Objective:To analyze the clinical characteristics, RAN-binding protein 2 ( RANBP2) gene variations, and prognosis in Chinese acute necrotizing encephalopathy (ANE) patients. Methods:A retrospective analysis of ANE cases registered in the Peking Union Medical College Hospital Encephalitis Registry System from 2022 to 2024, involving patients from Peking Union Medical College Hospital and other hospitals, was conducted. A descriptive study was performed on the clinical characteristics, treatments and prognosis, cerebrospinal fluid examination results, and imaging findings of these patients based on adjusted ANE diagnostic criteria. Whole-exome sequencing technology was used to detect gene mutations in these patients.Results:A total of 18 ANE cases were included, ranged in age from 2 to 72 [20(5, 43)] years. The male-to-female ratio was 4∶5. All patients were found with precipitating infections including COVID-19, influenza A virus and Mycoplasma pneumoniae infections. All patients presented with fever, with varying degrees of consciousness disturbance observed in 16 cases, and seizures in 10 cases. All patients underwent lumbar puncture, with normal or mildly elevated white cell counts [3(2, 13)×10 6/L] and mildly to moderately elevated protein levels [1.90(0.92, 4.65) g/L]. A total of 6 patients were found with extremely elevated interleukin-6 level [950(164, 2 000) pg/ml] in cerebrospinal fluid. Bilateral symmetric thalamic lesions were typical imaging features of ANE, while involvement of other areas such as cortical and subcortical white matter, brainstem, and cerebellum was also observed. A total of 14 patients performed genetic tests while 4 patients were identified with RANBP2 gene mutations (c.1754C>T in 3 cases, c.1966A>G in 1 case). All patients received immunotherapy, and 7 patients died at discharge while other patients presented with neurological sequelae of varying degrees. Conclusions:ANE is a rare and severe parainfectious encephalopathy that can occur in both children and adults. Clinically, it is characterized by rapidly progressing encephalopathy following systematic infection, with bilateral symmetric thalamic lesions. The detection of RANBP2 gene mutations could help make the diagnosis.

Objective:To analyze sentinel symptoms in gastric cancer chemotherapy patients based on symptom cluster theory and provide a basis for effective symptom assessment and management.Methods:A convenience sampling method was used to select gastric cancer patients undergoing chemotherapy at the First Affiliated Hospital of Zhengzhou University from June 2022 to May 2023. Patients were surveyed using a basic demographic questionnaire and the M.D. Anderson Symptom Inventory (MDASI). The Apriori algorithm was applied to identify sentinel symptoms within symptom clusters during chemotherapy.Results:A total of 195 questionnaires were distributed, and 187 valid responses were collected, yielding a response rate of 95.90% (187/195). A total of four symptom clusters were identified: physical symptom cluster (fatigue-pain-restless sleep-drowsiness-weight loss), gastrointestinal symptom cluster (nausea-appetite loss-dry mouth-vomiting), emotional symptom cluster (sadness-distress), and gastric cancer-specific symptom cluster (feeling full-changed appetite-diarrhea-constipation). Fatigue, nausea, sadness, and feeling full were identified as sentinel symptoms for the physical, gastrointestinal, emotional, and gastric cancer-specific symptom clusters, respectively.Conclusions:Gastric cancer chemotherapy patients experience various symptom clusters, with fatigue, nausea, sadness, and feeling full being potential sentinel symptoms within their respective clusters.

