OBJECTIVE To conduct a comprehensive clinical evaluation of phosphate-lowering drugs in the treatment of chronic kidney disease （CKD） with hyperphosphatemia， and to provide evidence-based support for clinical drug decision-making. METHODS Relevant studies meeting the inclusion and exclusion criteria were retrieved， a comprehensive evaluation of efficacy， safety and economics was conducted based on existing study results. Innovation was analyzed from three aspects including filling the clinical gap， and suitability was assessed from two aspects including technical suitability. Accessibility was evaluated based on the survey data from 37 medical institutions in Kunming， combined with information from the National Reimbursement Drug List and national centralized drug procurement. RESULTS A total of 10 meta-analyses and 2 pharmacoeconomic studies were included. In terms of efficacy， all three categories of phosphate-lowering drugs （calcium-based phosphate binders， non-calcium-based phosphate binders， sodium-hydrogen exchanger 3 inhibitors） effectively reduced serum phosphorus levels. Calcium-based phosphate binders elevated serum calcium levels more significantly； sevelamer was superior to calcium-based phosphate binders in reducing intact parathyroid hormone levels； iron-based phosphate binders improved iron metabolism and anemia-related indicators. In terms of safety， iron-based phosphate binders had the highest incidence of gastrointestinal adverse reactions， followed by lanthanum carbonate. In terms of economics， sevelamer demonstrated economic advantages over calcium-based phosphate binders and lanthanum carbonate. In terms of innovation， non-ca lcium-based phosphate binders addressed the clinical limitation of hypercalcemia associated with calcium-based phosphate binders； iron-based phosphate binders met the treatment needs of patients with comorbid iron deficiency anemia； tenapanor exhibited an innovative phosphorus-lowering mechanism. In terms of suitability， all three categories showed good suitability in various aspects. In terms of accessibility， sevelamer had the highest availability rate， while tenapanor was not yet available in medical institutions. All three categories have been included in the National Reimbursement Drug List ； the prices of lanthanum carbonate and sevelamer decreased substantially following centralized procurement with improved affordability. CONCLUSIONS For CKD patients with hyperphosphatemia， non-calcium-based phosphate binders are preferred， among which sevelamer is recommended as the first-line choice. Lanthanum carbonate may be considered for patients with gastrointestinal intolerance； iron-based phosphate binders are preferred for patients with comorbid iron deficiency anemia； tenapanor may be considered for patients with poor response to or intolerance of conventional regimens； calcium-based phosphate binders are not recommended as long-term first-line therapy.

Objective To study the etiology of a Chinese family with two cases of recessive non-syndromic hearing loss.Methods The clinical data of the family were collected.DNA was extracted from venous blood sam-ples,and whole-exome sequencing were performed to analyze potential causative deafness genes.Sanger sequencing was performed to verify the gene variants.Results There were 5 people among two generations in this family.The proband(Ⅱ-2,9 years old)and her brother(Ⅱ-3)had sensori-neural hearing loss,while their parents had normal hearing.The whole-exome high-throughput sequencing found that the patient carried two mutations in the CDH23 gene:c.4762C＞T(p.ARG1588TRP)and c.6604G＞A(p.ASP2202ASN).According to the American College of medical genetics and genomics(ACMG)genetic variation classification standards and guidelines,both c.6604G＞A and c.4762C＞T variants were identified as pathogenic.Conclusion The new compound heterozygous mutations c.4762C＞T and c.6604G＞A in the CDH23 gene are highly likely to be the causative factors for deafness in this family.

Objective To study the etiology of a Chinese family with two cases of recessive non-syndromic hearing loss.Methods The clinical data of the family were collected.DNA was extracted from venous blood sam-ples,and whole-exome sequencing were performed to analyze potential causative deafness genes.Sanger sequencing was performed to verify the gene variants.Results There were 5 people among two generations in this family.The proband(Ⅱ-2,9 years old)and her brother(Ⅱ-3)had sensori-neural hearing loss,while their parents had normal hearing.The whole-exome high-throughput sequencing found that the patient carried two mutations in the CDH23 gene:c.4762C＞T(p.ARG1588TRP)and c.6604G＞A(p.ASP2202ASN).According to the American College of medical genetics and genomics(ACMG)genetic variation classification standards and guidelines,both c.6604G＞A and c.4762C＞T variants were identified as pathogenic.Conclusion The new compound heterozygous mutations c.4762C＞T and c.6604G＞A in the CDH23 gene are highly likely to be the causative factors for deafness in this family.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

