In this paper, further study was made on the teratogenicity and the morphological teratogenesis mechanism of neural tube defects (NTD) caused by cyclophosphamide(CP). Pregnant SD rats were given single intraperitoneal injection of CP 15 mg/kg on day 13 of gestation. The fetuses were removed on day 20 of gestation, weighed and examined for external malformations. Some embryos were removed respectively at 4, 8, 12, 24, 48 hr after administration of CP, and examined with light microscope and electron microscope. The results showed that CP has obvious embryotoxie and teratogenic effects. Of the survivings, 97.46％ showed external malformations including encephalocele, exencephaly, opened eyes, micrognathia, limb and digital defects etc. We considered that the possible way by which CP caused the malformation on developing embryos may involve the following aspects: (1) CP caused DNA-synthesising cells to degenerate and become necrosis. (2) The cellular organelle (mitochondria and endoplasmic reticulum, etc.) became irregular in shape and fragmented. (3) The mesenchyme surrounding the neural tube were also damaged by CP and therefore influenced the skull ossification.

Objective To investigate the expressions of guanylyl cyclase-c(GC-C) and caudal-type homeobox transcription factor 2 (CDX2) in human gastric tissues and precursor lesions and its significance. Methods The cancerous and paracancerous (5 cm from cancer lesion )samples from 30 cases of gastric cancer and 32 samples including 23 intestinal metaplasia and 9 dysplasia were collected. The mRNA expressions of GC-C and CDX-2 were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and proteins of GC-C and CDX-2 were measured by using Western blot and immunofluorescence methods. Results The mRNA expressions of GC-C and CDX-2 were absent in paracancerous tissues, but were 66.7% and 63.3% in cancerous tissues, respectively(P=0. 000). The Western blot indicated that expressions of GC-C and CDX-2 were 19/30 and 17/30 in cancerous tissues, but absent in paracancerous tissues(P=0. 000). The immunofluorescence examination revealed that GC-C and CDX-2 expressions were 39.1% and 39.1% in intestinal metaplasia, 55.6% and 55.6% in dysplasia, and 56.7% and 60.0% in cancerous tissues, respectively, but absent in paracancerous tissues. Moreover, expressions of GC-C and CDX-2 showed a statistical difference between intestinal-type and diffuse-type of gastric cancer (P＜ 0.05) ,but had no correlation with age, sex, size of the lesion, clinical stage and lymphnode metastasis. The positive correlation was found in expressions of GC-C and CDX2 between intestinal metaplasia and cancerous tissues(r=0. 4524 and 0. 3845, P= 0. 037 and 0. 0408, respectively). Conclusions The over expressions of GC-C and CDX2 in human gastric cancer is associated with precursor lesions and may play an important role in the carcinogenesis of gastric cancer. The examination of GC-C and CDX2 expressions will be helpful in diagnosing gastric cancer and precursor lesions.

Objective To detect mutations of the ABCA12 gene in 2 Chinese families with autosomal recessive congenital ichthyosis (ARCI).Methods According to the typical clinical manifestations,two probands were diagnosed with ARCI.DNA was extracted from the peripheral blood samples collected from the patients and their parents.High-throughput sequencing was conducted by using multi-gene array for genetic skin disorders to determine mutation sites in the probands,and then DNA isolated from the probands and their parents were bidirectionally verified by Sanger sequencing.Results Two compound heterozygous mutations (c.2759A＞G and c.7004A＞G) in the ABCA12 gene were found in the proband 1,and another two compound heterozygous mutations (c.6163_6164insT and c.7406G＞A) were identified in the proband 2.The parents of the two probands were heterozygous carriers of one of the two mutations in the ABCA12 gene.Function prediction for the 4 mutations showed that all of the 3 missense mutations (c.2759A＞G,c.7004A＞G and c.7406G＞A) may exert pathogenic effect,and fragnin encoded by the frameshift mutation c.6163_6164insT may also affect protein function,c.2759A＞G and c.6163_6164insT were newly identified mutation sites.Conclusion The compound heterozygous mutations in the ABCA 12 gene are the causative mutations responsible for ARCI in the two probands of the two pedigrees.

To prepare recombinant fox growth hormone (fGH), we amplified its cDNA from silver fox pituitary tissue by RT-PCR and cloned into yeast shuttle vector pPIC9K down stream of a-factor signal peptide sequence by SnaB I and Not I restriction sites. The recombinant secretion vector pPIC9K/fGH, linearized by Sal I, was transformed into histidine-deficient Pichia pastoris strain GS115 by electroporation. We selected His+ -transformed methylotropic (His+, Mut+) yeast using histidine-absent medium containing dextrose (MD) or methanol (MM) as the only carbon source, and then screened the recombinant GS115 with multi-copy fGH genes by G418. The secretive expression of fGH was performed under the induction of methanol in shaking flask culture. The results showed that the fGH cDNA sequence amplified in this paper was basically in consistence with the published in GenBank. We achieved the secretive expression of recombinant fGH identified by SDS-PAGE and Western blotting. The fGH expression level was 119 mg/L, accounted for 34% of total proteins in fermentation medium.
Animals ; Base Sequence ; Cloning, Molecular ; DNA, Complementary ; genetics ; Electroporation ; Foxes ; genetics ; Genetic Vectors ; genetics ; Growth Hormone ; biosynthesis ; genetics ; Molecular Sequence Data ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics

