By sorting out the differences and connections between family doctor teams and specialized disease teams, role competency and mutual collaboration, and introducing the learning health system (LHS) mechanism, a comprehensive operating system for community general practice learning organizations based on LHS was constructed, focusing on five single disease types. The system includes a combination of general and specialized medicine that links three levels of medical institutions, thereby opening up the business cooperation process between professionals in different institutions, and establishing a sustainable collaboration mechanism. This allows medical institutions at three levels to continuously tap the potential of their disciplines, achieve their own ability growth and feel higher work value, and also bring better health solutions to residents, guided by the common goal of "health centered, patient centered".

This paper reports the clinical characteristics and ZNF526 gene mutation in a child with Dentici-Novelli neurodevelopmental syndrome, who was admitted to the Department of Pediatrics at the First Affiliated Hospital of Henan University of Traditional Chinese Medicine in June 2021, and reviews the relevant literature.The male child, 5 years and 1 month old, presented with distinctive facial features, intellectual and motor retardation, language development delays, scattered Mongolian spots on the back and buttocks, brain tissue involvement, visual impairment, and epilepsy.The whole-exome sequencing of the family revealed that the child suffered compound heterozygous mutations, c.1430G>T and c. 475C>T, in the ZNF526 gene.At present, 7 mutation sites in the ZNF526 gene have been reported globally to be associated with neurodevelopmental disorders, and the 2 mutations in this case have not been reported in the literature, broadening the phenotype and mutation spectrum of this disease.

Objective:To investigate the current status of pertussis laboratory diagnosis and confirmed pertussis cases reporting in Shaanxi Province, and evaluate the quality of case reports.Methods:The information of confirmed pertussis cases reported in Shaanxi Province from January to July 2022 was collected through the China Disease Control and Prevention Information System. The laboratory diagnostic methods and pertussis vaccine immunization history of confirmed cases were investigated, and the descriptive epidemiological method was used for statistical description.Results:Of the 164 confirmed cases of pertussis reported from January to July 2022, two were not tested in the laboratory and 162 were tested in the laboratory. The proportions of different detection methods were 1.85% (3/162) of isolation and culture, 31.48% (51/162) of serum antibody IgG, 14.20% (23/162) of serum antibody IgM, 49.38% (80/162) of serum antibody PCR and 3.09% (5/162) of serum antibody IgM+ PCR. Among the 79 serological positive cases, 12 cases (15.19%)had no history of pertussis immunization, and 15 cases (18.99%), 11 cases (13.92%) and 41 cases (51.90%) had the time interval from vaccination to detection of <1 year, 1-3 years and >3 years, respectively. Based on the analysis of laboratory testing methods and vaccination history, 38 cases were misdiagnosed/misreported among 164 cases, with a misdiagnosis or misreported rate of 23.17%. There were 17, 12 and 9 cases of misdiagnosis/misreport in 0-2 years old group, 3-6 years old group and≥7 years old group, and the misdiagnosis or misreported rates were 27.42%(17/62), 26.67%(12/45) and 15.79%(9/57), respectively.Conclusions:The selection of pertussis laboratory testing methods in some medical institutions in Shaanxi Province is incorrect, which leads to a certain proportion of misdiagnosis or misreport, and it is necessary to further strengthen the training and standardization.

A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating Clostridium butyricum spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded. Following oral administration, CBS germinated into Clostridium butyricum (CB) and colonized in the colon. Combined with colonic specifically β-glucosidase responsive degrading of CS, dual colon-specific release of liposomes was achieved. And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold. Simultaneously, the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria. Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB, the intratumoral pathogenic bacteria were eliminated fundamentally, blocking their recruitment to immunosuppressive cells. Furtherly, synchronized with lipopolysaccharide (LPS) released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells, they jointly enhanced tumor infiltration of CD8⁺ T cells and reactivated robust antitumor immunity.

