ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang （FFD） on mitochondrial function in the mouse model of myocardial fibrosis （MF）. MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups （n=10 per group）： control， model， low-dose， medium-dose， and high-dose （3.315， 6.63， and 13.26 g·kg^-1， respectively） FFD， and captopril （20 mg·kg^-1）. MF was induced by subcutaneous injection of isoproterenol （10 mg·kg^-1·d^-1） in other groups except the control group for 14 consecutive days， with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were measured by echocardiography. Serum levels of creatine kinase-MB （CK-MB）， cardiac troponin I （cTnI）， N-terminal pro-brain natriuretic peptide （NT-pro BNP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） levels were measured by biochemical assays. Reactive oxygen species （ROS） were detected by dihydroethidium （DHE） fluorescence staining. Hematoxylin-eosin （HE）， Masson's trichrome， and wheat germ agglutinin （WGA） staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy， adenosine triphosphate （ATP） colorimetric assay， and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit （p-AMPKα）， AMPKα， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， mitofusin 2 （MFN2）， pyruvate kinase M2 isoform （PKM2）， lactate dehydrogenase A （LDHA）， and hypoxia-inducible factor 1 alpha （HIF-1α） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited decreased LVEF and LVFS， increased heart weight index and heart weight-to-tibia length ratio （P<0.01）， elevated levels of myocardial injury markers （CK-MB， cTnI， and NT-pro BNP）， inflammatory cytokines （TNF-α， IL-1β， and IL-6）， and MDA， along with reduced SOD and GSH levels （P<0.01）. Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group （P<0.01）. Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling， crista disruption， decreased ATP content， and reduced red/green fluorescence ratio in the model group （P<0.01）. Western blot analysis demonstrated downregulation of p-AMPKα， PGC-1α， and MFN2 and upregulation of PKM2， LDHA， and HIF-1α in the model group （P<0.01）. Compared with the model group， treatment with FFD or captopril improved LVEF and LVFS， reduced heart weight index and heart weight-to-tibia length ratio （P<0.05， P<0.01）， lowered the serum levels of CK-MB， cTnI， NT-pro BNP， TNF-α， IL-1β， IL-6， and MDA， increased the SOD and GSH levels （P<0.05， P<0.01）， attenuated the myocardial fibrosis and cardiomyocyte hypertrophy （P<0.01）， and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio （P<0.05， P<0.01）. Furthermore， FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α （P<0.05， P<0.01）. ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis， thereby attenuating isoproterenol-induced myocardial fibrosis.

ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang （FFD） on mitochondrial function in the mouse model of myocardial fibrosis （MF）. MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups （n=10 per group）： control， model， low-dose， medium-dose， and high-dose （3.315， 6.63， and 13.26 g·kg^-1， respectively） FFD， and captopril （20 mg·kg^-1）. MF was induced by subcutaneous injection of isoproterenol （10 mg·kg^-1·d^-1） in other groups except the control group for 14 consecutive days， with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were measured by echocardiography. Serum levels of creatine kinase-MB （CK-MB）， cardiac troponin I （cTnI）， N-terminal pro-brain natriuretic peptide （NT-pro BNP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） levels were measured by biochemical assays. Reactive oxygen species （ROS） were detected by dihydroethidium （DHE） fluorescence staining. Hematoxylin-eosin （HE）， Masson's trichrome， and wheat germ agglutinin （WGA） staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy， adenosine triphosphate （ATP） colorimetric assay， and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit （p-AMPKα）， AMPKα， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， mitofusin 2 （MFN2）， pyruvate kinase M2 isoform （PKM2）， lactate dehydrogenase A （LDHA）， and hypoxia-inducible factor 1 alpha （HIF-1α） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited decreased LVEF and LVFS， increased heart weight index and heart weight-to-tibia length ratio （P<0.01）， elevated levels of myocardial injury markers （CK-MB， cTnI， and NT-pro BNP）， inflammatory cytokines （TNF-α， IL-1β， and IL-6）， and MDA， along with reduced SOD and GSH levels （P<0.01）. Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group （P<0.01）. Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling， crista disruption， decreased ATP content， and reduced red/green fluorescence ratio in the model group （P<0.01）. Western blot analysis demonstrated downregulation of p-AMPKα， PGC-1α， and MFN2 and upregulation of PKM2， LDHA， and HIF-1α in the model group （P<0.01）. Compared with the model group， treatment with FFD or captopril improved LVEF and LVFS， reduced heart weight index and heart weight-to-tibia length ratio （P<0.05， P<0.01）， lowered the serum levels of CK-MB， cTnI， NT-pro BNP， TNF-α， IL-1β， IL-6， and MDA， increased the SOD and GSH levels （P<0.05， P<0.01）， attenuated the myocardial fibrosis and cardiomyocyte hypertrophy （P<0.01）， and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio （P<0.05， P<0.01）. Furthermore， FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α （P<0.05， P<0.01）. ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis， thereby attenuating isoproterenol-induced myocardial fibrosis.

