels to calculate combined predictive efficacy. The predictive performance of each indicator for prognosis was evaluated using receiver operating characteristic (ROC) curves. The areas under the ROC curves (AUC) were compared using DeLong's test. Results:Significant differences were observed among the MAP, MSAP, and SAP groups for qSOFA score [(0.63±0.29), (1.32±0.37), (1.70±0.33) points], serum PCT [(4.06±0.74), (5.35±0.89), (6.12±0.98) μg/L], lactate [(1.74±0.32), (2.77±0.70), (4.29±1.06) mmol/L], and hs-CRP levels [(15.38±3.75), (27.64±5.09), (35.26±6.42) mg/L] ( F values=187.51, 91.83, 169.18, 223.92, respectively, all P<0.001). The SAP group had significantly higher levels of qSOFA score, serum PCT, lactate, and hs-CRP compared to both the MAP and MSAP groups (all P<0.05), and the MSAP group levels were significantly higher than the MAP group (all P<0.05). The poor prognosis group had significantly higher levels of qSOFA score [(1.92±0.19) points], PCT [(6.65±0.47) μg/L], lactate [(5.14±0.62) mmol/L], and hs-CRP [(40.65±4.73) mg/L] compared to the favorable prognosis group [(1.65±0.25) points, (5.99±0.84) μg/L, (4.09±0.94) mmol/L, (34.16±6.09) mg/L] ( t values=4.96, 3.71, 5.20, 4.88, respectively, all P<0.001). Multivariate logistic regression analysis identified qSOFA score ( OR=14.658, 95% CI: 2.612-82.253), PCT ( OR=2.809, 95% CI: 1.288-6.129), lactate ( OR=3.658, 95% CI: 1.635-8.187), and hs-CRP ( OR=1.168, 95% CI: 1.055-1.293) as independent influencing factors for SAP patient prognosis ( P=0.002, 0.010, 0.002, 0.003, respectively). ROC curve analysis showed that the AUCs for qSOFA score, PCT, lactate, and hs-CRP in predicting poor prognosis in SAP patients were 0.754, 0.856, 0.766, and 0.809, with sensitivities of 87.50%, 83.33%, 83.33%, 85.50%, and specificities of 60.40%, 77.20%, 64.40%, 75.20%, respectively. The combined prediction model yielded an AUC of 0.934, with a sensitivity of 95.80% and specificity of 72.30%. Conclusion:The qSOFA score, PCT, blood lactate, and hs-CRP levels are associated with the severity of AP and possess reference value for predicting the prognosis of SAP patients.
6.Construction and validation of a risk prediction model for delayed medical treatment in patients with acute myocardial infarction
Yuanfeng XU ; Chenglin ZHANG ; Xuemei LI ; Xiaoyan LI ; Wu CHEN
China Modern Doctor 2025;63(10):16-19,33
Objective To construct a risk prediction model for delayed medical treatment in patients with acute myocardial infarction(AMI),and to evaluate the predictive performance of the model.Methods Convenience sampling method was used to select 219 patients with AMI who were hospitalized in Yancheng Third People's Hospital from March 2023 to May 2024 as investigation objects.The patients with AMI were divided into delayed group(n=106)and undelayed group(n=1 13)with the 6-hour interval.Logistic regression analysis was used to establish a risk prediction model for AMI patients with delayed medical treatment.Hosmer-Lemeshow test and receiver operating characteristic curve were used to evaluate the goodness of fit and prediction ability of the model.Results Binary Logistic regression analysis showed that age,unknown heart disease at the time of onset,first chest pain and low score of brief health literacy screen were all risk factors for delayed medical treatment in AMI patients(P<0.05).The model predicted that the area under the curve of AMI patients with delayed hospitalization was 0.771,the Youden index was 0.562,the optimal cutoff value was 0.514,and the sensitivity and specificity were 77.3%and 86.5%,respectively.Conclusion The constructed risk prediction model can effectively predict and screen the high-risk groups of AMI patients with delayed medical treatment,reduce the risk of AMI patients with delayed medical treatment,and provide a scientific basis for taking reasonable intervention measures to shorten the time of medical treatment for AMI patients.