Objective:To analyze the clinical characteristics, RAN-binding protein 2 ( RANBP2) gene variations, and prognosis in Chinese acute necrotizing encephalopathy (ANE) patients. Methods:A retrospective analysis of ANE cases registered in the Peking Union Medical College Hospital Encephalitis Registry System from 2022 to 2024, involving patients from Peking Union Medical College Hospital and other hospitals, was conducted. A descriptive study was performed on the clinical characteristics, treatments and prognosis, cerebrospinal fluid examination results, and imaging findings of these patients based on adjusted ANE diagnostic criteria. Whole-exome sequencing technology was used to detect gene mutations in these patients.Results:A total of 18 ANE cases were included, ranged in age from 2 to 72 [20(5, 43)] years. The male-to-female ratio was 4∶5. All patients were found with precipitating infections including COVID-19, influenza A virus and Mycoplasma pneumoniae infections. All patients presented with fever, with varying degrees of consciousness disturbance observed in 16 cases, and seizures in 10 cases. All patients underwent lumbar puncture, with normal or mildly elevated white cell counts [3(2, 13)×10 6/L] and mildly to moderately elevated protein levels [1.90(0.92, 4.65) g/L]. A total of 6 patients were found with extremely elevated interleukin-6 level [950(164, 2 000) pg/ml] in cerebrospinal fluid. Bilateral symmetric thalamic lesions were typical imaging features of ANE, while involvement of other areas such as cortical and subcortical white matter, brainstem, and cerebellum was also observed. A total of 14 patients performed genetic tests while 4 patients were identified with RANBP2 gene mutations (c.1754C>T in 3 cases, c.1966A>G in 1 case). All patients received immunotherapy, and 7 patients died at discharge while other patients presented with neurological sequelae of varying degrees. Conclusions:ANE is a rare and severe parainfectious encephalopathy that can occur in both children and adults. Clinically, it is characterized by rapidly progressing encephalopathy following systematic infection, with bilateral symmetric thalamic lesions. The detection of RANBP2 gene mutations could help make the diagnosis.

Objective:To analyze sentinel symptoms in gastric cancer chemotherapy patients based on symptom cluster theory and provide a basis for effective symptom assessment and management.Methods:A convenience sampling method was used to select gastric cancer patients undergoing chemotherapy at the First Affiliated Hospital of Zhengzhou University from June 2022 to May 2023. Patients were surveyed using a basic demographic questionnaire and the M.D. Anderson Symptom Inventory (MDASI). The Apriori algorithm was applied to identify sentinel symptoms within symptom clusters during chemotherapy.Results:A total of 195 questionnaires were distributed, and 187 valid responses were collected, yielding a response rate of 95.90% (187/195). A total of four symptom clusters were identified: physical symptom cluster (fatigue-pain-restless sleep-drowsiness-weight loss), gastrointestinal symptom cluster (nausea-appetite loss-dry mouth-vomiting), emotional symptom cluster (sadness-distress), and gastric cancer-specific symptom cluster (feeling full-changed appetite-diarrhea-constipation). Fatigue, nausea, sadness, and feeling full were identified as sentinel symptoms for the physical, gastrointestinal, emotional, and gastric cancer-specific symptom clusters, respectively.Conclusions:Gastric cancer chemotherapy patients experience various symptom clusters, with fatigue, nausea, sadness, and feeling full being potential sentinel symptoms within their respective clusters.

Objective To explore whether the effect of urine-derived stem cells(USCs)on chondro-cytes in osteoarthritis(OA)is related to the PI3K/AKT pathway.Methods Human urine was collected aseptically,and primary USCs were isolated and cultured through specific steps.Meanwhile,chondro-cytes were extracted from the knee joints of Sprague-Dawley rats to establish the OA model.USCs were co-cultured with OA chondrocytes by using Transwell co-culture system,and the transcriptome changes of chondrocytes before and after co-culture were analyzed by using the high-throughput RNA sequencing.Moreover,the phosphorylation levels of key proteins of the PI3K/AKT/mTOR pathway were detected using protein immunoblotting,and the PI3K agonist 740 Y-P was employed to further vali-date the relationship between the protective effect of USCs on OA chondrocytes,as well as its possi-ble relationship to the PI3K/AKT pathway and the possible mechanism.Results Transcriptomic analysis showed that the protective effect of USCs on OA chondrocytes might be related to the'PI3K-Akt sig-naling pathway'.Protein level analysis confirmed that USCs significantly inhibited the PI3K/AKT/mTOR pathway in OA chondrocytes.Moreover,protein immunoblotting and immunofluorescence showed that USCs improved the expression of OA-related proteins and autophagy-related proteins in OA chondro-cytes.What's more,the inhibitory effect of USCs on the PI3K/AKT/mTOR pathway was partially re-versed by using the PI3K agonist 740 Y-P,while the protective and autophagy-promoting effects of USCs on OA chondrocytes were down-regulated.Conclusion This study reveals the potential protective effect of USCs on OA chondrocytes through inhibition of the PI3K/AKT/mTOR signalling pathway and its close correlation with improved autophagy.Therefore,it provides a research basis and theoretical support for the future application of USCs in the treatment of OA.

