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Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.
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With the development of medical technology and the deepening of medical reform, hospital laboratory test continues to expand. Affected by factors such as technology and cost, the business of outsourcing laboratory test to independent clinical laboratories develops rapidly. However, this cooperation mode has not been carried out for a long time and lacks systematic management experience. Through the analysis of the motivation of hospital delivery, this study expounds the classification, judgment basis and requirements for suppliers of third-party clinical laboratory delivery, as well as the operation practice of laboratory test delivery, so as to provide reference for more standardized and effective testing delivery for hospitals.
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Objective:The article aims to explore the positive promoting effect of the construction of a medical university’s incubation platform on the Industry-University-Institute cooperation and biomedical scientific and technological achievements transformation.Methods:Through literature review, the article studied the existing mode of Industry-University-Institute cooperation in universities, analyzed the main bottlenecks, and summarized the practical exploration experience of ″Shanghai Pharmaceuticals-SJTUSM Innovative Achievements″ incubation platform.Results:The incubation platform effectively promoted the process and system construction of the scientific and technological achievements transformation in the university, and improved the project mining level and platform support function.Conclusions:The practical exploration of the incubation platform lays a foundation for the construction of the biomedical industrial park. Through the in-depth construction of the " Government-Industry-University-Institute-Investment-Inventor" development chain, the platform can help to promote strategic innovation and industrialization of achievements, making the " first-in-class" medicine in China.
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Objective:To analyze nine cases of pregnancy and lactation-associated osteoporosis(PLO) along with a literature review to improve clinicians′ knowledge of the disease.Methods:We collected medical history, laboratory examination, bone mineral density(BMD) scan, treatment and follow-up data of 9 inpatients with PLO in the Endocrinology Department of the First Affiliated Hospital of Zhengzhou University from January 2014 to June 2021.Results:The median age of onset of 9 patients with PLO was 30 years(22-37 years). All 9 patients presented low back pain, and the median time of low back pain after childbirth was 2.5 months(0.5-7 months). 89% of the patients presented vertebral compression fractures, and the mean number of vertebral fractures was 4.6. Eight patients with PLO showed osteoporosis by dual X-ray absorpiometry(DXA) scan, and one patient showed bone loss by quantitative CT scan. Osteoporosis predominated in the trabecular bone. After the diagnosis, nine patients with PLO stopped breastfeeding and were given calcium and vitamin D preparations. Seven patients were given bisphosphonates and one patient was treated with teriparatide followed by denosumab. The back pain of all patients was relieved, with the median of relief time being 3 months(7 d-6 m). After treatment initiation, BMD was increased in eight patients, especially obvious in the lumbar spine. No new clinical fractures occurred during the follow-up.Conclusions:For women with low back pain and shortened height in late pregnancy or breastfeeding, the possibility of PLO should be considered. Prompt diagnosis and early medical interventions are of utmost importance to reduce the risk of subsequent fractures and improve the prognosis.
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Objective:To investigate the distribution of clustered regularly interspaced short palindromic repeats (CRISPR) in group B Streptococcus (GBS) in the genital tract of women during the third trimester and in infants with invasive infection and its relationship with multilocus sequence typing (MLST) and drug-resistance genes. Methods:This study retrospectively collected 84 GBS strains isolated from pregnant women with GBS colonization and infants with invasive GBS infection who were admitted to Children's Hospital Affiliated to Shanxi Medical University from January 2017 to January 2022. CRISPR, MLST, and drug-resistance phenotype and genes were detected and analyzed using χ 2 test or Fisher exact probability method. MEGA11 was used to construct a dendrogram. Results:There were ten sequence typing in the 84 GBS strains and ST10 was the dominant one (46.4%). GBS was sensitive to penicillin, and its resistance rates to erythromycin (75.0%) and clindamycin (73.8%) were high. Among the 17 invasive GBS strains, ST10 had 100% resistance to erythromycin, clindamycin, and levofloxacin. CRISPR1 gene was amplified in 62 strains (73.8%). CRISPR1-positive strains had a significantly higher proportion of ST10 [56.5%(35/62) vs 18.2%(4/22), χ 2=9.56, P=0.002] and ermB, gyrA, parC [54.8%(34/62) vs 22.7%(5/22), 67.7%(42/62) vs 36.4%(8/22), 71.0%(44/62) vs 36.4%(8/22); χ 2=6.73, 6.64, and 8.25, all P<0.05], and a lower proportion of ermA [6.5%(4/62) vs 31.8%(7/22), χ 2=7.09, P=0.008] than CRISPR1-negative strains. Conclusions:ST10 is the main GBS genotype among the colonized microbiota the genital tract of pregnant women and in infants with invasive GBS infection, which is also a dominant type in CRISPR1-positive strains. GBS is sensitive to penicillin and CRISPR1 gene is linked to the spread of some drug-resistance genes.
