[Objective]To elucidate the pathogenesis of acquired aplastic anemia(AA)by integrating the traditional Chinese medicine(TCM)theory of"congenital deficiency and acquired malnourishment"with contemporary medical advancements.[Methods]Based on the etiological and pathogenesis theory of"congenital deficiency and acquired malnourishment"in TCM,combined with the research results of genetics,immunology,epigenetics,metabolism and other studies of modern medicine,this paper systematically discusses the specific mechanisms of"congenital deficiency",such as genetic predisposition factors and germline mutations,and"acquired malnourishment",such as lifestyle,environmental factors,immune abnormalities,metabolic and epigenetic abnormalities,and analyzes their association with disease onset,progression and treatment response.[Results]Studies have revealed that the occurrence of acquired AA is the result of the combined effect of"congenital deficiency"and"acquired malnourishment".The generalized concept of"congenital deficiency"encompasses non-pathogenic germline genetic variations,such as specific human leukocyte antigen(HLA)haplotypes,heterozygous mutations in genes like Fanconi anemia nucleotide-core complex(FANC)that significantly influence disease susceptibility,response to immunosuppressive therapy(IST),and risk of malignant transformation."Acquired malnourishment"manifests as environmental factor,such as proximity to chemical plants,newly renovated residences,lifestyle including high-fat diet,chronic sleep deprivation,consumption of contaminated water and infectious risk factors.These factors trigger hematopoietic failure through mechanisms including somatic mutations,epigenetic dysregulation involving DNA methyltransferase 3A(DNMT3A),ten-eleven translocation 2(TET2),metabolic disturbances,immune imbalance and gut microbiota dysbiosis,acting alone or synergistically with genetic susceptibility(the"Two-Hit"theory).In treatment,it is necessary to take into account both congenital deficiency and acquired malnourishment:for the"congenital deficiency"caused by germ line mutations(caused by germ line mutations),it is recommended that transplant intervention should be considered for key germline mutations,and transplantation should be considered for key germline mutations.In response to"acquired malnourishment",TCM shows multi-target treatment by improving telomerase through"nourishing the kidney"and"strengthening the spleen"to regulate immune,metabolism and microbiota combined with lifestyle intervention.[Conclusion]A profound understanding of the multidimensional mechanisms underlying the generalized concepts of"congenital deficiency"and"acquired malnourishment"is crucial for precision diagnostics and therapeutics,including optimizing transplant indications and developing targeted TCM/western integrated interventions to improve prognosis.Future research necessitates the integration of disease differentiation and syndrome differentiation to advance personalized treatment strategies.

