The aging disease associated with type 2 diabetes mellitus(T2DM)is a hot research topic in the field of diabetes at present.Sarcopenia has become the third major complication of T2DM after microvascular and macrovascular diseases,which could lead to the occurrence and development of various adverse events such as fracture,disability,and dysfunction.The spleen belongs to the earth,is in the middle jiao,governs transportation and transformation,and governs muscle.The functional activities of the spleen manifesting in normal transformation and transportation,the distribution of cereal essence,and the nourishment of muscles are necessary for normal physiological functions to be exerted.Recent studies have shown that skeletal muscle cell ferroptosis plays an important role in the pathogenesis of T2DM sarcopenia.Based on the theory of"spleen governing transportation and transportation and governing muscle",this study explores the pathogenesis of T2DM sarcopenia from the perspectives of the pathogenesis of"dysfunction of spleen in transportation,deficiency of cereal essence,obstruction of dampness and turbidity,and muscle dystrophy"in traditional Chinese medicine and the pathological mechanism of"skeletal muscle cell ferroptosis"in modern medicine.It summarizes the principles of traditional Chinese medicine prevention and treatment for T2DM sarcopenia based on the spleen,to provide theoretical support for enriching the theoretical connotation of spleen visceral state,as well as basic research and clinical trials on the prevention and treatment of T2DM sarcopenia with traditional Chinese medicine.

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

OBJECTIVE: To analyze the effect of Xuezhikang on the markers of the serum lipid levels of cholesterol synthesis and absorption in early menopausal women with hypercholesterolemia, and preliminarily explore its lipid-lowering mechanism. METHODS: A total of 90 early menopausal women with hypercholesterolemia were enrolled from December, 2014 to May, 2016 from Beijing Anzhen Hospital, Capital Medical University, who were randomly allocated to receive Xuezhikang (1200 mg/d, orally) or atorvastatin (10 mg/d, orally) according to a random number table. Serum levels of some related biomarkers, including cholesterol synthesis markers (squalene, dihydrocholesterol, dehydrocholesterol, and lathosterol), and absorption markers (campesterol, stigmasterol, and sitosterol) as well as safety indices were obtained at baseline and after 8 weeks of the intervention. RESULTS: Eight weeks after treatment, both Xuezhikang and atorvastatin significantly reduced the levels of total cholesterol, triglycerides, low density cholesterol compared to baseline (all P<0.01). Xuezhikang significantly reduced the levels of squalene, dehydrocholesterol and lathosterol compared to baseline (all P<0.01), but atorvastatin only significantly reduced the level of squalene (P<0.01), compared to baseline. All cholesterol absorption markers showed no significant differences before and after treatment (P>0.05), however, a more obvious downward trend was shown in the Xuezhikang group. In addition, all the safety indices showed no significant differences between the two groups. Although the creatinekinase level in the Xuezhikang group was significantly higher, it remained within the safe range. CONCLUSIONS Xuezhikang may have more comprehensive effects on the markers of cholesterol synthesis and metabolism in early menopausal women with hypercholesterolemia through ergosterol and flavonoids in its "natural polypill."
Biomarkers ; Cholesterol ; Drugs, Chinese Herbal ; Female ; Humans ; Hypercholesterolemia/drug therapy* ; Menopause

