Objective:This study aims to evaluate the clinical effect and adverse reactions of oxaliplatin or irinotecan plus capecitabine treatment for colorectal liver metastases. Methods:Data from 125 cases of colorectal liver metastasis patients were continuously enrolled and randomized into two groups, i.e., 63 in group one (treatment group) and the other 62 in group two (the control group). Capecitabine was administered at 1 000 mg/m2 doses, twice a day from d1 to d14, to all patients. Irinotecan was administered at 150 mg/m2 in d1 to group one, and oxaliplatin was administered at 130 mg/m2 in d1 to group two. The drug administration cycle lasted for 21 days in both regimens, with at least 6 administration cycles. The total course was for 6 months at most. The therapeutic efficacy, median progression-free survival time, median survival time, short-term clinical effect, and adverse drug reaction were monthly determined. Results:The overall response rates and disease control rates were 33.3%and 66.7%in group one, respectively, and 35.5%and 70.9%in group two, respectively, with no significant differences between the groups (P>0.05). The median survival time and median progression-free survival time were 14 months and 5 months in group one, respectively, and 12 months and 5 months in group two, with no significant differences between the two groups (P>0.05). The level-Ⅲand-Ⅳadverse drug reactions mainly include hematological toxicity, gastrointestinal reactions, and hand-foot syndrome. The diarrhea frequency is obviously higher in group one than in group two, and the difference between the two groups is sta-tistically significant (P<0.05). No significant differences were observed in the other adverse reactions between the groups (P>0.05). Conclusion:The Oxaliplatin or Irinotecan plus Capecitabine treatment is effective for colorectal liver metastases, which enhances survival rate and reduces patient suffering because of it has less side effects and good tolerance. The treatment must be further generalized and clinically applied.

Objective To compare the different ways of alkaline mouthwash slobber use in preventing the oral infection in patients with fever. Methods The patients who satisfied the requirements were involved and randomly divided into A, B and C group. A group did not use alkaline mouthwash; B group prescribed alkaline mouthwash slobber following the doctor's advice; C group received propaganda and demonstration of intensive use of the alkaline mouthwash, and then used the slobber in right way under the surveillance of nurses. The infection rates of oral ulcer and oral leukoplakia were compared and analyzed among the three groups. Results The incidence rates of oral ulcer and oral leukoplakia gradually decreased among the three groups and the differences had statistical significance (χ2=9.243,P=0.010;χ2=6.495,P=0.033).Compared with A group, there was no significant differences in the rates of oral ulcers and oral leukoplakia between Group A and B(OR=0.486, 95%CI:0.113-2.087;OR=0.557, 95%CI: 0.120-2.583), but the incidence rates of oral ulcers and oral leukoplakia gradually decreased(OR=0.024, 95%CI:0.002-0.293;OR=0.036, 95%CI:0.003-0.448)in C group. Conclusions Strengthening use of alkaline mouthwash slobber is more effective in preventing oral infection in patients with fever compared with the routine way of mouthwash use.

Objective To understand the potential risk for schistosomiasis transmission caused by introduction of infection source from mobile population in Shanghai. Methods Field investigation was conducted in the suburb of Shanghai City by screening the mobile population living in Shanghai for more than 1 month and over 1 years old in a procedure of interviewing, serum indirect hemagglutination (IHA) test, and then fecal examination to detect the eggs with nylon sedimentation approach for those IHA positives. Results Among 2 931 mobile people investigated, 1 575 were male (53.74%) and 1 356 were female(46.26%); 138 out of 2 931 were positive in IHA test (4.71%). 1 938 (66.12%) out of 2 931 came from Schistosoma japonicum-endemic provinces and its positive rate in mobile population (5.99%) was significantly higher than those from the transmission-interrupted provinces (2.6%) (?2=10.28, P

Objective To analyze the serum levels of bone morphogenetic protein 4(BMP4)and nerve ax-on guidance factor 4(Netrin-4)in patients with diabetic retinopathy(DR),and to study their relationship with disease stage and prognosis.Methods A total of 186 patients with type 2 diabetes admitted to the hospi-tal from October 2019 to November 2022 were selected as the research objects.According to the presence or absence of retinopathy,they were divided into DR Group(108 cases)and non-DR group(78 cases),and 100 healthy people in the hospital were selected as the control group.According to the stage of DR,the DR pa-tients were divided into stage Ⅰ(19 cases),stage Ⅱ(14 cases),stage Ⅲ(22 cases),stage Ⅳ(23 cases),stage V(18 cases)and stage Ⅵ(12 cases).According to the visual impairment after treatment,the DR patients were divided into a good prognosis group(72 cases)and a poor prognosis group(36 cases).Serum BMP4,Ne-trin-4,fasting plasma glucose(FPG),glycated hemoglobin Alc(HbA1c),systolic blood pressure(SBP),dias-tolic blood pressure(DBP),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C)were detected by enzyme-linked immunosorbent as-say.The serum levels of BMP4 and Netrin-4 in DR patients with different disease stages were analyzed.Multi-variate Logistic regression was used to analyze the influencing factors of DR,and the serum levels of BMP4 and Netrin-4 in DR patients with different prognosis were analyzed.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of poor prognosis in DR patients.Results The FPG,HbA1c,SBP,DBP,TG,TC,BMP4,Netrin-4 levels in DR group were higher than those in control group and non-DR group,while HDL-C level was lower than that in control group and DR group(P＜0.05).There were significant differences in serum BMP4 and Netrin-4 levels between DR patients with different disease stages(P＜0.05).HbA1c,BMP4 and Netrin-4 levels were influencing factors for the occurrence of DR(P＜0.05).The serum levels of BMP4 and Netrin-4 in the poor prognosis group were higher than those in the good prog-nosis group(P＜0.05).The combination of serum BMP4 and Netrin-4 levels in the diagnosis of poor progno-sis of DR patients was better than that of each index alone.Conclusion The serum levels of BMP4 and Ne-trin-4 are increased in DR patients,which can assist in the evaluation of the disease stage of the patients.The combination of BMP4 and Netrin-4 has a good effect in the diagnosis of poor prognosis of patients.

