Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.180
Filter
1.
Acta Pharmaceutica Sinica ; (12): 424-431, 2024.
Article in Chinese | WPRIM | ID: wpr-1016645

ABSTRACT

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL-1 and 9-150 ng·mL-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L-1 ammonium formate (D), with a flow rate of 0.2 mL·min-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI+), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL-1, 3-100 ng·mL-1 and 0.9-30 ng·mL-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

2.
Shanghai Journal of Preventive Medicine ; (12): 150-156, 2024.
Article in Chinese | WPRIM | ID: wpr-1016543

ABSTRACT

ObjectiveTo investigate the detection rate and main influencing factors of growth retardation in infants aged 0-3 in Minhang District, and to provide relevant evidence for early intervention, nutrition promotion and health guidance in the future. MethodsFrom September 1, 2020 to August 31, 2021, the height, weight, basic information of parents, feeding methods, and lifestyle habits of infants who received systematic healthcare aged 0‒3 in community health service centers and Minhang maternal child health hospital were collected, and the current situation and influencing factors of infant growth retardation were analyzed. ResultsAmong the 68 637 infants who underwent a systematic physical examination in Minhang District, the total detection rate of growth retardation was 5.03% (3 453/68 637). The detection rates in the 0-year-old, 1-year-old, 2-year-old, and 3-year-old groups were 6.57% (1 636/24 885), 3.90% (664/17 031), 4.62% (827/17 905), and 3.72% (326/8 773), respectively. There was no difference in the detection rate of growth retardation between boys and girls (P>0.05), and a multinomial logistic regression analysis of 13 influencing factors (infant birth weight, birth length, parental weight, height, education level, mother’s childbearing age, delivery mode, household registration, feeding mode within 6 months, infant sleep, etc.) in univariate analysis showed that birth weight <2 500 g (OR=3.99, 95%CI: 2.809‒5.674) or ≥4 000 g (OR=12.78, 95%CI: 8.868‒18.443), maternal height <150 cm (OR=7.10, 95%CI: 4.294‒11.753), paternal height <160 cm (OR=5.65, 95%CI: 2.792‒11.422), maternal education level of junior high school and below (OR=1.31, 95%CI: 1.087‒1.588), paternal education level of junior high school and below (OR=1.02, 95%CI: 0.838‒1.236), mixed feeding (OR=1.15, 95%CI: 1.031‒1.288), and sleep duration exceeding the recommended time (OR=1.58, 95%CI: 1.466‒1.710) were risk factors for growth retardation in infants aged 0‒3. Infants with a birth length <50 cm or with household registration in Shanghai had a higher incidence of growth retardation. ConclusionGrowth retardation in infants aged 0‒3 is influenced by a combination of genetic, environmental, and sleep factors. It is essential for parents to realize the impact of growth retardation on the future of their children early on and actively participate in the early detection, screening, and intervention of growth retardation.

3.
Shanghai Journal of Preventive Medicine ; (12): 143-149, 2024.
Article in Chinese | WPRIM | ID: wpr-1016542

ABSTRACT

ObjectiveTo investigate the changes in the pathogen spectrum of viral diarrhea in local pediatric inpatients as well as any variations in genotypes of major pathogens during the COVID-19 control period. MethodsFecal samples were collected from the children <5 years who were hospitalized due to acute gastroenteritis in a pediatric hospital in Shanghai. PCR test was carried out to detect rotavirus, norovirus, sapovirus, astrovirus and enteric adenovirus, and then genotyping was performed for major pathogens. ResultsOut of 546 samples, 37.55% tested positive for virus with the following positive rate ranking: norovirus GⅡ (22.16%), group A rotavirus (16.12%), astrovirus (2.93%), enteric adenovirus (2.38%), sapovirus (0.92%) and norovirus GⅠ (0.18%). The predominant genotype within norovirus GⅡ were GⅡ.4[P31] and GⅡ.4[P16] with a proportion of 24.79% and 14.05% respectively. The detection rate of GⅡ.4[P31] dropped significantly over the 2-year period (χ2=16.140,P<0.001). In addition, an emerging rotavirus genotype G8P [8], which was rarely found nationally, was discovered for the first time locally with an increasing proportion, accounting for 7.95% of all rotavirus positive cases. Phylogenic analysis demonstrated that the representative strains of this genotype were genetically closer to the DS-1-like G8P [8] strain found in Southeast Asia. ConclusionThe changes in the prevalence of various norovirus genotypes together with the emergence of rare rotavirus genotype in the local area illustrate the importance of continuous monitoring of viral diarrhea and genotyping of key pathogens. Increased local activity of the rare genotype also adds new parameters in the efficacy evaluation of marketed vaccines and development of potential new vaccines in near future.