OBJECTIVE: To analyze the expression of microRNA-106a(miR-106a) in renal cell carcinoma (RCC) and its correlation with clinicopathological characteristics and prognosis of patients. METHODS: Serum samples of 64 patients with newly diagnosed RCC were collected as the study group, and serum samples of 40 healthy individuals were used as the control group. Real-time fluorescence quantitative PCR was used to determine the expression level of miR-106a in each group. The correlation between miR-106a expression and clinicopathological characteristics of the patients was studied with single factor analysis and multiple Logistic regression model. Kaplan-Meier survival curve was used to analyze its correlation with the prognosis of patients. RESULTS: Before surgery, compared with the control group (1.17± 0.58), RCC patients with high- (9.15± 0.96) and low-expression(3.45± 0.37) had increased expression of miR-106a. Postoperatively, the expression level of miR-106a in both groups of patients decreased to 1.53± 0.18 and 1.75± 0.21, respectively. The area under the curve (AUC) of the diagnostic value of serum miR-106a for RCC was 0.782 (95% CI: 0.661-0.902). With an optimal cutoff value of 0.531, the sensitivity was 78.10% and the specificity was 75.00%. Serum miR-106a level of RCC patients with TNM stage T3 or T4, clinical stage II or III, lymph node metastasis, and recurrence were significantly increased. The high expression of serum miR-106a in RCC patients has an independent relationship with the tumor TNM stage and lymph node metastasis. Of the 64 follow-up patients, 4 were lost and 30 had died. Among them, the median survival time of patients in the miR-106a high expression group was 30 months, which was significantly shorter than that of the low expression group (52 months). CONCLUSION The serum level of miR-106a is elevated in RCC patients, and may be used as a molecular marker for the diagnosis of RCC. High serum expression of miR-106a is an independent predictor for tumor TNM stage and lymph node metastasis, as well as an independent predictor for poor prognosis of RCC patients.
Biomarkers, Tumor/genetics* ; Carcinoma, Renal Cell/genetics* ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms/genetics* ; MicroRNAs/genetics* ; Neoplasm Recurrence, Local ; Prognosis

As one of the most common pathogens in aquatic animals, Aeromonas hydrophila exhibits a wide range of pathogenicity. Due to factors like unreasonable use of antibiotics and horizontal gene transfer mediated by plasmids, many resistant strains of Aeromonas hydrophila were isolated from ready-to-eat seafood products in retail markets, supermarkets and restaurants. These strains carry many resistance genes. Therefore, it is essential to explore the key control points, and seek for prevention and control strategies so as to effectively alleviate antibiotic resistance. We review here the prevalence of drug resistance of Aeromonas hydrophila in China, and its main infection and resistance mechanisms, and the main means and strategies for reducing and preventing drug resistance. We also address further research directions and focus on drug resistance in Aeromonas hydrophila of the aquatic product.
Aeromonas hydrophila ; drug effects ; Animals ; Anti-Bacterial Agents ; pharmacology ; China ; epidemiology ; Drug Resistance, Bacterial ; Fish Diseases ; epidemiology ; microbiology ; Fisheries ; Fishes ; Gram-Negative Bacterial Infections ; epidemiology ; microbiology ; Research

Objective To explore the influence of agricultural mechanization progress on epidemic intensity of hemorrhagic fever with renal syndrome (HFRS) so as to provide reference for prevention and control of HFRS in rural areas.Methods Data of HFRS epidemics and agricultural mechanization progress of Qingdao City and five main epidemic areas of HFRS were collected by retrospective analysis methods.Agricultural mechanization progress,time distribution,incidence rate of HFRS and capture rate of rats were compared,respectively.Risk factors were analyzed by case-control study using simple random sampling method.Cases of case group were selected from HFRS cases of Jiaonan County recovered between 2012 and 2013.The control group was healthy residents with a equal number of the case group.Residential locations,work ways,rodent infestation at work locations and in residential areas and skin injury conditions were surveyed by a household questionnaire survey.Results Agricultural machinery gross power of Qingdao City was developed from 174.76 megawatts of electricity (mwe) in 1985 to 854.00 mwe in 2015.The comprehensive mechanization degree marched from 60.0％ in 1994 to 90.2％ in 2015.HFRS incidence in Qingdao City declined from the first epidemic peak (1986) of 32.97/100 000 to the third peak (2012) of 3.54/100 000.HFRS incidence in Jiaonan,Jiaozhou,Pingdu,Laixi,Jimo cities reduced from the first epidemic peak (1985 or 1986) of 101.25/100 000,86.37/100 000,35.80/100 000,11.55/100 000,8.13/100 000 to the third peak(2012) of 14.68/100 000,4.43/100 000,2.33/100 000,6.02/100 000,3.26/100 000.The platform stage of epidemic peak in autumn and winter shortened from 4 or 5 months to 2 months.The capture rate of rats fluctuated around 2％.The infection risk of small farm implements or handwork was greater than huge mechanization (OR =0.01,P ＜ 0.01).Conclusions Agricultural mechanization changes the agricultural activity patterns to a large extent and lowers the HFRS epidemic by minimizing the risk of infection and shortening the platform stage of epidemic peak.The higher the degree of mechanization,the lower the epidemic intensity.