7.Inhibitory effect of berberine on formation of biofilms of clinical methicillin-resistant Staphylococcus aureus isolates
Mingming JIANG ; Fangfang ZHOU ; Xuemei GU ; Yanan LI ; Minyi XU ; Lei WANG
Chinese Journal of Nosocomiology 2025;35(21):3243-3248
OBJECTIVE To explore the effect and potential mechanisms of berberine on formation of biofilms of clinical methicillin-resistant Staphylococcus aureus(MRSA)isolates.METHODS Totally 95 clinical MRSA iso-lates were collected from Shanghai Eighth People's Hospital from Jan.2023 to Dec.2023.The 14 biofilm forma-tion-related genes in the strains were detected by polymerase chain reaction(PCR)and multiplex PCR,the mini-mum inhibitory concentration(MIC)of berberine was determined by microbroth dilution method,the effect of berberine on resistance of biofilm formation was evaluated by crustal violet staining,fluorescence microscope,Congo red agar plate and extracelluar DNA(eDNA).The transcription levels of 9 biofilm formation-related genes were detected by real-time fluorescent quantitative reverse transcription PCR.RESULTS All of the 95 strains of MRSA carried eno,clfA,clfB and icaA genes,the most widespread gene profile was bbp-eno-ebpS-fnbA-fib-clfA-clfB-icaA-sasG,and 29 strains had the phenotypes with strong capability of biofilm formation.The MIC score of berberine ranged between 64 and 1 024 μg/ml.Berberine with the concentration of 1/2 MIC could inhibit the biofilm formation of MRSA(P<0.001),and the inhibiting rate of biofilm formation of the MIC ≥512 μg/ml group was higher than that of the MIC≤128 μg/ml group and the MIC 256 μg/ml group(all P<0.05).The re-sult under the fluorescence microscope showed that the fluorescence intensity of biofilms decreased with the rise of berberine concentration.Berberine could reduce the formation of amyloid fibrils and the release of eDNA,down-regulating the transcription levels of ica A,sasG,ebpS,fib,eno,clfA,clfB,bbp and fnbA genes(P<0.05).CONCLUSION Berberine may inhibit the biofilm formation of MRSA by downregulating expression levels of related genes,interfering the formation of amyloid fibrils and blocking the release of eDNA,which may provide experimental bases for development of drugs resisting to MRSA biofilms.
8.Comparison of efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children: a multicenter, randomized, controlled clinical trial
Xing XIAO ; Shan WANG ; Huan YANG ; Hong SHU ; Yanping GUO ; Jinping CHEN ; Yao LU ; Qinfeng LI ; Yuan LIANG ; Mutong ZHAO ; Xiaoyan LUO ; Limin MIAO ; Rui XU ; Xuemei LI ; Sha LAI ; Jianhong LI ; Zhen LUO ; Lu YU ; Lu XING ; Meitan WANG ; Xiaoli LI ; Haitao XU ; Ping LI ; Hua WANG ; Lin MA
Chinese Journal of Dermatology 2025;58(5):425-430
Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.
9.Role of cancer-associated fibroblasts autophagy in papillary thyroid cancer
Xuemei ZHANG ; Danyang SUN ; Ning LI ; Qicheng ZHANG ; Ke XU ; Wei ZHENG ; Qiang JIA ; Jian TAN ; Zhaowei MENG
Chinese Journal of Endocrinology and Metabolism 2025;41(2):135-144
Objective:To investigate the inpact of thyroid cancer-derived cancer-associated fibroblasts(CAF) autophagy on papillary thyroid cancer(PTC).Methods:CAF and normal fibroblasts were isolated from cancerous and adjacent normal thyroid tissues from four PTC patients. Expressions of fibroblast activation protein(FAP) and α-smooth muscle actin in cells were assessed. Conditioned medium of CAF and normal fibroblasts were prepared and used to culture PTC cells. The effects of CAF and normal fibroblasts on survival, proliferation, migration, invasion and iodine uptake of PTC cells were evaluated through cell proliferation assay, cell scratch assay, cell invasion assay, and cell iodine uptake assay. The autophagy level of CAF was also evaluated. Autophagy inhibition and activation were used to regulate the autophagy of CAF, and then their effects on PTC cell proliferation, migration and invasion were further evaluated. The in vivo effect of CAF autophagy on PTC xenograft tumor growth was evaluated.Results:CAF exhibited higher FAP expression and basal autophagy levels. PTC cells co-cultured with CAF-conditioned media showed enhanced proliferation, migration, invasion, and reduced iodine uptake. Autophagy inhibition reduced these effects, while autophagy activation further promoted them. In vivo, inhibiting CAF autophagy suppressed tumor growth.Conclusions:CAF promotes PTC cell malignancy through autophagy activation, enhancing proliferation, migration, and invasion while reducing iodine uptake.
10.Clinical characteristics of juvenile dermatomyositis in anti-nuclear matrix protein 2 antibody-positive patients and risk factors for severity: a national multicenter retrospective study
Huiyuan YANG ; Wanzhen GUAN ; Ling2 YANG ; Haimei LIU ; Xiaoqing3 LI ; Haiguo YU ; Meiping LU ; Jun YANG ; Xiaohui LIU ; Hongxia ZHANG ; Wei ZHANG ; Jihong XIAO ; Xiaozhong LI ; Guomin LI ; Hong CHANG ; Sheng HAO ; Yue DU ; Daliang XU ; Ling WU ; Wenjie ZHENG ; Li LIU ; Xinhui JIANG ; Shaohui ZHU ; Dongmei ZHAO ; Xuemei TANG ; Li SUN
Chinese Journal of Pediatrics 2025;63(12):1299-1305
Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

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