The regulator of expression of virion(Rev)protein binds specifically to the Rev-responsive element(RRE)RNA in order to regulate the expression of the human immunodeficiency virus(HIV)-1 genes.Fluores-cence indicator displacement assays have been used to identify ligands that can inhibit the Rev-RRE interaction;however,the small fluorescence indicators cannot fully replace the Rev peptide or protein.As a result,a single rhodamine B labeled Rev(RB-Rev)model peptide was utilized in this study to develop a direct and efficient Rev-RRE inhibitor screening model.Due to photon-induced electron transfer quenching of the tryptophan residue on the RB fluorophore,the fluorescence of RB in Rev was weakened and could be dramatically reactivated by interaction with RRE RNA in ammonium acetate buffer(approximately six times).The interaction could reduce the electron transfer between tryptophan and RB,and RRE could also increase RB fluorescence.The inhibitor screening model was evaluated using three known positive Rev-RRE inhibitors,namely,proflavin,6-chloro-9-[3-(2-chloroethylamino)pro-pylamino]-2-methoxyacridine(ICR 191),and neomycin,as well as a negative drug,arginine.With the addition of the positive drugs,the fluorescence of the Rev-RRE decreased,indicating the displacement of RB-Rev.This was confirmed using atomic force microscopy(AFM)and the fluorescence was essentially unaffected by the addition of arginine.The results demonstrated that RB-Rev can be used as a fluorescent probe for recognizing small ligands that target RRE RNA.The Rev-RRE inhibitor screening model offers a novel approach to evaluating and identifying long-acting Rev inhibitors.

Objective:To summarize clinical features, diagnosis, treatment, and follow-up of children with pseudohypoaldosteronism type 1 (PHA1) and review relevant literatures to improve the understanding of the disease and reduce misdiagnosis.Methods:Six children with the main performance of salt losing treated in the Shanghai Children′s Hospital from January 2015 to December 2018, who were diagnosed as PHA1 after relevant auxiliary examinations and genetic tests.They were classified and analyzed for their treatment courses and follow-up prognosis.Results:Six children with PHA1 had varying degrees of salt losing, dehydration and infection.After the examination, 3 cases with urinary system malformations were diagnosed as secondary PHA1.Genetic testing of 2 cases revealed 2 hete-rozygous mutations c. 1439+ 1G>C and c. 875+ 1G>A in the intron region of the SCNN1A gene, and they were diagnosed as multiple target organ defect/systemic PHA1 according to American College of Medical Genetics and Genomics(ACMG) guidelines.The other case failed to be examined by genetic testing due to the refusal of parents, and was finally diagnosed as renal PHA1 according to clinical diagnosis and treatment.Conclusions:PHA1 is a rare cause of infant salt-losing syndrome, renal and secondary PHA1 children can recover quickly after sodium supplementation and the secondary factors are removed; while multiple target organ defect/systemic PHA1 has severe clinical manifestations, electrolyte imbalance is not easy to correct, and fatal arrhythmia is prone to occur, the mortality rate is high.It is easy to be misdiagnosed in clinical practice.Auxiliary examination and genetic testing can help to diagnose and classify PHA1, as well as individualized treatment.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE Paeoniflorin (PF) and albiflorin (AF) are the major active components of total peony glucosides(TPG)from Paeonia lactiflora Pal,which have many biological activities such as anti-inflammatory, antioxidation and anti-hypertension effects. The drug-drug pharmacokinetic interaction among PF,AF and TPG,the pharmacokinetic comparisons of AF between hypoxia and normoxia,the transport of AF cross the blood-brain barrier cell model and the transport of AF/PF/TPG cross Caco-2 cell model were investigated.METHODS A highly sensitive and rapid UPLC-MS method with multiple-reaction monitoring(MRM)scanning via electrospray ionization(ESI)source operating both in the positive and negative ionization mode was successfully developed and validated for simultaneous quantitation of PF and AF in rat plasma after an oral administration of PF,AF and TPG. RESULTS The validated and developed UPLC-MS/MS method was successfully applied to simultaneously determine the AF and PF concentration in rat plasma and investigate pharmacokinetic interactions after a single intragastrical ad-ministration of PF,AF,co-administration of PF with AF and TPG,respectively.The elimination of both PF co-administered with AF and PF in TPG were slower than those for PF alone and the distribution in the tissues was wider.The combination of PF with AF or TPG could significantly increase the values of the AUC, MRT and t1/2of the drug PF, and reduce the values of CL of PF. From a comparison of the main pharmacokinetic parameters among AF alone, AF combined with PF and AF in TPG, the values of the MRT and t1/2of AF in TPG were greater than that of AF alone,and there were statistically signifi-cant differences in these parameters(P<0.05,P<0.01).It was also noticed that AUC and Cmaxof PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The multiple active components in TPG may lead to DDIs between some P-gp substrates. CONCLUSION The clinical performance of total peony glucosides would be better than that of single constitute. The outcomes of the study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.