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In recent years, more and more studies have shown that myeloid-derived suppressor cells (MDSCs) participate in the development and progression of various chronic liver diseases including chronic viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver diseases, and liver cancer. As a type of cells derived from bone marrow progenitor cells and immature myeloid cells, MDSCs play an important role in the development, progression, and repair of liver diseases by regulating inflammatory response and the differentiation and function of immune cells. This article reviews the research advances in the association between MDSCs and various liver diseases, in order to provide new thoughts for the clinical diagnosis, prognosis, and treatment of chronic liver diseases.
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Objective:To discuss the relationship between neurofunctional prognosis and early mean arterial pressure (MAP) of patients with post-cardiac arrest syndrome (PCAS).Methods:This retrospective study enrolled 151 PCAS patients in Henan Provincial People’s Hospital between January 2016 and January 2018. A multivariate logistic regression analysis was established to determine the correlation between the MAP at the first 6 h and the prognosis of the patients at discharge. The effect of angioactive drugs on the neurofunctional prognosis of patients at discharge was determined by chi-square test.Results:The multivariate logistic regression analysis showed that the TWA-MAP of patients with good neurofunctional prognosis at discharge was significantly higher than that of patients with poor prognosis (83.25±13.69) mmHg vs (77.06±18.37) mmHg, P=0.042. In the first 6 h after ROSC, the neurofunctional prognosis of patients with good prognosis in the TWA-MAP value of 71 to 80 mmHg was significantly better than that of patients with TWA-MAP lower than 70 mmHg (11% vs 37%, P=0.009). The variable logistic regression analysis results showed that the level of TWA-MAP higher than 70 mmHg or 65 mmHg was the independent factor affecting the outcome, while the level of TWA-MAP higher than 70 mmHg had a better correlation with the neurofunctional prognosis ( OR=4.11, 95% CI:1.34-12.66, P=0.014). In patients with TWA-MAP higher than 70 mmHg, the neurofunctional prognosis of patients with good prognosis but without angioactive drugs was significantly better than that of those with angioactive drugs (48% vs 24%, P=0.010). Conclusion:Holding TWA-MAP higher than 70 mmHg in the first 6 h after PCAS is helpful to improve the neurofunctional prognosis of patients at discharge.