4.
Chinese Medical Ethics ; (6): 601-606, 2024.
Article in Chinese | WPRIM | ID: wpr-1012948

ABSTRACT

In order to explore the ethical review experience of organ donation and transplantation after the death of citizens, and provide reference value for medical institutions to carry out corresponding ethical review. By using descriptive research, purpose sampling method and the principle of data saturation, 10 members and secretaries of ethics committee on clinical application of organ transplantation technology were finally selected as respondents for semi-structured interviews. The Colaizzi 7-step analysis method was adopted to analyze, summarize and refine the theme. The results showed that the ethical review experience of organ donation and transplantation after the death of citizens included four themes: the responsibilities of ethics committee, the key points of ethics review, the form of ethics review conference and its advantages and disadvantages, and the construction of the ethics committee of organ transplantation. Therefore, there are defects in the ethical review of organ donation and transplantation in medical institutions at present. These can be remedied by enriching elements of the ethical review following the four principles of medical ethics, refining the laws related to organ donation after citizens’ death, constructing a reasonable and efficient pattern of ethical review conference, and establishing a robust and appropriate operation mode of organ transplantation ethics committee.

5.
Journal of Clinical Otorhinolaryngology Head and Neck Surgery ; (12): 44-49, 2024.
Article in Chinese | WPRIM | ID: wpr-1011100

ABSTRACT

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome(AS) patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33(25 males, 8 females, aged 3.4-27.8 years) were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease(ESRD), predominantly males (6/7). The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group(P=0.013). There was no correlation between the progression of renal disease and long-term hearing level(P>0.05). kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss(P=0.048), and there was no correlation with the severity of hearing loss(P>0.05). Among 11 cases, theCOL4A5mutationwas most common (8 out of 11), but there was no significant correlation between the mutation type and hearing phenotype(P>0.05). Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.


Subject(s)
Male , Child , Female , Humans , Nephritis, Hereditary/pathology , Retrospective Studies , Kidney , Deafness , Hearing Loss/genetics , Kidney Failure, Chronic/pathology , Mutation
6.
Biomedical and Environmental Sciences ; (12): 42-53, 2024.
Article in English | WPRIM | ID: wpr-1007907

ABSTRACT

OBJECTIVE@#This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.@*METHODS@#A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.@*RESULTS@#Six potential active components, namely quercetin, β-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment.@*CONCLUSION@#Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.


Subject(s)
Humans , Quercetin/therapeutic use , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Drugs, Chinese Herbal , Fatigue/drug therapy
7.
Journal of Clinical Hepatology ; (12): 319-326, 2024.
Article in Chinese | WPRIM | ID: wpr-1007247

ABSTRACT

ObjectiveTo investigate the role and mechanism of DNA repair regulation in the process of hepatocellular carcinoma (HCC) recurrence. MethodsHCC tissue samples were collected from the patients with recurrence within two years or the patients with a good prognosis after 5 years, and the Tandem Mass Tag-labeled quantification proteomic study was used to analyze the differentially expressed proteins enriched in the four pathways of DNA replication, mismatch repair, base excision repair, and nucleotide excision repair, and the regulatory pathways and targets that play a key role in the process of HCC recurrence were analyzed to predict the possible regulatory mechanisms. The independent samples t-test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsFor the eukaryotic replication complex pathway, there were significant reductions in the protein expression levels of MCM2 (P=0.018), MCM3 (P=0.047), MCM4 (P=0.014), MCM5 (P=0.008), MCM6 (P=0.006), MCM7 (P=0.007), PCNA (P=0.019), RFC4 (P=0.002), RFC5 (P<0.001), and LIG1 (P=0.042); for the nucleotide excision repair pathway, there were significant reductions in the protein expression levels of PCNA (P=0.019), RFC4 (P=0.002), RFC5 (P<0.001), and LIG1 (P=0.042); for the base excision repair pathway, there were significant reductions in the protein expression levels of PCNA (P=0.019) and LIG1 (P=0.042) in the HCC recurrence group; for the mismatch repair pathway, there were significant reductions in the protein expression levels of MSH2 (P=0.026), MSH6 (P=0.006), RFC4 (P=0.002), RFC5 (P<0.001), PCNA (P=0.019), and LIG1 (P=0.042) in recurrent HCC tissue. The differentially expressed proteins were involved in the important components of MCM complex, DNA polymerase complex, ligase LIG1, long patch base shear repair complex (long patch BER), and DNA mismatch repair protein complex. The clinical sample validation analysis of important differentially expressed proteins regulated by DNA repair showed that except for MCM6 with a trend of reduction, the recurrence group also had significant reductions in the relative protein expression levels of MCM5 (P=0.008), MCM7 (P=0.007), RCF4 (P=0.002), RCF5 (P<0.001), and MSH6 (P=0.006). ConclusionThere are significant reductions or deletions of multiple complex protein components in the process of DNA repair during HCC recurrence.

