Objective The myocardial injury was induced by hypobaric hypoxia through regulating the expression of various proteins.The expression of proteins was mainly detected by western blot,but the selection of internal reference proteins and their variations have not been systematically studied.Methods Myocardial injury was induced in a low-pressure,low-oxygen chamber simulating an altitude of 6000 m,for 24 and 72 h.Establishment of the myocardial injury model was confirmed by hematoxylin eosin(HE)staining.Expression levels of internal control proteins,including vinculin,α-tubulin,eukaryotic translation initiation factor-5(EIF5),β-actin,glyceraldehyde-3-phosphate dehydrogenase(GAPDH),cyclophilin B,and cofilin,were detected by Western Blot and total protein expression was detected by Ponceau S and Coomassie Blue staining.An adult mouse cardiomyocytes(AMCMs)injury model was induced by hypoxia for 12 and 24 h and confirmed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL staining).Internal control proteins were detected by Western Blot,as in the in vivo model,and total protein expression was detected by Ponceau S and Coomassie Blue staining.Results A myocardial injury model was established by hypobaric hypoxia for 24 and 72 h,the total protein expression levels remained consistent.The expression of internal control proteins including vinculin,EIF5,β-actin,cyclophilin B,and cofilin was consistent between the control and model groups.Expression levels of α-tubulin were similar in the plain control and 24 h hypobaric hypoxia group,but were significantly lower in the 72 h hypobaric hypoxia group compared with the plain control group.GAPDH expression was significantly higher in the 24 and 72 h hypobaric hypoxia groups than in the plain control group.An AMCM injury model was established by hypoxia for 12 and 24 h.Total protein levels and expression levels of the internal control proteins EIF5 and β-actin were consistent,but vinculin,α-tubulin,GAPDH,cyclophilin B,and cofilin expression levels were higher in both hypoxia groups compared with the normoxic control group.Conclusions EIF5 and β-actin may be the suitable loading control proteins for studies of hypobaric hypoxia-induced myocardial injury using Western Blot.Total protein is also a good choice for hypobaric hypoxia studies.

Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P＞0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.

Objective To explore the efficacy and safety of dapagliflozin in patients with paroxysmal atrial fibrillation (PAF) combined with heart failure with preserved ejection fraction (HFpEF). Methods A total of 120 patients with PAF combined with HFpEF treated at Jinshan Hospital of Fudan University from July 2022 to July 2023 were selected and randomly divided into the dapagliflozin group (n＝60, standard treatment combined with dapagliflozin) and the control group (n＝60, standard treatment combined with placebo). After 12 months of follow-up, the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS), PAF duration, recurrence rate and frequency of PAF, left atrial diameter, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction, P-wave dispersion, blood pressure, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), and glycated hemoglobin A_1C (HbA_1C) were compared between the two groups. Cardiovascular outcomes and adverse events were observed. Results A total of 10 patients lost to follow-up, and 110 patients were included in the analysis (55 in each group). After 12 months of treatment, the KCCQ-TSS in the dapagliflozin group was significantly higher than that in the control group ([61.68±2.65] points vs [44.98±4.76] points, P＜0.001). The PAF duration in the dapagliflozin group was significantly shorter than that in the control group ([144±18] min vs [270±24] min, P＝0.045). After treatment, frequency of PAF, NT-proBNP levels, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left atrial diameter, P-wave dispersion, and HbA_1C levels showed statistical differences between the two groups (P＜0.05). The heart failure readmission rate and PAF recurrence rate in the dapagliflozin group were significantly lower than those in the control group (P＜0.05). There was no significant difference in the incidence of adverse events between the two groups during treatment. Conclusions Dapagliflozin improves patients’ quality of life, reduces PAF duration and recurrence rate, decreases heart failure readmission rate, lowers NT-proBNP levels, reverses cardiac remodeling, and demonstrates favorable safety in patients with PAF combined with HFpEF.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Objective:To summarize the clinical characteristics of plaque psoriasis patients with thrombocytopenia, and to evaluate the efficacy and safety of biologics in such patients.Methods:A single-center retrospective cohort study was conducted. Clinical data were collected from plaque psoriasis patients with thrombocytopenia at the Department of Dermatology, Peking University Third Hospital between January 2017 and October 2024. Comparative analysis was conducted on clinical data, such as platelet counts, before and after the use of biologics, and the efficacy and safety of biologics were evaluated.Results:Eleven patients (10 males, 1 female; age range: 33 - 72 years) had thrombocytopenia prior to biologic therapy. Thrombocytopenia was caused by hypersplenism secondary to liver cirrhosis in 7 patients, and the causes of cirrhosis including prior medications for psoriasis (5 cases) and viral hepatitis (2 cases) ; 3 patients were diagnosed with primary immune thrombocytopenia (ITP), and 1 patient with aplastic anemia. All the 11 patients achieved a Psoriasis Area and Severity Index (PASI) 90 response after biologic therapy. Only one patient experienced a transient episode of further decrease in platelet counts, which was considered potentially related to anti-tuberculosis drugs. The Wilcoxon signed-rank test showed no significant decrease in platelet counts after biologic therapy in the 11 patients (pre-treatment platelet counts M [ Q1, Q3]: 77 [55, 87] × 10 9/L, post-treatment platelet counts: 84 [65, 114] × 10 9/L, P = 0.083) ; notably, 3 patients with ITP showed an upward trend in platelet counts after treatment with interleukin (IL) -17A or IL-23 inhibitors. Conclusions:Thrombocytopenia may not be a contraindication for biologic therapy in patients with plaque psoriasis. Plaque psoriasis patients with ITP may obtain dual benefits from the use of IL-17A inhibitors or IL-23 inhibitors.