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Objective:To explore the differential diagnosis methods between nonclassical 21-hydroxylase deficiency(NC21-OHD) and polycystic ovary syndrome(PCOS).Methods:The clinical data of 31 women with NC21-OHD were compared with those of 29 women with PCOS.Results:Women with NC21-OHD showed a higher prevalence of adrenal hyperplasia and lower likelihood of polycystic ovary(PCO) than those with PCOS( P<0.05), with lower height( P<0.05). The levels of adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone(17-OHP), androstenedione(AD), total testosterone(TT), and progesterone were higher in women with NC21-OHD compared with those with PCOS( P<0.05). Women with PCOS had higher levels of luteinizing hormone(LH) and higher ratio of LH to follicle stimulating hormone(FSH) than those with NC21-OHD( P<0.05). The best two identification indexes for the two diseases were 17-OHP and progesterone, with the optimal cut-off points 3.34 ng/ml(sensitivity 89.7%, specificity 93.1%) and 0.64 ng/ml(sensitivity 90.0%, specificity 75.9%), respectively. During the 1-day mid-dose dexamethasone suppression test(DST), women with NC21-OHD had higher inhibition rates of 17-OHP, progesterone, AD, and TT( P<0.01) than those with PCOS. Their optimal cut-off values of suppression rates were 73.5%(sensitivity 95.2%, specificity 100.0%), 55.5%(sensitivity 100%, specificity 88.9%), 61.4%(sensitivity 84.2%, specificity 100.0%), 68.3%(sensitivity 65.0%, specificity 100.0%), respectively. Conclusion:The clinical manifestations of women with NC21-OHD are similar to those with PCOS. 17-OHP is the best differential indicator and the 1-day mid-dose DST plays an important role in the identification of the two diseases. Genetic analysis is the gold standard for distinguishing the two diseases.
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Objective:To explore the effect of combined orbicularis muscle double stitch operated on blepharoplasty.Methods:A total of 90 patients, 79 females and 11 males, aged 18-49 years, were treated by using combined orbicularis muscle double stitch procedure, that is, to fix upper lifting muscle, to remove partial fat, and to perform blepharoplasty.Results:All 90 cases' incisions were healed at the first phase, no obvious swelling and bleeding. Within 3-24 months follow up, all patients' upper eyelids were significantly improved. The skin was smoothy when closing eyes, and eyelash was up when opening eyes, and arc was natural and satisfactory.Conclusions:This method can improve the shape of the upper eyelid swelling and get long-lasting and stable physiological eyelid.
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Objective To explore the influence of cucurbitacin E (CuE) on autophagy in human bladder cancer cell line T24 and further study its impacts on cell proliferation. Methods MTT assay was used to determine the proliferation inhibition capacity of CuE on T24 and western blot to check the impacts of CuE treatment on the expression of classic autophagy markers LC3A/B and p62. LC3 turnover assay and GFP-RFP-LC3 fluorescent assay were performed to determine autophagy flux. Western-blot was used to check the autophagy inhibition ability of 3-MA on CuE treatment and MTT assay and cell counting assay were used to check the influence of CuE-induced autophagy on cell proliferation with/without autophagy inhibition. Results CuE inhibited the proliferation of T24 and the IC50 in 24 h was about 0.75 μmol/L. CuE treatment increased the expression of LC3A/B Ⅱ and LC3A/B Ⅱ/Ⅰ ratio (P < 0.05) , but decreased the expression of p62 (P < 0.05) , indicating the induction of autophagy. Autophagy flux was induced because of positive LC3 turnover assay and the increase of yellow and red dots in GFP-RFP-LC3 fluorescent assay (P < 0.05). CuE-induced autophagy was inhibited by 3-MA (P < 0.05). With autophagy inhibition, CuE's proliferation suppression ability on T24 was attenuated (P <0.05). Conclusion CuE induces autophagy in bladder cancer cell line T24 and the induced autophagy positively contributes to the inhibitation of cell proliferation.
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Objective:To detect the interleukin-22(IL-22) levels in peripheral blood of the asthma patients and analyze the relationship between the IL-22 levels and IgE,pulmonary function,fractional exhaled nitric oxide(FENO),and to investigate the role of IL-22 in the pathogenesis of bronchial asthma. Methods:Seventy-eight patients with asthma were selected as experiment group.The asthma patients were divided into increased IgE group (n=46)and normal IgE group(n=32)according to the IgE levels.The asthma patients were also divided into acute attack stage and clinical control stage according to patients' clinical symptoms.In addition, twenty healthy controls were chosen as healthy control group.The plasma IL-22 levels, IgE,forced expiratory volume in one second (FEV1) and FENO levels of the subjects in various groups were detected and compared between various groups.The correlations between the plasma IL-22 levels and IgE, FEV1,FENO were analyzed.Results:The plasma IL-22 level and FENO level of the patients in asthma group were higher than those in healthy control group(P0.05;r=0.059 8,P>0.05).Conclusion:The increased expression of IL-22 in peripheral blood of the patients with asthma may participate in the pathogenesis of asthma,and may aggravate the deterioration of pulmonary function of the asthma patients.