8.
Chinese Pharmacological Bulletin ; (12): 1718-1724, 2023.
Article in Chinese | WPRIM | ID: wpr-1013705

ABSTRACT

Aim To investigate the role of autophagy in the dysfunction of testicular TM4 cell junction induced by ERα down-regulation. Methods TM4 cells were treated with different concentrations of E R a inhibitor ICI182780 (ICI), and the proliferative activity of TM4 cells was detected by CCK-8 method. The number and morphological changes of TM4 cells were observed by light microscope. The levels of E R a, junction function related proteins and autophagy marker proteins were detected by Western blot. The expression and localization of Cx43 were detected by immunofluorescence staining. The cells were treated with chloroquine (CQ) and ICI for 24 h. The expression levels of autophagy and junction function related proteins were detected by Western blot. Results When ICI concentration was 50 nmol • L ~ or above, the cell viability decreased significantly. The increase of cell vacuoles in ICI group was observed by light microscope. Compared with normal control group, the protein expression levels of E R a, ZO-1, occludin, claudin-11, p-catenin and Cx43 in ICI groups significantly dropped, while the expression levels of N-cadherin and E-cadherin had no significant changes; LC3 II significantly rose, while p62 expression significantly fell. The results of immunofluorescence showed that the fluorescence expression of Cx43 in ICI group decreased significantly, but the position of CX43 did not change significantly. Compared with ICI group, the expression levels of LC3 II, p62, Cx43, ZO-1 and β-Catenin significantly increased. Conclusions The down-regulation of E R a leads to damage of TM4 cell junction function, which may be related to the activation of autophagy.

9.
Chinese Pharmacological Bulletin ; (12): 2346-2353, 2023.
Article in Chinese | WPRIM | ID: wpr-1013677

ABSTRACT

Aim To study the effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress. Methods C57BL/6J male mice were assigned into normal group and high-fat diet group randomly, with six mice in each group. The mice in normal group or high-fat diet group were fed with regular or high-fat diet continuously for five months. The mice were weighed, anesthetized, and euthanized to collect testicular and epididymal tissue for analysis. The testicular tissue was weighed and their indices were calculated. Epididymal tissue was collected for semen analysis. The morphological alterations of testicular tissue were observed using hematoxylin-eosin ( HE ) staining. The apoptosis of germ cells was detected by TUNEL staining and the apoptotic indices were calculated. The expression levels of apoptosis and endoplasmic reticulum stress-related proteins in testicular tissue were detected by Western blot. The protein expression and localization of GRP78 in testicular tissue were further detected by immunofluorescence. Results The results showed that compared to the normal group, the high-fat diet group had a significant increase in body weight, a significant decrease in testicular index, sperm concentration, and sperm vability, loose arrangement of germ cells, significant thinning of the seminiferous epithelium, no significant change in the diameter of seminiferous tubules, a significant increase in germ cell apoptosis , with an increased apoptosis index, and significant increase in expression of Bax and cleaved-caspase-12,and a significant decrease in Bcl-2 protein expression. The expression levels of GRP78 , p-IREl, XBP1, and ATF6a proteins were significantly up-regulated, while p-PERK, p-eIF2a, ATF4 protein expression showed no significant changes. Immunofluorescence results further showed a significant increase in the expression of GRP78 protein in the testicular tissue,with no significant changes in the expression location. Conclusions High-fat diet can induce the apoptosis of mouse testicular germ cells, and the mechanism may be related to the activation of endoplasmic reticulum stress IRE1 and ATF6 signaling pathway.