Objective To analyze the clinical characteristics of immune checkpoint inhibitor (ICI)-related hypophysitis. Methods A retrospective analysis was conducted on patients diagnosed with ICI-related hypophysitis and treated at the Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, between January 2020 and March 2025. Clinical manifestations and prognosis of patients were analyzed. Results Eleven patients with ICI-related hypophysitis were included. The average age was (62.27±7.63) years, and 9 patients (81.82%) were male. The median time to onset was 9.1 months, and the median number of treatment cycles received was 5. The primary initial symptoms were fatigue and anorexia. Hyponatremia was present in 3 patients (27.27%). Evaluation of anterior pituitary function revealed adrenocorticotropic hormone deficiency as the most common manifestation (90.91%, 10/11), followed by hyperprolactinemia (81.82%, 9/11). Posterior pituitary function remained normal in all patients. Pituitary magnetic resonance imaging showed no abnormality in 4 patients (44.44%). Thyroid dysfunction was observed in 6 patients (54.55%), one of whom (9.09%) also exhibited pancreatic endocrine dysfunction. The average follow-up duration was 36.5 months. Eight patients (72.73%) were alive at the last follow-up. None of the patients recovered their pituitary hormone function. Conclusions Endocrine adverse events induced by ICIs can involve multiple glandular systems. Clinicians should be highly vigilant for the possibility of ICI-induced hypophysitis in patients receiving ICIs who present with symptoms such as fatigue, anorexia, and hyponatremia.

ObjectiveTo investigate the effects of Fangji Fulingtang on macrophage polarization and oxidative stress in the mouse model of myocardial fibrosis. MethodThe mouse model of myocardial fibrosis was established by subcutaneous injection of isoproterenol （ISO， 5 mg·kg^-1·d^-1）. Fifty C57BL/6J mice were randomly assigned into control （0.9% NaCl）， model （0.9% NaCl）， low- and high-dose （3.315 g·kg^-1·d^-1 and 13.26 g·kg^-1·d^-1， respectively） Fangji Fulingtang （FFD-L and FFD-H， respectively）， and metoprolol tartrate （Meto， 15 mg·kg^-1·d^-1） groups， with 10 mice each group. After 2 weeks of treatment， the heart appearance， cardiac weight index （CWI）， heart weight （HW）/tibia length （TL） ratio， and myocardial histopathological alterations were observed. Meanwhile， the serum levels of creatine kinase-MB （CK-MB）， transforming growth factor-β₁ （TGF-β₁）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6， IL-10， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） were measured by enzyme-linked immunosorbent assay （ELISA）. The expression levels of CD86 and CD206 were observed by immunohistochemical staining. ResultCompared with the model group， the FFD-L， FFD-H， and Meto groups showed improved heart appearance， decreased CWI and HW/TL ratio （P<0.01）， lowered serum levels of CK-MB， TGF-β₁， TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， and elevated IL-10 level （P<0.05）. Furthermore， the three groups showed reduced infiltration of inflammatory cells， myocardial injury， collagen deposition， and myocardial fibrosis， decreased CD86， SOD， and GSH （P<0.01）， and increased CD206 and MDA （P<0.01）. ConclusionFangji Fulingtang can mitigate ISO-induced myocardial fibrosis by regulating macrophage polarization and oxidative stress.