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OBJECTIVE:To observe clinical efficacy and safety of Brucea javanica oil combined with gemcitabine and cisplat-in in the treatment of advanced non small cell lung cancer(NSCLC). METHODS:Totally 131 advanced NSCLC patients selected from Huanggang Hospital of TCM during Feb. 2014 to Jan. 2016 were divided into observation group(71 cases)and control group (60 cases)according to random number table. Control group was given Gemcitabine for injection(1st and 8th day)+Cisplatin injec-tion (2nd day),every 21 days,twice as a treatment course. Observation group was additionally given Breucea javanica oil oral emulsion 20 mL,po,2-3 times/d,for consecutive 14 d (3 days before chemotherapy). Both groups received treatment for 87 d and followed up until Jul. 1,2016. Clinical efficacy,the levels of T cell subsets (CD3+,CD4+,CD8+),survival time were ob-served in 2 groups. Single factor and multiple factor analysis was conducted for survival time. The occurrence of ADR was record-ed. RESULTS:The total response rate of observation group (32.39%) was higher than that of control group (25.00%),without statistical significance(P>0.05). Before treatment,there was no statistical significance in the levels of CD3+,CD4+ and CD8+ be-tween 2 groups(P>0.05). After treatment,the levels of CD3+ and CD4+ in observation group were increased significantly,while CD8+ level was decreased significantly;there was statistical significance compared to control group at corresponding period (P0.05). Single factor analysis showed that the survival time of patients aged 0.05). CONCLU-SIONS:Brucea javanica oil combined with gemcitabine and cisplatin in the treatment of advanced NSCLC patients,although not significantly improve the therapeutic effect,but can significantly improve the cellular immune function. With or without pleural effu-sion and age are infuential facters for survival time of advanced NSCLC patients.
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Bartter syndrome (BS) is a hereditary condition transmitted as an autosomal recessive (Bartter type 1 to 4) or dominant trait (Bartter type 5).The disease associates hypokalemic alkalosis with varying degrees of hypercalciuria.Here we presented a case (BS type Ⅱ) of a 17 years old female presented with polyhydramnios,polyuria,nephrocalcinosis and hypokalemia,which was alleviated after treatment with celecoxib and vitamin D3.DNA sequencing identified compound heterozygous KCNJ1 gene mutations,c.931 C > T (p.R311 W) and c.445-446insCCTGAACAC (p.V149Afs,150X),with the latter a novel mutation.Her father and mother were heterozygous carriers of c.931C > T (p.R311W) and c.445-446insCCTGAACAC (p.V149Afs,150X),respectively.In conclusion,this case of BS type 1 is caused by a novel compound heterozygous KCNJ1 mutation.Further studies are needed to verify the effect of celecoxib in BS patients.
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Bartter syndrome (BS) is a hereditary condition transmitted as an autosomal recessive (Bartter type 1 to 4) or dominant trait (Bartter type 5).The disease associates hypokalemic alkalosis with varying degrees of hypercalciuria.Here we presented a case (BS type Ⅱ) of a 17 years old female presented with polyhydramnios,polyuria,nephrocalcinosis and hypokalemia,which was alleviated after treatment with celecoxib and vitamin D3.DNA sequencing identified compound heterozygous KCNJ1 gene mutations,c.931 C > T (p.R311 W) and c.445-446insCCTGAACAC (p.V149Afs,150X),with the latter a novel mutation.Her father and mother were heterozygous carriers of c.931C > T (p.R311W) and c.445-446insCCTGAACAC (p.V149Afs,150X),respectively.In conclusion,this case of BS type 1 is caused by a novel compound heterozygous KCNJ1 mutation.Further studies are needed to verify the effect of celecoxib in BS patients.