10.
Chinese Journal of Obstetrics and Gynecology ; (12): 650-657, 2023.
Article in Chinese | WPRIM | ID: wpr-1012273

ABSTRACT

Objective: To investigate the clinical effect and the influencing factors of ultrasound-indicated cerclage and history-indicated cerclage in singleton gestation. Methods: The clinical data of 272 singleton pregnant women with cervical incompetence who underwent McDonald cervical cerclage due to medical history indication (history-indicated group) or ultrasound indication (ultrasound-indicated group) in Peking University First Hospital from January 2010 to February 2021 were retrospectively analyzed. The general clinical data and maternal and fetal outcomes were compared between the history-indicated group (141 cases) and ultrasound-indicated group (131 cases). According to the gestational age at delivery, 272 pregnant women who underwent cervical cerclage were further divided into ≥34 weeks group (225 cases) and <34 weeks group (47 cases), and the influencing factors of preterm birth before 34 weeks of gestation were analyzed. Results: (1) The median gestational age at cerclage was 16.6 weeks in the history-indicated group and 23.4 weeks in the ultrasound-indicated group, and the median gestational age extension at delivery was 21.4 weeks and 14.7 weeks, respectively, with statistically significant differences between the two groups (all P<0.05). (2) The full-term birth rate was 76.6% (108/141) in the history-indicated group and 71.0% (93/131) in the ultrasound-indicated group, the live birth rate was 97.2% (137/141) and 97.7% (128/131), and the median birth weight of live birth was 3 155 g and 3 055 g, respectively. The differences were not statistically significant (all P>0.05). Among 272 pregnant women with cervical cerclage, 265 neonates survived (97.4%, 265/272). The gestational age of 7 pregnant women who did not have live birth was ≤25 weeks of gestation (range: 19+1-25 weeks), and they were all clinically infected or confirmed chorioamnionitis or pathogenic microorganisms carrying during pregnancy, and their families gave up. The minimum birth weight of the surviving neonate was 850 g (gestational week of delivery was 26+6 weeks). (3) Univariate analysis showed that compared with ≥34 weeks group, the body mass index (BMI) of pregnant women in <34 weeks group was higher at 6-7 weeks of gestation (median: 24.5 vs 25.4 kg/m2), shorter cervical length (CL) at 1-2 weeks after surgery [(31.1±8.4) vs (26.1±11.0) mm], shorter CL at 26-28 weeks of gestation after surgery (median: 26.3 vs 16.0 mm), and higher incidence of elevated C-reactive protein (CRP) before and after surgery and before delivery. The differences were all statistically significant (all P<0.05). Multivariate logistic regression analysis showed that preterm birth before 34 weeks was negatively associated with CL at 26-28 weeks of gestation after cerclage (OR=0.902, 95%CI: 0.858-0.947; P<0.001), and was positively correlated with elevated CRP before delivery (OR=3.492, 95%CI: 1.652-7.381; P=0.001). There were no significant correlations between preterm birth and preoperative or postoperative CRP elevation, CL at 1-2 weeks after surgery, and BMI at 6-7 weeks of gestation (all P>0.05). Conclusions: Cervical cerclage for singleton pregnant women with cervical incompetence indicated by history or ultrasound both have good clinical efficacy, and there is no significant difference in maternal and fetal outcomes between the two groups. CL at 26-28 weeks of gestation and CRP before delivery are risk factors for preterm birth before 34 weeks of gestation after cervical cerclage.


Subject(s)
Infant, Newborn , Pregnancy , Humans , Female , Infant , Birth Weight , Premature Birth/prevention & control , Retrospective Studies , Ultrasonography , Cerclage, Cervical
11.
Chinese Journal of Hematology ; (12): 906-910, 2023.
Article in Chinese | WPRIM | ID: wpr-1012255