Objective To explore whether the effect of urine-derived stem cells(USCs)on chondro-cytes in osteoarthritis(OA)is related to the PI3K/AKT pathway.Methods Human urine was collected aseptically,and primary USCs were isolated and cultured through specific steps.Meanwhile,chondro-cytes were extracted from the knee joints of Sprague-Dawley rats to establish the OA model.USCs were co-cultured with OA chondrocytes by using Transwell co-culture system,and the transcriptome changes of chondrocytes before and after co-culture were analyzed by using the high-throughput RNA sequencing.Moreover,the phosphorylation levels of key proteins of the PI3K/AKT/mTOR pathway were detected using protein immunoblotting,and the PI3K agonist 740 Y-P was employed to further vali-date the relationship between the protective effect of USCs on OA chondrocytes,as well as its possi-ble relationship to the PI3K/AKT pathway and the possible mechanism.Results Transcriptomic analysis showed that the protective effect of USCs on OA chondrocytes might be related to the'PI3K-Akt sig-naling pathway'.Protein level analysis confirmed that USCs significantly inhibited the PI3K/AKT/mTOR pathway in OA chondrocytes.Moreover,protein immunoblotting and immunofluorescence showed that USCs improved the expression of OA-related proteins and autophagy-related proteins in OA chondro-cytes.What's more,the inhibitory effect of USCs on the PI3K/AKT/mTOR pathway was partially re-versed by using the PI3K agonist 740 Y-P,while the protective and autophagy-promoting effects of USCs on OA chondrocytes were down-regulated.Conclusion This study reveals the potential protective effect of USCs on OA chondrocytes through inhibition of the PI3K/AKT/mTOR signalling pathway and its close correlation with improved autophagy.Therefore,it provides a research basis and theoretical support for the future application of USCs in the treatment of OA.

Objective:To observe the efficacy and safety of recombinant human thrombopoietin (rhTPO) in the treatment of radiation induced thrombocytopenia (RIT) .Methods:From January 2019 to March 2021, 204 cases (including 101 cases of radiotherapy alone and 103 cases of concurrent chemoradiotherapy) were collected retrospectively after radiotherapy and with decreased in blood platelet count <75×10 9/L in Jilin Cancer Hospital. These patients received rhTPO 15 000 U, once a day, subcutaneous, for at least 4 consecutive days, or met the withdrawal criteria blood platelet count ≥100×10 9/L, or the absolute value of blood platelet increase ≥50×10 9/L. The characteristics of blood platelet decline, treatment efficacy, and safety were analyzed. Results:The numbers of radiotherapy treatments with platelets lower than 75×10 9/L in the radiotherapy alone group and the concurrent chemoradiotherapy group were 19 (13, 22) and 13 (10, 17) times, respectively, indicating that patients in the concurrent chemoradiotherapy group experienced platelet decline earlier ( Z=-5.27, P<0.001), the lowest values of platelet decline in the two groups were 68 (45, 74) ×10 9/L and 62 (44, 74) ×10 9/L, respectively, with no statistically significant difference ( Z=-1.15, P=0.252). After received rhTPO treatment, the numbers of days that the two groups of patients had platelets <50×10 9/L were 7 (3, 13) d and 7 (5, 11) d, respectively, with no statistically significant difference ( Z=-1.13, P=0.281). After the patients received radiotherapy, rhTPO was started when the platelet count dropped to <75×10 9/L. The number of days required to recover to 75×10 9/L was 4 (2, 10) d in the radiotherapy alone group and 4 (2, 8) d in the concurrent chemoradiotherapy group, with no statistically significant difference ( Z=-1.07, P=0.285) ; the number of days required for platelets to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L was 8 (6, 14) d in the radiotherapy alone group and 11 (8, 16) d in the concurrent chemoradiotherapy group. The recovery time of the concurrent chemoradiotherapy group was longer than that of the radiotherapy alone group ( Z=-3.64, P<0.001). Regardless