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Objective To study the impact of human urinary kallidinogenase (HUK) on collateral circulation and blood perfusion in patients with acute cerebral ischemia (ACI) using multi-modality CT methods. Methods In a randomized controlled clinical trial, 75 patients diagnosed with ACI were enrolled and divided into experiment group (treated with HUK)and control group (untreated with HUK). All participants underwent computer technology perfusion (CTP) and computed tomographic angiography (CTA) examination before and fourteenth day after treatment. The CT cerebral perfusion imaging (CTP), CT cerebrovascular imaging (CTA) and National Institutes of Health Stroke Scale (NIHSS) score were analyzed in two groups. The NIHSS score, cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) were compared between the two groups before and after 14 days therapy. Results ① After treatment, The two group showed increased CBF and CBV values and decreased MTT and TTP values. The CBF improvement was significantly better in the HUK-treated group than in the control group (t=2.470,P<0.05).②MTT and TTP were shorter in the HUK-treated group than in the control group (t=2.126, t=2.213, P<0.05).③ CTA maximum intensity projection (MIP) sequence revealed that the number of patients collateral vessels was significantly increased in the HUK-treated group than in the control group ( x2=4.265, P<0.05). ④The NIHSS score improvement was significantly better in the HUK-treated group after 14 days treatment than in the control group (t=4.330, P<0.05). Conclusion Human urinary kallidinogenase can improve blood perfusion and ameliorates neurological deficits. It is a safe and effective drug for treating ACI patients. The multi-modality CT methods are effective measure to assess blood perfusion and collateral circulation in patients with acute cerebral ischemia.
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Objective To observe the influence of serum containing esculentoside A(EsA) on the proliferation of glomerular mesangial cell (GMC) and the activation of ERK1/2-AP-1 pathway of glomerular mesangial cell induced by IL-1β.Methods SD rats were gavaged by different doses of EsA(5,10,20,40 mg/kg) for getting medicated sera.The control group was set (gavage by 0.5sodium carboxymethylcellulose);the EsA medicated serum was used to treat rGMC.The control serum group was set.The influence of EsA medicated serum in each group on rGMC proliferation was detected by MTT;the rGMC was divided into the blank control group,IL-1β single action group,IL-1β+ EsA double action group,IL-1β+ U016 double action group and IL-1β+ U0126 + EsA combined action group,which were synchronized and then cultured for 48 h.Western blot was used to detectthe expression of p-ERK1/2 and AP-1 an the imaging analysis was performed.Results The EsA medicated serum(5-10 mg/kg gavage) inhibited the cellular proliferation(P<0.05 or P<0.01);the IL-1β group promoted the expression of p-ERK1/2 and AP-1 in rGMC(P< 0.05),after acting on rGMC in the IL-1β+EsA double action group,IL-1β+U0126 double action group and IL-1β+U0126+EsA combined action group,the expression of p-ERK1/2 and AP-1 was decreased(P<0.05).Conclusion Serum containing EsA (5~10 mg/kg gavage) significantly inhibits the rGMC proliferation;EsA inhibits IL-1β induced rGMC proliferation,its action pathway on ERK1/2-AP-1 is one of mechanisms for inhibiting rGMC proliferation.