ABSTRACT

Objective: To compare digital polymerase chain reaction (dPCR) and real-time quantitative PCR (qPCR) measurements of BCR::ABL (P210) mRNA expression in patients with chronic myeloid leukemia (CML) . Methods: In this non-interventional, cross-sectional study, BCR::ABL (P210) mRNA was simultaneously measured by dPCR and qPCR in peripheral blood samples collected from patients with CML who underwent tyrosine kinase inhibitor therapy and who achieved at least a complete cytogenetic response from September 2021 to February 2023 at Peking University People's Hospital. The difference, correlation, and agreement between the two methods were evaluated using the Wilcoxon signed-rank test, Spearman's correlation, and Bland-Altman analysis, respectively. Results: In total, 459 data pairs for BCR::ABL mRNA expression measured by dPCR and qPCR from 356 patients with CML were analyzed. There was a significant difference in BCR::ABL mRNA expression between the two methods (P<0.001). When analyzed by the depth of the molecular response (MR), a significant difference only existed for patients with ≥MR4.5 (P<0.001). No significant difference was observed for those who did not achieve a major MR (no MMR; P=0.922) or for those who achieved a major MR (MMR; P=0.723) or MR4 (P=0.099). There was a moderate correlation between the BCR::ABL mRNA expression between the two methods (r=0.761, P<0.001). However, the correlation gradually weakened or disappeared as the depth of the MR increased (no MMR: r=0.929, P<0.001; MMR: r=0.815, P<0.001; MR4: r=0.408, P<0.001; MR4.5: r=0.176, P=0.176). In addition, the agreement in BCR::ABL mRNA expression between the two methods in those with MR4.5 was weaker than other groups (no MMR: ▉= 0.042, P=0.846; MMR:▉=0.054, P=0.229; MR4:▉=-0.020, P=0.399; MR4.5:▉=-0.219, P<0.001) . Conclusions: dPCR is more accurate than qPCR for measuring BCR::ABL (P210) mRNA expression in patients with CML who achieve a stable deep MR.


Subject(s)
Humans , Cross-Sectional Studies , Cytogenetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Real-Time Polymerase Chain Reaction , RNA, Messenger/genetics
12.
Acta Pharmaceutica Sinica B ; (6): 3321-3338, 2023.
Article in English | WPRIM | ID: wpr-1011132

ABSTRACT

Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide. Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs. Nevertheless, the adaptive immune responses of subunit vaccines are still unfavorable, which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design. An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy. In this review, we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration. The engineered subunit vaccines with lymph node and specific cell targeting ability, antigen cross-presentation, T cell activation properties, and tailorable antigen release patterns may achieve effective immune protection with high precision, efficiency, and stability. We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.

13.
Chinese Journal of Biotechnology ; (12): 4098-4107, 2023.
Article in Chinese | WPRIM | ID: wpr-1008014

ABSTRACT

Human induced pluripotent stem cells (hiPSCs) are promising in regenerative medicine. However, the pluripotent stem cells (PSCs) may form clumps of cancerous tissue, which is a major safety concern in PSCs therapies. Rapamycin is a safe and widely used immunosuppressive pharmaceutical that acts through heterodimerization of the FKBP12 and FRB fragment. Here, we aimed to insert a rapamycin inducible caspase 9 (riC9) gene in a safe harbor AAVS1 site to safeguard hiPSCs therapy by drug induced homodimerization. The donor vector containing an EF1α promoter, a FRB-FKBP-Caspase 9 (CARD domain) fusion protein and a puromycin resistant gene was constructed and co-transfected with sgRNA/Cas9 vector into hiPSCs. After one to two weeks screening with puromycin, single clones were collected for genotype and phenotype analysis. Finally, rapamycin was used to induce the homodimerization of caspase 9 to activate the apoptosis of the engineered cells. After transfection of hiPSCs followed by puromycin screening, five cell clones were collected. Genome amplification and sequencing showed that the donor DNA has been precisely knocked out at the endogenous AAVS1 site. The engineered hiPSCs showed normal pluripotency and proliferative capacity. Rapamycin induced caspase 9 activation, which led to the apoptosis of all engineered hiPSCs and its differentiated cells with different sensitivity to drugs. In conclusion, we generated a rapamycin-controllable hiPSCs survival by homodimerization of caspase 9 to turn on cell apoptosis. It provides a new strategy to guarantee the safety of the hiPSCs therapy.