Objective:To explore the clinical and genetic characteristics of dyskeratosis congenita (DC).Methods:A retrospective analysis was conducted on the clinical, laboratory, imaging, pathological, genetic, and treatment data of 6 DC patients diagnosed at the Children′s Hospital of Zhejiang University School of Medicine from January 2010 to June 2025.Results:Among the 6 DC patients, 1 case was of Hoyeraal-Hreidarsson syndrome, 4 were male, and 2 were female. The diagnosis age 0.9-6.1 years. All 6 cases presented with bone marrow failure; 5 cases had a classic triad of skin and mucous membrane (mucosal leukoplakia, abnormal skin pigmentation, nail dystrophy); 5 cases had growth retardation, among which 2 cases had intrauterine growth retardation. Two cases had diarrhea and 1 case had abnormal liver function; 1 case had stiff and deformed limbs, accompanied by limited mobility, and dry and obstructive balanitis; 1 case had recurrent eyelid inflammation, middle ear inflammation, and nasal inflammation. All 6 cases had decreased B cell numbers, and 4 cases also had decreased natural killer cell numbers. There were 3 cases of children with cytomegalovirus (CMV) infection, of which 1 case of CMV infection led to retinal frosted branch angiitis and subsequent intracranial CMV infection resulting in death, and 1 case had CMV enteritis and died of hemophagocytic syndrome. Among 4 cases of boys, 3 cases had DKC1 gene variations and 1 case had an unknown variation gene; 2 cases of girls had TINF2 gene variations. The TINF2 c.860T>A (p.L287Q) variation site was a new mutation. Among 6 patients with DC, 2 cases died, 3 cases survived and 1 case was lost to follow-up.Conclusions:The DKC1 and TINF2 genes are common pathogenic genes in patients with DC. Bone marrow failure is a clue for the early identification of DC. The triad of skin and mucous membrane is its typical clinical manifestation. Children with DC generally have reduced B cells and natural killer killer cells, and have a high risk of fatal CMV infection. The overall prognosis is poor.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Objective:To construct an assessment model for operational quality of medical equipment by adopting Driving Force-Pressure-State-Impact-Response(DPSIR)model,and analyze its application value in operational management for medical equipment.Methods:The DPSIR model was adopted to formulate 20 evaluation indicators from five dimensions:driving force,pressure,state,influence and response.The evaluation indicators were evaluated by using composite weight method.According to the evaluation results,the management process of medical equipment was improved to achieve the optimal allocation for medical equipment.A total of 442 medical equipment in clinical use at Nanjing Brain Hospital from January 2022 to December 2023 were selected,and they were randomly divided into a conventional management mode group(221 equipment)and an assessment model mode group for operational quality of medical equipment by using DPSIR(221 equipment,model management mode group).The management quality of equipment operation,management efficiency and safety of using equipment between the two management modes were compared.A self-made questionnaire was used to investigate the satisfaction scores of managers for equipment,clinicians and clinical nurses on the clinical services of the equipment under the two management modes.Results:The scores of the standardization degrees of equipment operation,cleaning and disinfection,maintenance and repairing fault of adopting the model management mode were respectively(93.25±4.69),(93.47±5.36),(91.48±4.59)and(93.44±4.98),all of which were higher than those of adopting the conventional management mode,and the differences were statistically significant(t=15.489,12.920,10.905,16.354,P<0.05).The average utilization rate,stability rate of quality,and effective rate of diagnosis and treatment of the equipment of adopting the model management mode were(92.36±3.65)%,(90.58±4.36)%and(93.47±4.69)%,all of which were higher than those of adopting the conventional management mode,and the differences were statistically significant(t=12.376,10.726,11.721,P<0.05).The satisfaction scores of managers for equipment,clinicians and nurses for adopting the model management mode were higher than those of adopting the conventional management mode,and the differences were statistically significant(t=12.376,10.726,11.721,P<0.05).The incidence rates of corresponding infections,pressure-related injuries and risks caused by operation problems of equipment in adopting the model management mode were significantly lower than those in adopting the conventional management mode,and the differences were statistically significant(x2=12.280,15.000,14.141,P<0.05).Conclusion:The assessment model based on DPSIR for operational quality of medical equipment can enhance the management efficiency for medical equipment,and improve the satisfaction of users in using equipment,and raise the quality and level of management for equipment.

Laccases (LACs), belonging to the multicopper oxidase family, are closely associated with various biological functions including lignin synthesis and responses to biotic and abiotic stresses in plants. However, few studies have reported the laccase genes in China rose (Rosa chinensis). Prickles cause difficulties to the management and harvest of R. chinensis and have become a trait concerned in the breeding. To investigate the expression patterns of laccase genes in roses, we cloned a laccase gene from an ancient variety R. chinensis 'Old Blush' and named it RcLAC15. The expression level of RcLAC15 in prickles was significantly higher than those in roots, stems, and leaves. Fifty-eight laccase genes were identified in the genome of R. chinensis, and bioinformatics analysis revealed that RcLAC15 was a homolog of AtLAC15, predicting that RcLAC15 was a stable hydrophilic protein without transmembrane structures. The recombinant expression vector pBI121-proRcLAC15:: GUS was introduced into Arabidopsis, and GUS staining results showed that the RcLAC15 promoter specifically drove GUS gene expression at the edges of Arabidopsis leaves. In summary, RcLAC15 is a gene specifically expressed in the prickles of R. chinensis. This discovery provides a reference for exploring the biological functions of laccase genes in the prickles of R. chinensis.
Laccase/metabolism* ; Rosa/enzymology* ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Arabidopsis/metabolism* ; Plants, Genetically Modified/metabolism*