of the baseline level, there was no statistically significant difference in the number of days for platelets to recover to 75×10 9/L after rhTPO treatment between the radiotherapy alone group and the concurrent chemoradiotherapy group ( Z=-1.42, P=0.155; Z=-0.97, P=0.332). The number of days required for the two groups of patients to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L were 8 (6, 14) d and 11 (8, 16) d, respectively, with a statistically significant difference ( Z=-3.64, P<0.001). The numbers of days required for the two groups of patients with baseline platelets ≥50×10 9/L to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L were 8 (4, 12) d and 10 (8, 16) d, respectively, with a statistically significant difference ( Z=-3.12, P=0.002). However, there was no statistically significant difference in the number of days required for the two groups of patients with baseline platelets <50×10 9/L to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L ( Z=-1.88, P=0.061). The total platelet elevation rate of rhTPO within 20 days of radiotherapy treatment for both groups of patients was 93.63% (191/204), of which 95.05% (96/101) was for radiotherapy alone and 92.23% (95/103) for concurrent chemoradiotherapy, with no statistically significant difference ( χ2=0.68, P=0.410). In addition, there was no statistically significant difference in gender ( χ2=3.47, P=0.063), age ( χ2=2.79, P=0.095), TNM staging ( χ2=5.07, P=0.167), and baseline platelet count ( χ2=0.62, P=0.822) between the two groups.During the radiotherapy cycle, 27 patients (13.23%) received blood platelet infusion, and 158 patients (77.45%) completed the radiotherapy plan without interruption. No rhTPO-related adverse reactions were found. Conclusion:rhTPO in the treatment for RIT can effectively promote the recovery of blood platelet without any adverse reactions, and has good safety.

Objective:To investigate the association between CITP/MMP-1 ratio and the severity of Myocardial fibrosis (MF) in patients with Chronic Heart failure (CHF) and its diagnostic and prognostic value in patients with MF.Methods:A retrospective study was conducted to select 110 cases [86 males, (56.60±11.15) years old;24 females, (60.06±12.02) years old] who were hospitalized in the Department of Cardiology, Teda International Cardiovascular Hospital from May 18, 2021 to February 30, 2022 and underwent magnetic magnetic examination. Serum CITP and MMP-1 were detected by enzyme-linked immunoassay and CITP/MMP-1 ratio was calculated. Plasma brain natriuretic peptide (BNP) was detected by automatic chemiluminescence analyzer. Anova and non-parametric test were used to compare the difference of indexes among all groups. Spearman analysis was used to analyze the correlation between serum collagen metabolites and the severity of myocardial fibrosis. Logistic regression analysis was performed for multivariate analysis, and ROC curve was used to evaluate the auxiliary diagnostic value of related indexes. Major adverse cardiac events within 1 year after discharge were recorded, including cardiogenic death, HF rehospitalization, malignant arrhythmia, and myocardial infarction. The risk factors of poor prognosis were analyzed by Cox regression. Patients were divided by the median value of CITP/MMP-1 ratio or the median value of CITP/MMP-1 ratio and BNP. Survival analysis was performed by Kaplan-Meier and Log Rank test was performed.Results:Serum MMP-1 and BNP in LGE (+) group were higher than those in LGE (-) group (1.79 ng/ml > 0.91 ng/ml, Z=-2.924; 503 pg/ml > 367 pg/ml, Z=-1.932; P<0.05); The CITP/MMP-1 ratio in the LGE (+) group was lower than that in the LGE (-) group (3.84 < 10.85, Z=-3.601, P<0.001). MMP-1 in CHF with arrhythmia group was higher than that in CHF group (1.98 ng/ml > 1.25 ng/ml, Z=-2.016), while CITP/MMP-1 ratio was lower than that in CHF group (3.25 < 5.73, Z=-2.751), all P<0.05. CITP/MMP-1 ratio in CHF patients was negatively correlated with the severity of MF ( r=-0.363, P<0.001), and BNP and MMP-1 were positively correlated with