Subject(s)
Humans , Induced Pluripotent Stem Cells , Sirolimus/metabolism , Caspase 9/metabolism , RNA, Guide, CRISPR-Cas Systems , Pluripotent Stem Cells/metabolism , Cell Differentiation , Puromycin/metabolism
14.
Chinese Journal of Biotechnology ; (12): 3436-3450, 2023.
Article in Chinese | WPRIM | ID: wpr-1007968

ABSTRACT

Azo dyes are widely used in textile, paper and packing industries, and have become one of the research hot spots in dye wastewater treatment because of their carcinogenicity, teratogenic mutagenicity, stable structure and degradation difficulty. In this study, the biodecolorization of acid orange 7 (AO7), an azo dye, by different white rot fungi was investigated, and the effect of different conditions on the decolorization rate of the dye was analyzed. At the same time, the degradation liquor was analyzed and the phytotoxicity experiment was performed to deduce the possible degradation pathway of AO7 and assess the toxicity of its degradation products. The results showed that the decolorization rate reached 93.46% in 24 h at pH 4.5, 28 ℃ by Pleurotus eryngii and Trametes versicolor when AO7 concentration was 100 mg/L. The biodegradation pathway of AO7 was initiated by the cleavage of the azo bond of AO7, generating p-aminobenzenesulfonic acid and 1-amino-2-naphthol. Subsequently, the sulfonic acid group of p-aminobenzene sulfonic acid was removed to generate hydroquinone. Moreover, the 1-amino-2-naphthol was de-ringed to generate phthalic acid and p-hydroxybenzaldehyde, and then further degraded into benzoic acid. Finally, hydroquinone and benzoic acid may be further oxidized into other small molecules, carbon dioxide and water. Phytotoxicity experiment showed that the toxicity of AO7 could be reduced by P. eryngii and T. versicolor.


Subject(s)
Hydroquinones , Trametes , Azo Compounds , Benzoic Acid
15.
Chinese Medical Ethics ; (6): 156-159, 2023.
Article in Chinese | WPRIM | ID: wpr-1005525

ABSTRACT

Natural disasters and epidemics are intertwined, posing a great threat to national health and property security, and hindering economic development. Faced with the complex rescue environment, the contradiction between individual interests and collective interests may escalate, causing ethical dilemmas different from those encountered in conventional medicine. In the context of COVID-19 epidemic prevention and control, how to maximize the coordination of the conflict between individual interests and collective interests, minimize the losses caused by disasters, and maintain social stability is a new topic of ethical research. Based on the ethical principles of public management, this paper explored the ethical conflicts of public management faced by emergency disaster rescue, in the view of providing ethical theoretical support for dealing with the practical difficulties of emergency public health crisis, and promoting the development and progress of disaster medical rescue work.

16.
Chinese Medical Ethics ; (6): 102-107, 2023.
Article in Chinese | WPRIM | ID: wpr-1005489

ABSTRACT

Spirit of Great Physician, puts forward relevant requirements on the moral standards and humanistic qualities that doctors should possess. By tracing the formation background of Spirit of Great Physician, analyzing its rich ideological connotation, reflecting on the needs of contemporary society for medical ethics on the basis of the medical ethics standard of Spirit of Great Physician, combining the background of social development and medical reform in the new era, as well as the moral dilemma in the medical environment, this paper proposed that contemporary society should take the combination of the internal requirements of "moral self-discipline" and the external constraints of "moral heteronomy" as the new path of medical ethics construction. The purpose of this study was to provide theoretical reference for improving the construction system of contemporary medical ethics, enhancing the moral character of medical staff and building a good medical environment.