Objective: To explore the relative importance of different food attributes and levels in food decision making of school aged children, and to understand their meal preferences, so as to provide the evidence for formulating precise intervention strategies for dietary behaviours of school aged children. Methods: From May to June 2024, a total of 854 children aged 11 to 15 years old were selected from 2 middle schools (each school in urban and rural areas) in both Hubei Province and Anhui Province by stratified cluster random sampling method to conduct a D-optimal discrete choice experiment. The mixed Logit model was used to analyze children s preference for meal attributes and different levels, and to calculate the relative importance (RI) of attributes and willingness to pay (WTP) in meal choices. Results: The included five food attributes had statistical significance on meal choice of school aged children ( P <0.05). The relative importance of food attributes affecting the meal choices of school aged children in descending order were dining mode ( RI =31.26%), food varieties ( RI =30.56%), cooking method( RI =23.84%), taste( RI =8.06%) and price ( RI =6.27%). Among them, school aged children preferred home cooked meals ( β =0.74) (WTP=86.3 yuan),varied foods(grain/tubers+vegetables+fish, meat, eggs and beans) ( β =0.61) (WTP=71.9 yuan), fried/roasted cooking ( β =0.51) and spicy taste ( β =0.33).Price was negatively correlated with meal choices( β =-0.01) ( P <0.05). Based on residential area and body mass index (BMI), the stratified analysis showed that dining mode was highest in the relative importance for rural children with overweight and obese children ( RI =31.28%,34.17%), both of whom preferred home cooked meals ( β =0.76, 0.91), and meals containing fish, meat, eggs and beans with grain/tubers or grain/tubers and vegetables in terms of food choice (area: β =0.53, 0.53 ; BMI: β =0.55, 0.56) ( P <0.05). Conclusions School aged children have different preferences for different attributes of meals. The quality of school meals should be improved,the cost of buying healthy meals should be reduced,targeted family health education should be carried out,and healthy cooking methods should be advocated.

Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)significantly improve the survival of advanced lung adenocarcinoma patients harboring EGFR mutation.Limited to the standards of tumor tissue samples and detection methods,still some people can't receive target therapy following genetic guidance.This study was to explore the relevance between serum tumor markers and treatment of EGFR-TKIs.Methods We retrospectively collected the clinical information of advanced lung adenocarcinoma patients harboring EGFR mutation,who received EGFR-TKIs as first-line therapy from June 2009 to June 2014 in Peking University Cancer Hospital,analyzed the relationship between serum tumor markers and efficacy of EGFR-TKIs.Results The objective response rate (ORR)was 52.8％ and the disease control rate (DCR) was 89.3％.The results showed that,patients with high CEA level before treatment responded better to TKIs (ORR 61.3％ vs 35.9％,DCR 95.2％ vs 74.4％,P＜0.001).Similar phenomena was found in patients with CEA decreased 1 month later (61.5％ vs 25％,P=0.002).Progression-free survival (PFS) significantly prolonged in patients with elevated baseline CEA (mPFS 9.8 mo vs 5.9 mo,P=0.027).To the opposite,PFS was significantly shorter in patients with elevated baseline CYFRA21-1 and CA125 (mPFS 9.0 mo vs 11.4 mo,P=0.029;9.0 mo vs 11.5 mo,P=0.023,respectively).Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score of 0-1,normal baseline CYFRA21-1 and CEA decline predicted longer PFS.The overall survival (OS) was highly associated with elevated CYFRA21-1 and CA125 (median OS 25.1 mo vs 52.5 mo,P=0.003;22.7 mo vs 55.0 mo,P＜0.001,respectively),while independent of CEA.Conclusion High level of baseline CEA and decline 1 month after treatment could predict the efficacy of EGFR-TKIs in patients with advanced lung adenocarcinoma.While high levels of baseline CYFRA21-1 and CA125 indicated shortened survival.

BACKGROUND: Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China. METHODS: This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs . ≥100,000 copies/mL) and CD4 + cell count (<200 vs . ≥200 cell/µL). Median time to TND VL was assessed by Kaplan-Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs). RESULTS: We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain. CONCLUSIONS In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.
Adult ; Humans ; Anti-HIV Agents/therapeutic use* ; China ; Emtricitabine/pharmacology* ; HIV Infections/drug therapy* ; HIV-1 ; Lamivudine/pharmacology* ; Lipids ; Retrospective Studies