the severity of MF ( r=0.267, r=0.264, P<0.05). Serum BNP was positively correlated with collagen metabolite MMP-1 and negatively correlated with CITP/MMP-1 ratio (all P<0.05). Logistic multivariate regression analysis showed that only CITP/MMP-1 was a predictor of myocardial fibrosis, with an OR value of 0.624 ( P=0.005). ROC curve was used to evaluate serum BNP, MMP-1 and CITP/MMP-1 ratio in the diagnosis of myocardial fibrosis in HF patients, with AUC of 0.653, 0.696 and 0.754, respectively. The accuracy of CITP/MMP-1 ratio in diagnosing fibrosis was better than that of BNP by comparing their AUC, and the difference was statistically significant ( Z=-3.808, P<0.001). Cox regression analysis showed that CITP/MMP-1 ≤3.84 was a risk factor for poor prognosis, OR=2.647 ( P=0.009). Kaplan-Meier survival analysis at 1-year follow-up showed that the survival rate of the group with lower CITP/MMP-1 ratio was significantly lower than that of the group with higher CITP/MMP-1 ratio ( P=0.014). The survival rate of CITP/MMP-1 increased and BNP decreased group was higher than that of CITP/MMP-1 decreased and BNP increased group ( P=0.011). Conclusions:The ratio of CITP/MMP-1 can be used as a negative correlation indicator of the degree of cross-linking, which is better than BNP in the evaluation of MF, and has a good auxiliary diagnostic value for myocardial fibrosis in patients with chronic heart failure, and is expected to become a protective indicator for patients with chronic heart failure and be used in clinical evaluation of myocardial fibrosis. CITP/MMP-1 ratio is associated with the incidence of major adverse cardiac events, and CITP/MMP-1 ≤3.84 can be used as a predictor of prognostic adverse cardiovascular events in CHF patients.

Objective:To analyze the clinical characteristics and predictive factors of SSc associated heart disease.Methods:The clinical data of patients with SSc from January 2016 to December 2021 in Ningbo Medical Center Lihuili Hospital were collected. Aight healthy controls come from the medicial examination center. They were divided into a positive group and a negative group based on whether heart involvement was present or not. The clinical manifestations of the two groups were compared by t test, Wilcoxon signed rank test and χ2 test and Logistic regression or ROC curve was used to analyze the prognostic risk of SSc associated heart disease. Then the transcriptome sequencing was used to analyze the differential gene expression. Results:①A total of 75 SSc patients were treated in our hospital, of which 6 patients with overlap syndrome and 1 patient with congenital heart disease were excluded. The clinical data of 68 patients were analyzed including 16 patients in the positive group and 52 patients in the negative group. Among the 16 patients with cardiac involvement, 12 patients (75.0%) had abnormal electrocardiogram, 9 patients (56.2%) with heart valve disease, 8 patients (50.0%) with abnormal cardiac structure and 8 patients (50.0%) with pericardial effusion. The biomarkers were elevated in 10 cases (83.3%). ②Univariate analysis showed that the positive group had a longer course of disease [120(11.2, 132) months vs 48(24, 90)months, Z=-2.08, P=0.037], and the rate of pulmonary arterial hypertension (50.0% vs 11.5%, χ2=11.07, P<0.001) and renal insufficiency(50.0% vs 3.8%, χ2=20.78, P<0.001) in the positive group were significantly higher than those in the negative group. Further Logistic regression analysis revealed that long course of disease [ OR (95% CI) =1.011 (1.001, 1.021), P=0.031], pulmonary arterial hypertension [ OR (95% CI) =5.431, 95% CI (1.065, 27.710), P=0.042] and renal insufficiency [ OR (95% CI) =30.444 (4.139, 223.938), P<0.001] were risk factors for SSc associated heart disease. ③Nail-fold videocapillaroscopy (NVC) was checked in 63 patients. The difference of abnormal NVC changes between the two groups was statistically significant (93.3% vs 58.3%, χ2=5.87, P=0.013). The total number of capillaries in the positive group was significantly less than that in the negative group [3.5(2, 4.8) vs 6 (5, 7), Z=-2.97, P=0.003]. Further ROC curve analysis showed that the total number of capillaries less than 4.5 predicted the occurrence of cardiac involvement (sensitivity was 80.0%, specificity was 83.8%), and the area under the ROC curve (95% CI) was 0.805 (0.061, 1.000, P=0.003).