17.
Sichuan Mental Health ; (6): 562-569, 2023.
Article in Chinese | WPRIM | ID: wpr-1005294

ABSTRACT

BackgroundDepression, anxiety, impulse control disorders, insomnia are prevalent non-motor symptoms of Parkinson's disease, severely impairing the quality of life of patients. Cognitive behavioral therapy (CBT) is a common psychological intervention for various clinical psychological conditions, which can improve anxiety, insomnia and depression in patients with Parkinson's disease. However, the current research evidence on the effects of CBT in improving quality of life in patients with Parkinson's disease remains inconsistent. ObjectiveTo assess the effects of CBT on the quality of life among patients with Parkinson's disease, so as to provide references for the clinical application of CBT in this population. MethodsOn May 25, 2023, a systematic search was conducted across PubMed, PsycINFO, Embase, CNKI, Wanfang Database and VIP Database to identify randomized controlled trials investigating the impact of CBT on the quality of life in patients with Parkinson's disease. Literature screening, quality evaluation and data extraction were performed, focusing on variables related to quality of life, anxiety, and depression. Meta-analysis was performed using Stata 13.0 and RevMan 5.3. ResultsA total of 11 studies with 456 participants were included, comprising 241 in the CBT group and 215 in the control group. The CBT group exhibited significantly higher quality of life compared with the control group (SMD=0.47, 95% CI: 0.27~0.67, P<0.01). Anxiety and depression scores in CBT group were significantly lower than those in the control group (SMD=-0.63,95% CI:-0.84~-0.43, P<0.01; SMD=-0.83, 95% CI: -1.15~-0.51, P<0.01). Among the 11 studies, 6 studies delivered CBT remotely and 5 studies implemented CBT face-to-face. Meta-analysis results revealed that remote CBT group yielded significantly higher quality of life (SMD=0.43, 95% CI: 0.17~0.70, P<0.01), and lower anxiety and depression scores (SMD=-0.62, 95% CI: -0.91~-0.34, P<0.01; SMD=-0.78, 95% CI: -1.34~-0.21, P<0.01) compared with the control group. Similarly, face-to-face CBT group showed better outcomes than the control group in terms of quality of life, anxiety and depression (SMD=0.51, 95% CI: 0.22~0.81, P<0.01; SMD=-0.64, 95% CI: -0.93~-0.35, P<0.01; SMD=-0.90, 95% CI: -1.20~-0.60, P<0.01). ConclusionCBT may contribute to alleviating anxiety and depression levels of patients with Parkinson's disease, and improving their quality of life.{Funded by Shanghai 13th Five-Year Key Specialty Construction Project (number, shslczdzk04901); Nature Fund Project of Shanghai Science and Technology Commission (number, 22ZR1459300); Shanghai Municipal Health Commission Traditional Chinese Medical Science Non-drug Therapy Demonstration Center Project [number, ZY(2021-2023) -0204-03]}

18.
Chinese Medical Journal ; (24): 1278-1290, 2023.
Article in English | WPRIM | ID: wpr-980923

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by progressive lung fibrogenesis and histological features of usual interstitial pneumonia. IPF has a poor prognosis and presents a spectrum of disease courses ranging from slow evolving disease to rapid deterioration; thus, a differential diagnosis remains challenging. Several biomarkers have been identified to achieve a differential diagnosis; however, comprehensive reviews are lacking. This review summarizes over 100 biomarkers which can be divided into six categories according to their functions: differentially expressed biomarkers in the IPF compared to healthy controls; biomarkers distinguishing IPF from other types of interstitial lung disease; biomarkers differentiating acute exacerbation of IPF from stable disease; biomarkers predicting disease progression; biomarkers related to disease severity; and biomarkers related to treatment. Specimen used for the diagnosis of IPF included serum, bronchoalveolar lavage fluid, lung tissue, and sputum. IPF-specific biomarkers are of great clinical value for the differential diagnosis of IPF. Currently, the physiological measurements used to evaluate the occurrence of acute exacerbation, disease progression, and disease severity have limitations. Combining physiological measurements with biomarkers may increase the accuracy and sensitivity of diagnosis and disease evaluation of IPF. Most biomarkers described in this review are not routinely used in clinical practice. Future large-scale multicenter studies are required to design and validate suitable biomarker panels that have diagnostic utility for IPF.


Subject(s)
Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Biomarkers , Lung Diseases, Interstitial , Lung , Bronchoalveolar Lavage Fluid , Disease Progression , Prognosis
19.
Chinese Acupuncture & Moxibustion ; (12): 575-583, 2023.
Article in Chinese | WPRIM | ID: wpr-980762