Objective:To investigate clinical phenotypes of type Ⅳ hereditary hemochromatosis caused by c. 430A>G heterozygous mutation of SLC40A1 gene and the correlation between genotype and phenotype, exploring ferritin cutoff value for screening.Methods:One case of type Ⅳ hereditary hemochromatosis with c. 430A>G heterozygous mutation in the SLC40A1 gene and 5 generations of their family lineage with a total of 47 members who were seen at the First Affiliated Hospital of Nanjing Medical University in July 2020 were studied for systematic clinical investigation. Thirty-nine surviving individuals were tested for ferritin, liver function, fasting plasma glucose (FPG), and sex hormones, and Sanger sequencing was performed to verify the mutation loci and to map the family tree. Spearman correlation analysis was used to explore the relationship between ferritin and other indicators, and receiver operating characteristic curves were used to calculate the ferritin cutoff value for screening for this genotype of hemochromatosis.Results:Ten patients with c. 430A>G heterozygous mutation in the SLC40A1 gene were identified among 39 family members, and five of them were diagnosed with hemochromatosis, presenting incomplete penetrance. The differences in levels of ferritin, aspartate aminotransferase (AST; both P<0.01) and FPG, as well as incidences of hypogonadotropic hypogonadism and arthritis (all P<0.05) between group of mutation positive and group negative were statistically significant, while the difference in alanine aminotransferase (ALT) was not. Spearman correlation analysis showed that, ferritin levels were significantly associated with ALT ( r=0.903), AST ( r=0.879), FPG ( r=0.782), and the incidences of hypogonadotropic hypogonadism ( r=0.798) and arthritis ( r=0.798; all P<0.01) in those with the c. 430A>G heterozygous mutation in the SLC40A1 gene. The ferritin cutoff value for screening of hereditary hemochromatosis with c. 430A>G heterozygous mutation in the SLC40A1 gene was 1 036.7 μg/L, with a sensitivity and specificity of 100% and 94.3%, respectively. Conclusion:The SLC40A1 gene c. 430A>G heterozygous mutation is closely associated with elevated levels of AST and FPG, increased incidences of hypogonadotropic hypogonadism and arthritis, and the ferritin cutoff value is a useful screening parameter.

Objective:To systematically review the effects of the traditional Chinese medicine compound based on astragalus and angelica on bone marrow suppression after chemotherapy.Methods:Randomized controlled trials (RCTs) about the traditional Chinese medicine compound based on astragalus and angelica for bone marrow suppression after chemotherapy for malignant tumors were retrieved from Cochrane Library, PubMed, Web of Science, CINAHL, OVID, SinoMed, CNKI, VIP, and Wanfang Databases. The search period was from the establishment of the database to September 2019. The literatures were screened and the data were extracted independently by two researchers and RevMan 5.3 was used for Meta-analysis.Results:Totally 15 RCTs were included, involving 1 019 patients. Meta-analysis results showed that there were statistically significant differences in peripheral blood leukocytes [ SMD=1.32; 95% CI (0.76, 1.89) ; P<0.000 01], platelets [ MD=25.05; 95% CI (8.00, 42.10) ; P=0.004], hemoglobin [ MD=24.14; 95% CI (16.34, 31.94) ; P<0.000 01] and clinical symptoms [ RR=1.38; 95% CI (1.25, 1.52) ; P<0.000 01] between the chemotherapy group, the chemotherapy combined with the western medicine group and the traditional Chinese medicine compound group. Conclusions:The traditional Chinese medicine compound based on astragalus and angelica can improve the level of peripheral blood cells, reduce bone marrow suppression, and improve clinical symptoms and quality of life of patients with cancer after chemotherapy. However, due to the low quality of the included literature and the large heterogeneity of some of the results, more rigorously designed high-quality RCTs are needed for further verification.

Two cases of solitary fibrous tumor (SFT) with endocrine manifestations as the first symptom were investigated through comprehensively reviewing their medical history and clinical records. One case of recurrent giant solitary fibrous tumor of the thoracic cavity had repeated dizziness, palpitation and limb weakness for one month. The patient had hypoglycemia accompanied with significantly decreased serum insulin, and the ratio of insulin-like growth factor Ⅱ(IGF-Ⅱ) and insulin-like growth factor Ⅰ (IGF-Ⅰ) was greater than 10. Non-islet cell tumor hypoglycemia (NICTH) should be considered in the patient. Another case was found to have thyroid gland SFT and developed distant metastasis. The patient presented with hypoglycemia, hypokalemia and possible consumptive hypothyroidism. Clinicians should improve our understanding of the endocrine manifestations of the disease. SFT may occur in endocrine glands (such as thyroid), and may also present as NICTH and consumptive hypothyroidism.