[Objective]To elucidate the pathogenesis of acquired aplastic anemia(AA)by integrating the traditional Chinese medicine(TCM)theory of"congenital deficiency and acquired malnourishment"with contemporary medical advancements.[Methods]Based on the etiological and pathogenesis theory of"congenital deficiency and acquired malnourishment"in TCM,combined with the research results of genetics,immunology,epigenetics,metabolism and other studies of modern medicine,this paper systematically discusses the specific mechanisms of"congenital deficiency",such as genetic predisposition factors and germline mutations,and"acquired malnourishment",such as lifestyle,environmental factors,immune abnormalities,metabolic and epigenetic abnormalities,and analyzes their association with disease onset,progression and treatment response.[Results]Studies have revealed that the occurrence of acquired AA is the result of the combined effect of"congenital deficiency"and"acquired malnourishment".The generalized concept of"congenital deficiency"encompasses non-pathogenic germline genetic variations,such as specific human leukocyte antigen(HLA)haplotypes,heterozygous mutations in genes like Fanconi anemia nucleotide-core complex(FANC)that significantly influence disease susceptibility,response to immunosuppressive therapy(IST),and risk of malignant transformation."Acquired malnourishment"manifests as environmental factor,such as proximity to chemical plants,newly renovated residences,lifestyle including high-fat diet,chronic sleep deprivation,consumption of contaminated water and infectious risk factors.These factors trigger hematopoietic failure through mechanisms including somatic mutations,epigenetic dysregulation involving DNA methyltransferase 3A(DNMT3A),ten-eleven translocation 2(TET2),metabolic disturbances,immune imbalance and gut microbiota dysbiosis,acting alone or synergistically with genetic susceptibility(the"Two-Hit"theory).In treatment,it is necessary to take into account both congenital deficiency and acquired malnourishment:for the"congenital deficiency"caused by germ line mutations(caused by germ line mutations),it is recommended that transplant intervention should be considered for key germline mutations,and transplantation should be considered for key germline mutations.In response to"acquired malnourishment",TCM shows multi-target treatment by improving telomerase through"nourishing the kidney"and"strengthening the spleen"to regulate immune,metabolism and microbiota combined with lifestyle intervention.[Conclusion]A profound understanding of the multidimensional mechanisms underlying the generalized concepts of"congenital deficiency"and"acquired malnourishment"is crucial for precision diagnostics and therapeutics,including optimizing transplant indications and developing targeted TCM/western integrated interventions to improve prognosis.Future research necessitates the integration of disease differentiation and syndrome differentiation to advance personalized treatment strategies.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Background:This study aimed to investigate the changes in the clinical indicators and influencing factors of treatment duration among human immunodeficiency virus (HIV) patients in whom antiretroviral therapy (ART) was unsuccessful.Methods:In this retrospective study,a total of 9,418 HIV patients who failed in ART during 2004-2016 were included and divided into two treatment groups-Group 1 (treatment time ≤ 3 years,n1 =5,218) and Group 2 (treatment time ＞ 3 years,n2 =4,200).Patient follow-up data,including age,cluster of differentiation 4 (CD4) count,and viral load,glucose,creatinine,and triglyceride levels,were extracted from electronic health record databases.Covariance analysis for repeated measures was used to analyze the biochemical indicators,and multiple logistic regression modeling was used to compare relevant data extracted from the Group 1 and Group 2 HIV patient cohorts with different treatment time.Results:The median initial CD4 count was 175.0 cells/μl (interquartile range,77.0-282.0),while the initial CD4 counts for Group 1 were lower than those for Group 2 (P ＜ 0.05).A significant interaction between group and time effects was observed (P ＜ 0.05) in total cholesterol (TC).Changes in hemoglobin level among HIV patients were also significantly associated with treatment time (P =0.001).The initial CD4 count (odds ratio [OR] =0.756),female sex (OR =0.713),Zerit (d4T) (OR =1.443),TC (OR =1.285),and aspartate aminotransferase level (OR =1.002) were significantly associated with the survival time of dead patients with HIV (P ＜ 0.05).Additionally,the initial CD4 count (OR =1.456),age (OR =1.022),time interval (OR =0.903),patient's living status (OR =0.597),d4T (OR =2.256),and triglyceride (OR =0.930) and hemoglobin levels (OR =0.997) were significantly associated with the treatment time of HIV patients with drug withdrawal (P ＜ 0.05).Conclusion:The initial biochemical parameters can affect the survival and treatment time of HIV patients.With a comprehensive understanding of the physiological and biochemical indicators of patients,we can reduce the probability of drug withdrawal and prolong the survival time of HIV patients.