ABSTRACT

OBJECTIVE@#To systematically review the efficacy of acupuncture for the treatment of tobacco withdrawal syndrome.@*METHODS@#The randomized controlled trials (RCTs) regarding acupuncture for treatment of tobacco withdrawal syndrome were searched in CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane, Medline and EMbase databases. The search period was from January 1st of 2011 to December 31st of 2021. After data extraction and bias risk assessment of the included literature, the Meta-analysis was performed using RevMan5.4.1 software.@*RESULTS@#Totally 23 RCTs were included, including 2 120 patients. The Meta-analysis results showed that compared with medication, acupuncture showed no significant difference at improving Fagerström test for nicotine dependence (FTND) score (MD=0.16, 95%CI: -0.08, 0.41), heaviness of smoking index (HSI) score (MD=0.11, 95%CI: -0.13, 0.36), Minnesota nicotine withdrawal scale (MNWS) score (MD=0.12, 95%CI: -0.11, 1.35), questionnaire of smoking urges (QSU) score (MD=-0.30, 95%CI: -2.78, 2.18), Hamilton depression scale (HAMD) score (MD=0.76, 95%CI: -1.54, 3.06), abstinence rate (RR=0.95, 95% CI: 0.82, 1.10) and effective rate (RR=1.01, 95%CI: 0.95, 1.07). Acupuncture was superior to sham acupuncture in reducing MNWS score (MD=-4.88, 95%CI: -5.21, -4.55, P<0.000 01). Acupuncture was superior to cognitive behavioral therapy in reducing FTND score (MD=-1.41, 95%CI: -1.74, -1.08), MNWS score (MD=-4.28, 95%CI: -5.31, -3.25) and increasing abstinence rate (RR=2.19, 95%CI: 1.39, 3.45, P<0.000 01, P<0.001).@*CONCLUSION@#Acupuncture could effectively improve tobacco withdrawal syndrome, increase abstinence rate and effective rate. Limited by the quantity and quality of the included studies, this conclusion needs to be verified by more studies.


Subject(s)
Humans , Nicotiana , Acupuncture Therapy , Syndrome , Nicotine , Smoking
20.
Journal of Environmental and Occupational Medicine ; (12): 823-829, 2023.
Article in Chinese | WPRIM | ID: wpr-979199

ABSTRACT

Background The incidence of Legionnaires' disease is increasing globally and artificial water environment is becoming a common source of outbreaks. Molecular typing techniques can help prevent and control Legionella. Objective To understand the molecular epidemiological characteristics of Legionella pneumophila in artificial water environment of Shanghai hospitals, and provide a scientific basis for the prevention and control of Legionnaires' disease. Methods Water samples were collected from artificial water environment in 14 hospitals from May to October each year from 2019 to 2020 in Shanghai. A total of 984 water samples were collected from 8 Grade-A tertiary hospitals and 6 non-Grade-A tertiary hospitals, including 312 samples of cooling water, 72 samples of chilled water, and 600 samples of tap water. The water samples were isolated and serotyped for Legionella pneumophila and preserved, and the positive rate of Legionella pneumophila in the samples was used as an indicator of contamination. The preserved strains were resuscitated and 81 surviving strains were obtained for pulsed field gel electrophoresis (PFGE) typing analysis. Results A total of 124 Legionella pneumophila positive water samples were detected, with a positive rate of 12.60%. The positive rate was higher in the Grade-A tertiary hospitals (16.54%, 87/526) than in the non-Grade-A tertiary hospitals (8.08%, 37/458) (χ2=15.91, P<0.001). The positive rate of cooling water (23.40%) was the highest among different types of water samples, and the difference was statistically significant (χ2=61.19, P<0.001). The difference in positive rate of tap water was statistically significant among different hospital departments (χ2=11.37, P<0.05). The positive rate in 2019 (15.06%) was higher than that in 2020 (9.84%) (χ2=6.23, P<0.05). From May to October, August had the highest annual average positive rate (16.46%) and October had the lowest (8.54%), but the difference in positive rates among months was not statistically significant (χ2=5.39, P=0.37). The difference in positive rate among districts was statistically significant (χ2=24.88, P<0.001). A total of 131 strains of Legionella pneumophila were isolated, with serotype 1 (80.15%, 105/131) predominating. Among the 81 surviving strains of Legionella pneumophila subjected to PFGE typing, the band-based similarity coefficients ranged from 41.30% to 100%. Among the 29 PFGE band types (S1-S29) recorded, each band type included 1-10 strains, and S28 was the dominant band type. Four clusters (I-IV) of PFGE band types were identified, accounting for 66.67% (54/81) of all strains and containing 13 band types. Conclusion Legionella pneumophila contamination is present in the artificial water environment of hospitals in Shanghai from 2019 to 2020, and the contamination in tap water deserves attention. The detected serotype of Legionella pneumophila is predominantly type 1, and PFGE typing reveals the presence of genetic polymorphism. Therefore, the monitoring and control of Legionella pneumophila in hospital artificial water environment should be strengthened.

SELECTION OF CITATIONS
SEARCH DETAIL