Objective:To investigate the prognostic value of systemic immune-inflammation index (SII) in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:The clinical data, including age, gender, complications, laboratory examination results post-admission, SII, model for end-stage liver disease (MELD) score, MELD-Na score, Child-Turcotte Pugh (CTP) score of HBV-ACLF patients treated in Huashan Hospital, Fudan University from January 2016 to August 2021 were retrospectively analyzed. The patients were divided into survival group and death group according to the outcome at 90 days of follow-up.Paired sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis.Pearson correlation was used to analyze the correlation between SII and the prognosis prediction model of HBV-ACLF. The area under the curve (AUC) was used to analyze the clinical efficacies of SII, MELD score, MELD-Na score and CTP score in predicting the prognosis of HBV-ACLF patients, and the optimal cut-off value of SII for predicting the prognosis of HBV-ACLF was calculated. Kaplan-Meier method was used for survival analysis. Results:A total of 140 patients with HBV-ACLF were included. There were 88 patients in the survival group, including 65 males and 23 females, with the age of (47.69±11.96) years. There were 52 cases in the death group, including 40 males and 12 females, with the age of (52.73±12.22) years. The age, aspartate aminotransferase, total bilirubin, serum creatinine, international normalized ratio, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, SII, MELD score, MELD-Na score, CTP score and the incidence of infection in the death group were all significantly higher than those in the survival group, and albumin, lymphocyte count, platelet count, prognostic nutritional index in the death group were all significantly lower than those in the survival group, and the differences were all statistically significant ( t=-2.39, Z=-2.84, t=-4.81, Z=-2.15, Z=-4.91, Z=-3.47, Z=-3.36, Z=-3.83, Z=-4.69, Z=-4.56, Z=-6.31, χ2=24.96, t=3.06, t=3.03, Z=-7.57 and t=4.12, respectively, all P<0.05). Pearson correlation analysis showed that SII was positively correlated with CTP score ( r=0.272 7, P=0.001), MELD score ( r=0.365 8, P<0.001) and MELD-Na score ( r=0.381 1, P<0.001). The AUC of SII was the largest of 0.80, and 0.76 for MELD score, 0.74 for MELD-Na score and 0.73 for CTP score. The optimal cut-off value of SII was 447.49. Kaplan-Meier analysis showed that the 90 days survival rate of patients with SII≥447.49(38.60%(22/57)) was lower than that of SII<447.49 group (79.52%(66/83)), and the difference between the two groups was significant ( χ2=23.80, P<0.001). Conclusions:SII can be used to assess the severity and prognosis of HBV-ACLF patients. SII ≥447.49 indicates poor prognosis.

We report a family of glucocorticoid-remediable aldosteronism (GRA). A 20-year-old man presented with early-onset hypertension accompanied by hypokalemia was admitted to our hospital. Clinical data and family history were collected. Following genetic analyses with PCR and Sanger sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located in 264-380 nucletide, which was considered as GRA. There were 4 cases of GRA in the family, the average age of onset was 28 years, and all had different degrees of hypertension. Among them, the proband′s uncle suffered from moyamoya disease and died 6 months later due to sudden cerebral hemorrhage. In order to improve the understanding of this rare disease, the pathogenesis, biochemical profiles, diagnosis and treatment of GRA were summarized and analyzed.

Objective:To compare the in vitro susceptibility of fluconazole-resistant Candida albicans strains from superficial and deep infections to 8 antifungal drugs, and to compare drug resistance mutations in these strains. Methods:According to the Clinical and Laboratory Standards Institute (CLSI) protocol M27-A4, 26 deep infection-derived and 33 superficial infection-derived drug-resistant Candida albicans strains were tested for in vitro susceptibility to 8 antifungal drugs (fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B, fluorocytosine, terbinafine, and micafungin) alone or in combination. DNA was extracted from all drug-resistant strains, and mutations in 3 drug resistance genes, including ERG3, ERG11 and FUR1, were detected by PCR. Normally distributed measurement data with homogeneous variance were compared between two groups by using two-independent-sample t test, non-normally distributed measurement data with non-homogeneous variance were compared using Mann-Whitney U test, and enumeration data were compared using chi-square test. Results:The minimum inhibitory concentrations (MICs) of fluconazole, itraconazole, voriconazole, posaconazole and fluorocytosine all significantly differed between the superficial infection group and deep infection group (all P < 0.05) , while there was no significant difference in the MIC of amphotericin B or micafungin between the two groups (both P > 0.05) . The MIC of terbinafine was >64 μg/ml in 96.6% of the above strains, so could not be compared between groups. As combination drug susceptibility testing revealed, the combination of terbinafine with azoles (fluconazole, voriconazole, itraconazole or posaconazole) showed synergistic inhibitory effects against 15 Candida albicans strains (7 strains from deep infections, 8 strains from superficial infections) , with fractional inhibitory concentration (FIC) indices being 0.033 to 0.187; no marked synergistic effect was observed in the combinations between fluorocytosine and azoles, between fluorocytosine and amphotericin B, or between amphotericin B and fluconazole, with the FIC indices being 0.56 to 1.125. The missense mutation V351A in the ERG3 gene was identified in all the 33 (100%) superficial infection-derived strains, as well as in 13 (50%) deep infection-derived strains, and the mutation A353T in the ERG3 gene was identified in 4 (15%) deep infection-derived strains; as for the ERG11 gene, missense mutations identified in the superficial infection-derived strains included I437V (32 strains, 97%) , Y132H (23 strains, 70%) , T123I (16 strains, 48%) , K128T (6 strains, 18%) , D116E (5 strains, 15%) , A114S (4 strains, 12%) , E266D (2 strains, 6%) , G448E (2 strains, 6%) , and G465S (2 strains, 6%) , while missense mutations identified in the deep infection-derived strains included I437V (23 strains, 88%) , E266D (13 strains, 50%) , E260G (5 strains, 19%) , and V488I (4 strains, 15%) ; the missense mutation R101C in the FUR1 gene was identified in 11 (33%) superficial infection-derived strains, but not identified in deep infection-derived strains. Conclusion:The drug susceptibility and drug resistance mutations differed to some extent between superficial infection- and deep infection-derived fluconazole-resistant Candida albicans strains.