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Acute nonvariceal upper gastrointestinal bleeding (ANVUGIB)is a commonly seen gastrointestinal emergency.Rockall and Blatchford scoring system are commonly used for risk stratification in ANVUGIB.Aims:To investigate the predictive values of Rockall and Blatchford scoring system for assessing the risk of blood transfusion,surgical intervention and mortality in patients with ANVUGIB.Methods:Five hundred and ninety hospitalized patients with ANVUGIB were scored by Rockall and Blatchford scoring system,respectively.Predictive values of these two scoring systems for assessing the risk of blood transfusion,surgical intervention and mortality were assessed by area under the receiver operating characteristic (ROC)curve (AUC).Results:Rockall and Blatchford scores in patients with blood transfusion,surgical intervention and died were significantly higher than those in patients without blood transfusion,surgical intervention and survived (P <0.01 ).The AUC of Rockall scoring system for predicting blood transfusion,surgical intervention and mortality were 0.785 (95% CI:0.743-0.828,P=0.000),0.765 (95% CI:0.693-0.837,P=0.000),0.835 (95% CI:0.703-0.966,P=0.005),respectively.The AUC of Blatchford scoring system for predicting blood transfusion,surgical intervention and mortality were 0.812 (95%CI:0.775-0.848,P=0.000),0.870 (95%CI:0.811-0.930,P=0.000),0.784 (95% CI:0.614-0.954,P=0.017),respectively.Conclusions:Rockall and Blatchford scoring system have high predictive value for blood transfusion,surgical intervention and mortality in patients with ANVUGIB.Rockall scoring system is better for predicting mortality,while Blatchford scoring system is better for predicting blood transfusion and surgical intervention.
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Dendritic cells (DCs)can capture HIV from the mucosal site and carry it to the draining lymph nodes to promote CD4 + T cell infection.DC-SIGN(CD209)plays a vital role during this process. Heroin,methamphetamine and cocaine are the most abused drugs used by drug abusers,which can increase the opportunities of HIV infection.Drugs acting on the corresponding receptors activate the downstream signaling pathway and regulate the expression of DC-SIGN on the surface of DCs,weakening the inhibited effects of immune cells on HIV and promoting HIV infection in many aspects.Given the multiplex effects of drugs on immune function,this article reviews the relationship between abused drugs,DCs and HIV infection,particularly in the signal pathway on immune modulation.
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Objective To observe the therapeutic effect of Shenqi Fuzheng injection combined with EP chemotherapy in the treatment of non small cell lung cancer (NSCLC),and to improve the quality of life and side effects.Methods 60 cases of NSCLC were randomly divided into observation group and control group,30 cases in each group.The two groups were treated with EP,the observation group was treated with Shenqi Fuzheng injection for two courses.The life quality and adverse effects were observed.Results The quality of life of the two groups after treatment was compared,the difference was statistically significant (93.3% vs 70.0%,χ2 =2.83,P <0.05),the quality of life in the observation group was significantly higher than that in the control group.The white blood cell reduction,anemia and liver and kidney function damage between the two groups had statistically significant differences (P =0.011,0.025,0.016),the adverse reaction of the observation group was less than the control group.Conclusion Shenqi Fuzheng injection combined with EP regimen in the treatment of NSCLC can protect bone marrow hematopoietic function and improve the quality of life of patients with NSCLC chemotherapy.It can be used as one mean of Chinese and western treatment for patients with NSCLC in clinical application.
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Objective To study the relieving cough and reducing phlegm effects and acute toxicity of the Kujyukekuan mixtures. Methods The method used in our study is a cough model induced by the ammonia water , the phenol red test in mice, the mouse pinna swelling model induced by xylene and the maximum tolerant dose experiment. Results In antitussive experiments, R value of Kujyukekuan mixtures at low, medium and high dose of was 112. 26%, 143. 29%, 162. 07%, respectively regarding as ineffective, effective and marked effective;Kujyukekuan mixtures at medium and high doses increased the excretion of phenolsulfonphthalein in the trachea of mice (compared with the normal control group, P<0. 05 or P<0. 01),the results showed good concentration-response relationship;Kujyukekuan mixtures at low, medium and high dose significantly reduced mouse auricle swelling caused by xylene (compared with normal control group, P<0. 01), the results presented a good concentration-response relationship;the MTD of Kujyukekuan mixture was 326. 76 g·kg-1. Conclusion Kujyukekuan mixtures at medium and high doses exert significant eliminating cough and phlegm effects and strong anti-inflammatory property, and has a good security.