Medical history and physical examinations were performed to assess the clinical manifestations and growth of one patient with familial hypocalciuric hypercalcemia(FHH). Clinical data, including histories of his parents and 3 maternal relatives were collected. Serum parathyroid hormone(PTH), calcium, phosphorus, 24-hour urinary calcium, and 24-hour urinary calcium to creatinine ratio(UCCR)were measured or calculated. Meanwhile, after peripheral blood samples were collected and genomic DNA was extracted, the whole exome sequencing to detect gene mutations of the proband was performed. Further family screenings were also performed by Sanger sequencing to assess the relationship between genotype and phenotype. The results showed that the proband with motor developmental delays had severe hypercalcemia(4.20 mmol/L), while his mother without clinical symptoms had a higher blood calcium within the normal range(2.57 mmol/L). However, their urinary calcium levels were both low(UCCR< 0.01). The C→T heterozygous missense mutation was found by exome sequencing at nucleotide 1243 within exon 4 of calcium sensing receptor(CaSR)gene in the proband, which caused a substitution of Arginine to Tryptophan(R415W). Sanger sequencing confirmed the same mutation in his mother. There was no mutation in other family members. (Chin J Endocrinol Metab, 2018, 34: 583-586)

Objective To detect TOP2A protein expression and gene copy number alterations, and to analyze related clinical and pathological implications in pediatric neuroblastic tumors ( NT ).Methods Immunohistochemistry was used to detect TOP2A protein expression.Fluorescence in situ hybridization (FISH) was used to detect numerical aberrations of TOP2A.Results TOP2A protein was expressed in 59.1%(52/88) of cases, which was associated with differentiation (P=0.006), Ki-67 index (P<0.01) and MKI (P=0.001).Twenty-eight cases (35.0%, 28/88) showed TOP2A gene amplification, which was correlated with the age (P<0.01), clinical stage (P=0.028), high risk group (P=0.001), Ki-67 index (P=0.040) and differentiation (P=0.014).Survival analysis showed that TOP2A expression was related to survival rate.Multivariate analyses showed that TOP2A expression was an independent predictor for poor prognosis (P=0.010).Conclusions More than half of the cases show TOP2A expression, which is more likely associated with NB, high Ki-67 index and high MKI.Cases with TOP2A expression have shorter survivals and poorer prognosis.TOP2A amplification is seen in 35% and likely occurs in patients older than 18 months and at advanced INSS stages (Ⅲ and Ⅳ).As a target of the anthracycline-based adjuvant drugs, TOP2A test can be used to select patient with NT for the therapy.

We observed the effect of vibration parameters on lumbar spine under different vibration conditions using finite element analysis method in our laboratory. In this study, the CT-images of L1-L5 segments were obtained. All images were used to develop 3D geometrical model using the Mimics10. 01 (Materialise, Belgium). Then it was modified using Geomagic Studio12. 0 (Raindrop Geomagic Inc. USA). Finite element (FE) mesh model was generated by Hypermesh11. 0 (Altair Engineering, Inc. USA) and Abaqus. Abaqus was used to calculate the stress distribution of L1-L5 under different vibration conditions. It was found that in a vibration cycle, tensile stress was occurred on lumbar vertebra mainly. Stress distributed evenly and stress concentration occurred on the left rear side of the upper endplate. The stress had no obvious changes under different frequencies, but the stress was higher when amplitude was greater. In conclusion, frequency and amplitude parameters have little effect on the stress distribution in vertebra. The stress magnitude is positively correlated with the amplitude.
Biomechanical Phenomena ; Finite Element Analysis ; Humans ; Lumbar Vertebrae ; physiology ; Vibration