Objective:To investigate the feasibility of periodontal mechanical therapy for chronic periodontitis and coronary heart disease patients with low dose of aspirin.Methods:Sixty nine chronic periodontitis patients with coronary heart disease were randomly selected as the experimental group (medication group,group A),the control group (withdrawal group,group B) including 20 chronic periodontitis patients with coronary artery disease,stopping the drug for one week and another control group with 50 chronic periodontitis patients (group C).The three groups were examined with pocket probing,and received supragingival scaling,subgingival scaling,and root planning.Local bleeding after operation was observed.In 30 minutes after periodontal mechanical treatment,there was still a need to take some hemostatic measures (containing the oxidized cellulose putting in the periodontal pocket,gauze oppressing,and suturing).Nd:YAG laser was used to stop bleeding 60 minutes after operation.Results:At baseline,there was no significant difference in the three groups,as to the plaque index (PLI),the probing depth (PD),and the attachment loss (AL).The bleeding index (BI)in group A was significantly higher than that in group C (P =0.024),higher than that in group B (P =0.088).The platelet maximum aggregation rate (Aggmax) was detected in some subjects.The average Aggmax value group A was 15.2％,which was much greater than that in group B (60.7％) and group C (62.5 ％).The three groups were all safe in the treatment of periodontal therapy.There were five cases of active bleeding in group A,one case in group B and one case in group C in 30 minutes after operation.In 60 minutes after operation,there was one case of bleeding actively in group A.Nd:YAG laser was used to stop bleeding successfully.Conclusion:The chronic periodontitis and coronary heart disease patients with long-term oral administration of low dose of aspirin can be safely treated with periodontal mechanical treatment,and the effect of local hemostasis is positive without stopping the drug.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

BACKGROUNDThe occurrence and development of aortic aneurysm (AA) are associated with infection. Some researchers have detected the DNA of periodontal pathogens in AA samples in certain populations. However, it has not been done in Chinese population. The objective of this study was to evaluate the prevalence of periodontal pathogens in oral tissue samples and aneurysm samples of AA patients.

METHODSEighty-nine subjects with AA and 59 subjects without AA were examined. Periodontal clinical parameters were evaluated. Unstimulated saliva and subgingival plaque samples were collected from all subjects. Twenty-six dissected AA samples were obtained. Evidence of eight periodontal pathogens including Porphyromonas gingivalis (Pg), Actinobacillus actinomycetemcomitans (Aa), Prevotella intermedia (Pi), Tannerella forsythensis (Tf), Treponema denticola (Td), Campylobacter rectus (Cr), Fusobacterium nucleatum (Fn), and Prevotella nigrescens (Pn) was ascertained in all samples by 16S rRNA-based polymerase chain reaction (PCR) assay.

RESULTSThe periodontal indexes including plaque index (PLI), probing depth (PD), bleeding index (BI), and clinical attachment loss (CAL), of the six Ramfjord index teeth were significantly higher in the AA group than those in the control group (P < 0.01). Eight periodontal pathogens in subgingival plaque samples were more frequently detected in the AA group than in control group. The difference in prevalence between the groups was significant for six (out of eight) periodontal pathogens assayed (Pg, Pi, Fn, Pn, Tf, and Td, P < 0.01). Additionally, all eight periodontal pathogens were more frequently detected in saliva samples of the AA group than in those of the control group, again with six (out of eight) (Pg, Pi, Fn, Cr, Tf, and Td) displaying significant differences in prevalence between the two groups (P < 0.01). Out of 26 aneurysm samples examined, Pg, Pi, Fn, Cr and Tf were detected in 6 (23.1%), 2 (7.7%), 3 (11.5%), 1 (3.8%), 2 (7.7%), respectively, and Aa, Pn, and Td were not detected in dissected aneurysm samples.

CONCLUSIONResults of this study suggested that periodontal infection is associated with the occurrence of AA.

Aged ; Aggregatibacter actinomycetemcomitans ; genetics ; pathogenicity ; Aortic Aneurysm ; microbiology ; Female ; Humans ; Male ; Middle Aged ; Periodontitis ; microbiology ; Porphyromonas gingivalis ; genetics ; pathogenicity ; Prevotella intermedia ; genetics ; pathogenicity ; RNA, Ribosomal, 16S ; genetics ; Treponema denticola ; genetics ; pathogenicity