④The transcriptome of a total of 11 SSc patients (including 6 in the positive group and 5 in the negative group) and 8 healthy controls were analyzed to obtain the synchronously down regulated gene TNFRSF13B. The differences between the three groups were statistically significant ( χ2=11.88, P=0.003), especially in the positive group and the healthy controls( χ2=11.19, P=0.004). Conclusion:SSc patients with long course of disease accompanied by PAH and renal insufficiency are prone to have heart involvement. Early capillary endoscopy is also helpful to predict the risk of heart involvement. Moreover, TNFRSF13B genetic testing is helpful but further study is needed.

Objective:To explore the applicability of the distance between facial marks classification in evaluating the severity of androgenic alopecia in men.Methods:From June to December 2019, the male Chinese with diagnosis of androgenic alopecia were evaluated in the specific clinic of alopecia of Hangzhou First People’s Hospital according to the distance between facial marks and BASP(basic and specific) classification. The classification based on the distance between facial marks measures the distance from the facial marks of the anterior hairline to the horizontal line of the eyebrow and the longest radius of hair loss in the hair rotation center, the hair recession of the patient’s forehead (F), temporal (M) and vertex (V) parts. The hair loss in each region is rated as 0-3 grade from light to heavy, and the final hair loss grading is expressed as FnMnVn, such as F1M2V0. The highest grade of hair loss in F, M and V is the overall grade of hair loss. SPSS 25.0 software was used to statistically analyze the general data of patients, and Kappa test was used to evaluate the consistency between the results of the distance classification and BASP classification. The repeatability of the distance classification was tested by the repetition rate of three hair loss specialists. When two or more specialists gave the same evaluation among the three hair loss specialists, the result was regarded as the standard result. The ease of use of the distance between facial marks classification was tested by the consistency rate between the grading results of two temporary trained general doctors and the standard results.Results:A total of 150 male patients, aged (32.8±7.9) years (19-58 years), were included, of which 99 patients were 24-35 years old, accounting for 66.00%. It can be observed that the onset age was earlier. As assessed in this classification, the patients who participated in the study were graded as mild in 65 cases(43.33%), severe in 58 cases(38.67%), and moderate, which was consistency with the results obtained by BASP classification ( κ=0.573, P<0.001). Three experienced alopecia specialists evaluated 150 patients through the distance between facial marks. The results showed that the repetition rates of frontal, temporal and parietal classification results were 98.00%(147/150), 97.33%(146/150) and 96.00%(144/150), respectively. The repetition rate of the final alopecia classification was 92.00%(138/150), and the repetition rate of the overall alopecia classification was 98.00%(147/150). The consistency rate between the overall alopecia classification results of two temporary trained general doctors and the standard results was 95.92%(141/147) and 96.60%(142/147), respectively, and the consistency rate of the other results was higher than 90.00% except for one general doctor who was 89.86%(124/138) in the final classification. Conclusion:The distance between facial marks classification is a comparatively accurate and easy-to-learn grading method designed for Chinese male androgenic hair loss patients based on objective measurement data.