Objective To compare the phenylalanine(Phe)concentration in the sample of dried blood spot,measured by four different methods:fluorescence assay,tandem mass spectrometry(MS/MS), including MS/MS Derivatized,MS/MS Non-Derivatized and MS/MS-Standard Curve.Methods A total of 204 dried blood spot(DBS)samples of phenylketonuria(PKU)patients from Shanghai Xinhua Hospital were collected in this study.Phe concentration in DBS was measured by fluorescence assay and MS /MS assay,including MS/MS Derivatized, MS/MS Non-Derivatized and MS/MS-Standard Curve.The samples were divided into low, middle and high concentration groups according to Phe concentration, which were under the 360 μmol/L,between 360 and 600 μmol/L,and over 600 μmol/L respectively.The differences among the groups were analyzed by consistency check and non-parametric test.Results The within-day and between-day precisions of MS/MS-Standard Curve assay were 4.0%-7.2%,the recoveries were 93.2%-97.3%.Consistency check showed that less than 8.1%of Phe value were out of the 95%limit of agreement among these four methods.In the low and middle concentration groups,the quartile of Phe value measured by fluorescence assay,MS/MS Standard Curve and MS/MS Derivatized were 176(118,251)μmol/L,174 (94,273)μmol/L,153(94,242)μmol/L; and 540(478,578)μmol/L,485(414,529)μmol/L,466(402,513)μmol/L,respectively.Phe value measured by fluorescence assay was significantly higher than that by MS/MS Standard Curve,the difference was 4.8%-9.0%,(Z=-3.787 to -2.674,P<0.01). Phe value obtained from MS/MS Non-Derivatized was less than that by MS/MS-Standard Curve, the difference was 3.9%-5.2%,(Z=-7.474 to -5.747,P<0.01).In the high concentration group,the quartile of Phe value measured by MS/MS-Standard Curve, MS/MS Derivatized, MS/MS Non-Derivatized and fluorescence assay were 807(695,924)μmol/L,700(575,785)μmol/L,680(623,771)μmol/L and 711(674, 794)μmol/L, respectively.Phe value obtained from MS/MS Standard Curve was significantly higher than those from the other methods and the difference was 10.9% -16.2%,(Z=-4.458 to-4.356,P<0.01).Conclusions The MS/MS Standard Curve assay showed good specificity and accuracy.These four assays displayed good agreement.Although there was difference in measuring the Phe concentration among these methods, they could be used in blood Phe concentration monitoring for PKU patients.

Objective To analyze the status, trends and issues of professionals in rehabilitation institutions in China, and provide policy recommendations on rehabilitation professional development.Methods The data from database and statistical bulletin of CDPF has been analyzed using descriptive analysis and deviation analysis.Results The quantity of professionals of rehabilitation institutions increased 24,900 (12.62%) in 2016. Average professionals per institution had been decreased from 33.89 in 2012 to 28.33 in 2016. In regard to the structure of distribution, the rehabilitation professionals at provincial level had been decreased 21.95% in 2015 than that of in 2012. Both training programs and the number of trainees from rehabilitation institutions had decreased.Conclusion There were big gap between services provision and needs of professionals. The distribution of professionals at provincial, city and county level was under optimization. The on-job training for rehabilitation professionals should be improved. It is recommendated to develop national plan for professionals development to meet the needs of rehabilitation services, advance the on-job training for professionals, develop the higher education of rehabilitation and improve attractiveness of rehabilitation to retain and recruit more professionals.

Background: The rate of death among people living with HIV/AIDS has decreased significantly as a result of treatment with highly active antiretroviral therapy (HAART). However, the issues of drug induced toxicities and complexity of current HAART regimens has remained of great concern. The aim of this study was to determine factors influencing antiretroviral regimen changes among people living with HIV/AIDS in China. Methods: This retrospective study collected data through face-to-face interviews with people living with HIV/AIDS who were receiving HAART, and gathered relevant information from infectious disease hospitals. The following information were collected: social-demographic characteristics, antiretroviral therapies, CD4 cell counts, virus loads, reasons for changing medication and other related data. Mean and percentages were used to describe the frequency of regimen change among patients, and binary logistic regression was employed to test the factors influencing regimen change. Results: 1,123 people who had experienced regimen change were included in the analysis. On average, patients remained on HAART for 10.2 months before changing regimen, and the average CD4 cell count and viral load (VL) were 383.1 cells/μl and 28,132.4 copies/mL respectively when changing regimen. The reasons for modification were determined as treatment failure (52.5％), adverse reactions (32.3％), and other reasons including pregnancy (15.2％). There are significant differences in regimen change among people with different genders (P<0.001), modes of transmission (P<0.001), duration of HAART (P<0.001) and initial CD4 cell counts (P=0.0024). Males, drug users, people taking long-term medication, and those with lower initial CD4 counts when starting HAART tend to change regimen. Conclusion: Treatment failure was the main reason for the change of HAART regimen. Males, drug users, people on long-term medication and those with lower initial CD4 cell counts when starting HAART were most likely to change regimen.