Recent studies have shown that changes in the form and color of sublingual collaterals were related to diabetes. And the changes of sublingual collaterals have certain clinical value in judging the condition, stage, treatment and prognosis of diabetes. This article summarized the research progress of sublingual collaterals from two aspects: the relationship between sublingual collaterals and diabetes mellitus and laboratory indexes, and the modern science and technology.

Objective To explore the risk factors for childhood death from pneumococcal meningitis.Methods The data of 32 hospitalized children were retrospectively analyzed,who were diagnosed as pneumococcal meningitis and enrolled in the Affiliated Children′s Hospital of Soochow University from November 201 0 to December 201 5.The subjects were divided into the death group and survival group according to their prognosis.The clinical characteristics and laboratory data were compared between 2 groups.Results Between the death group and survival group,there were significant statistically differences in shock within 24 hours after admission(63.6% vs 1 4.3%,P =0.01 3),as well as endotracheal tube intubation(1 00.0% vs 23.8%,P <0.001 ),the levels of cerebrospinal fluid(CSF)IgG[(491 .27 ± 203.53)mg/L vs (267.24 ±1 88.07)mg/L,P =0.006],IgM[(1 1 5.72 ±79.1 9)mg/L vs (32.80 ±28.52)mg/L, P =0.006],IgA[59.52(1 5.51 ,75.69)mg/L vs 1 8.77(9.33,27.54)mg/L,P =0.023],CSF leukocyte[330.00 (1 50.00,380.00)×1 06 /L vs 870.00 (403.00,6 1 60.00)×1 06 /L,P =0.009 ],CSF protein [(4 047.00 ± 1 942.1 6)mg/L vs (2 470.62 ±1 259.94)mg/L,P =0.009],CSF adenosine deaminase (ADA)[35.20(1 8.90, 87.20)U /L vs 8.80(3.05,23.78)U /L,P =0.001 ],serum sodium[(1 30.21 ±2.85)mmol/L vs (1 32.83 ±3.69) mmol/L,P =0.049],serum lactic acid (LA)[4.40 (2.60,5.70)mmol/L vs 2.40 (1 .75,4.50)mmol/L,P =0.01 3],serum C -reactive protein (CRP)[(95.87 ±65.40)mg/L vs (1 65.61 ±83.05)mg/L,P =0.022],serum lactate dehydrogenase (LDH)[81 3.40(465.20,2 31 0.70)U /L vs 359.20(257.85,405.90)U /L,P =0.001 ], platelet[(1 63.82 ±1 64.86)×1 09 /L vs (295.71 ±1 30.29)×1 09 /L,P =0.01 9]and positive rate of blood culture (90.9% vs 47.6%,P =0.023)between the death group and survival group.Conclusions The risk factors associated with mortality in pediatric SPM include shock within 24 hours after admission,endotracheal intubation,hyponatremia, thrombocytopenia,as well as high serum LA level,high serum LDH level,lower serum CRP level or cultures of blood and CSF double positive.

ObjectiveTo investigate the clinical features and prognosis of children with rotavirus gastroenteritis and convulsion.MethodsClinical data of children with rotavirus gastroenteritis hospitalized from January 2010 to December 2013 were retrospectively analyzed. Subjects were divided into the seizure group and no seizure group according to the presence of seizure in the course and compared between the two groups.ResultsThere were no signiifcant differences in sex, age, and the average duration of hospitalization between two groups (allP>0.05). The family history, history of seizures, the levels of serum sodium, calcium, lactate, standard bicarbonate concentration (SB), actual bicarbonate concentration (AB), carbon dioxide content (TCO2) and pH were statistically signiifcant between two groups (allP>0.05). During the follow-up period (outpatient telephone follow-up), the recurrence of seizure in two groups was signiifcant different (P<0.05) and only one (0.54%) child in seizure group developed epilepsy.ConclusionThis study showed that rotavirus gastroenteritis with convulsion is a benign clinical course.