Objective:Molecular mechanisms underlying compound heterozygous mutations in a patient with inherited antithrombin (AT) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in November 2018 with a one-day history of sudden syncope and limb twitching. Peripheral venous blood was collected from the proband and members of his lineages, totaling nine persons across three generations, and a family lineage survey was conducted. AT activity (AT:A) was measured using a chromogenic substrate assay, while AT antigen (AT:Ag) was detected through an immunoturbidimetric assay. Mutation sites were identified by means of Sanger sequencing of the SERPINC1 gene, and silico tools were applied to predict the mutational conservation and hydrophobicity changes. Recombinant plasmid expression vectors were constructed and transfected into HEK293T cells for in vitro overexpression studies. The recombinant AT protein was characterized using Western Blotting, ELISA, and cellular immunofluorescence assays.Results:The proband was a 21-year-old man with type Ⅰ AT deficiency. His AT:A was 33%, along with a corresponding reduction in AT:Ag. The genetic analysis revealed there was a heterozygous insertion mutation at c.318_319insT (p.Asn107*) and a heterozygous missense mutation at c.922G>T (p.Gly308Cys) in exons 2 and 5, respectively. These mutation sites were entirely conserved among the homologous species. Additionally, hydrophobicity studies showed that the p.Gly308Cys mutation will decrease the hydrophilicity of amino acid residues 307-313. The in vitro expression studies indicated a reduction of approximately 46.98%±2.94% and 41.35%±1.48% in the amount of recombinant protein AT-G308C in transfected cell lysates and culture supernatants, respectively. Treatment with the proteasome inhibitor (MG132) restored the cytoplasmic levels of AT-G308C protein to a level similar to that of wild-type protein. However, neither cell lysate nor culture supernatant demonstrated the presence of the recombinant protein AT-N107*. Conclusions:The heterozygous insertion mutation of p.Asn107* and the heterozygous missense mutation of p.Gly308Cys have been associated with reduced AT levels in proband. The p.Asn107* heterozygous insertion mutation may initiate the degradation of mRNA via nonsense mutation-mediated mechanisms, which would remove the defective transcripts, as well as the p.The Gly308Cys heterozygous missense mutation may cause the AT protein to undergo proteasome-dependent degradation by modifying the hydrophobicity of nearby residues in the cytoplasm.

Objective:To analyze the types of genetic variants and clinical characteristics of three Chinese pedigrees affected with Hereditary coagulation factor Ⅶ (FⅦ) deficiency.Methods:Three pedigrees who had visited the First Affiliated Hospital of Wenzhou Medical University between December 2021 and October 2022 were selected as the study subjects. Prothrombin time (PT), activated partial thromboplastin time (APTT) and FⅦ activity (FⅦ: C) were measured in the three probands and their pedigree members. All exons and their flanking sequences were analyzed by direct sequencing, and candidate variants were verified by reverse sequencing. The corresponding variant loci in the family members were also analyzed. ClustalX-2.1-win was used to analyze the conservation of the variant loci. Varcards and Spcards online software was used to predict the pathogenicity of the variants. Pymol software was used to analyze the changes in protein structure and molecular forces.Results:Three cases of hereditary FⅦ deficiency were found to have decreased FⅦ: C, prolonged PT and normal APTT. Genetic analysis identified a total of four genetic variants, and all three probands had harbored compound heterozygous variants of the F7 gene, including p. Cys389Gly and p. His408Gln in proband 1, p. Cys389Gly and IVS6+ 1G>T in proband 2, and IVS6+ 1G>T and IVS1a+ 5G>A in proband 3. Conservation analysis showed that both the p. Cys389 and p. His408 loci are highly conserved among orthologous species. Analysis with Varcards and Spcards software showed that these variants were pathogenic. Protein modeling analysis showed that the p. Cys389Gly and p. His408Gln variants may result in altered protein structures and changes in hydrogen bonds. Conclusion:The clinical manifestations of the three FⅦ-deficient probands may be attributed to the compound heterozygous variants of p. Cys389Gly/p.His408Gln, p. Cys389Gly/ⅠⅤS6+ 1G>T and ⅠⅤS6+ 1G>T/ⅠⅤS1a+ 5G>A of the F7 gene. The combination of the three compound heterozygous variants was unreported previously.

A 34 year old female patient was scheduled to undergo surgical resection due to a "breast nodule". Preoperative examination revealed an activated partial thromboplastin time (APTT) of 66.2 seconds, coagulation factor Ⅺ activity (FⅪ: C) of 2%, and FⅪ antigen (FⅪ: Ag) of 40.3%. The patient and family members showed no abnormal bleeding symptoms. Diagnosed as hereditary coagulation factor Ⅺ deficiency. Genetic testing revealed that the F11 gene had a heterozygous nonsense mutation in exon 10, c.1107C>A (p.Tyr351stop), and a heterozygous missense mutation in exon 13, c.1562A>G (p.Tyr503Cys). The father and son were p Heterozygous carriers of Tyr351stop mutation, while the mother and daughter are p Heterozygous carriers of Tyr503Cys mutations. The in vitro expression results showed that p The Tyr351stop mutation resulted in a significant decrease in the transcription level of F11 gene, while p The Tyr503Cys mutation has no effect on the transcription level and protein expression level of F11 gene, but it leads to a significant decrease in the level of FⅪ:C in the cell culture supernatant.