Two new compounds, named lyciumlignan D () and lyciumphenyl propanoid A (), along with seven known compounds, were isolated from the root bark of. Their structures were elucidated using spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR, CD), as well as by comparison with those of the literature. Compounds-were isolated from this genus for the first time. In theassay, compounds,, andexhibited stronger anti-inflammatory effects than the positive control curcumin at a concentration of 10 μmol/L.

OBJECTIVE:To establish a method for the separation and detection of related substances in baicalein,identify its structure and preliminarily explore the degradation mechanism. METHODS:HPLC was adopted to detect the baicalein,related impurities and forced destruction of degradation products in synthesis process:the column was ES Industries? FluoroSep-RP Phenyl with mobile phase of 0.3%formic acid-methanol-acetonitrile(gradient elution)at a flow rate of 1.0 mL/min,the detection wavelength was 275 nm,the column temperature was 10℃,and the injection volume was 10μL. LC-MS/MS was conducted to identify the related substances and conjecture degradation mechanism:the column was ES Industries? FluoroSep-RP Phenyl with mobile phase of 0.3%formic acid- methanol (gradient elution)at a flow rate of 1.0 mL/min,the detection wavelength was 275 nm,column temperature was 10℃,and the injection volume was 10μL;ion source was electrospray ion source,positive and negative ions,nebulizer pressure was 55 psi and the drying gas flow was 11 L/min,drying gas temperature was 350℃,capillary voltage was 4.0 kV,detection modes were full-scan first-order MS and selective ion full-scan second-order MS,scan ranges were m/z 100-1000 (first-order MS) and 50-500(second-order MS),ionization voltage was 80-135 eV,and the collision energy was 10-30 eV. RESULTS:The linear range of baicalein was 2.4-480μg/mL(r=0.9999);RSDs of precision,stability and reproducibility tests were lower than 2.0%;the limit of quantitation was 7.2 ng,the limit of detection was 2.4 ng. Baicalein was well separated with related substance and 3 major degradation products,the related substance was chemical synthesis precursor wood butterfly;the degradation products were 6,7-quinone derivatives and 7,8-quinone derivatives,which were isomers;oxidative degradation products were benzoic acid phenyl ester derivatives. CONCLUSIONS:The main mechanisms of alkali degradation and oxidative degradation of baicalein include pyran, reciprocal rearrangement and oxidation reaction;the established method is specific and sensitive,and can be used for the detection of related substances in baicalein.

Objective:To investigate the efficacy of root canal therapy for periapical periodontitis of maxillary primary incisors accompanied by crown defects .Methods :A total of 114 children patients with periapical periodontitis of maxillary primary incisors (162) accompanied by crown defects ,who were admitted for root canal therapy during January 2010 and December 2012 ,were allocated into the caries group (85 incisors) and the trauma group(77 incisors)according to whether they had trauma history or not .Among them ,there were 75 incisors from 2‐3 years group and 87 incisors from 3‐4 years group .The efficacy analysis were conducted after one year root canal therapy with Vitapex calcium hydroxide paste from J .Morita Corporation . Results :The total cure rate was 62 .35% during one year follow‐up .The cure rate in trauma group was lower than that in the caries group ,and the difference was statistically significant (P<0 .01) .The cure rate of 2‐3 years group was lower than that of 3‐4 years group ,and the difference was statistically significant (P<0 .05) .There was no significant difference regarding cure rate among children with different genders or mobility degrees ,as well as with or without sinus(P>0 .05) .Conclusions :The long term efficacy of root canal therapy for periapical periodontitis of maxillary primary incisors with traumatic history is inferior to that for periapical periodontitis of maxillary primary incisors caused by caries .