Objective : The CRISPR / dCas9-SAM system was used to explore genes related to the proliferation of gastric cancer cells AGS，and their role in the occurrence and development of gastric cancer was analyzed． Methods : sgRNA was designed for genes with differential expression between gastric cancer and normal gastric tissue， and a lentiviral library was obtained after packaging was constructed．The AGS cells at different time points after the library was infected with AGS cells were used as the screening pressure，and the AGS cells at three time points on days 0，7 and 14 were collected．High-throughput sequencing analyzed sgRNA enrichment in AGS cells at dif- ferent time points after infection to obtain differential genes related to AGS cell proliferation. Results : Bioinformat- ics showed that compared with the 0 d group，42 and 45 negative screening differential genes and 59 and 40 posi- tive screening differential genes were obtained in the 7 d group and 14 d group，respectively．Among them，the 7 d group and the 14 d group had 11 genes in the negative screening and the positive screening． Conclusion In this study，11 genes inhibiting the proliferation of AGS cells were screened，of which 5 were protein-coding genes and 6 were long non-coding RNA ( lncRNA ) genes． 11 candidate genes that promoted AGS cell proliferation were screened，of which 3 were protein-coding genes and 8 were lncRNA genes．It laid a foundation for further function- al verification and comprehensive analysis of the occurrence and development process of gastric cancer.

Objective To investigate the management of Graves' disease in Jiangsu province. Methods According to the 2011 management of GD survey from American Thyroid Association and the 2013 survey from European Thyroid Association, a questionnaire was designed for this survey to acquire the diagnosis, treatment, and follow-up of Graves' disease among endocrinologists from 35 tertiary hospitals in Jiangsu province. Results A total of 476 valid questionnaires were collected. For patients with symptoms of hyperthyroidism, a large majority of respondents monitored serum FT3 , FT4 , TSH, thyroid peroxidase antibody, thyroglobulin antibody, TSH receptor antibody, and finding of thyroid ultrasound, accounted for 95. 6％, 95. 0％, 95. 4％, 95. 8％, 90. 3％, 90. 5％, and 93. 9％physicians, respectively. 91.2％ of physicians preferred anti-thyroid drugs as the first-line treatment, and 92. 6％ of them gave priority to the use of methimazole. For the duration of anti-thyroid drugs therapy, 41.2％of endocrinologists chose 24 months, while 20％ chose 18 months. When patients have moderate and active ophthalmopathy, most respondents with medium or senior professional titles preferred anti-thyroid drugs, while most resident physicians chose radioactive iodine plus corticosteroids. When pregnancy was confirmed in the patients of Graves' disease, 88％ of respondents preferred propylthiouracil during the first trimester of pregnancy, and 58. 4％ of them would continue propylthiouracil into the second trimester. Conclusions The mastering of basic perception of Graves' disease knowledge is satisfactory among the endocrinologists. But by comparing to the American and European survey results and related guidelines, there are still some differences in diagnosis and treatment. Therefore, physicians should notice those differences and make improvement on standardized treatment for patients to raise the response ratio while reducing the recurrent events.

Objective To investigate the clinical characteristics,diagnosis and treatment strategies of breast neuroendocrine carcinoma.Methods 20 cases with breast neuroendocrine carcinoma,who were admitted in Department of Breast Surgery,the Second Affiliated Hospital of Dalian Medical University from Mar.2005 to Dec.2017,were analyzed retrospectively.Results The average age of the 20 patients was(54.35±13.35) years.In aspect of surgery,18 patients received modified radical mastectomy,1 patient received total glandectomy and sentinel lymph node biopsy and stage I silicone implant breast reconstruction,and 1 patient received radical mastec tomy.In terms of pathological types,there were 5 cases (25.0％) of highly differentiated neuroendocrine carcinoma,4 cases (20.0％) of poorly differentiated neuroendocrine carcinoma (small cell carcinoma),and 11 cases (55.0％)of invasive breast cancer with neuroendocrine differentiation.In molecular typing,there were 7 cases (35.0％) of Luminal A,7 cases (35.0％) of Luminal B (HER2 negative),4 cases (20.0％) of Luminal B (HER2 positive),and one case(5.0％) of HER2 type and one case(5.0％) of Basal-like type.The positive rates of ER,PR and HER2 in this group were 90.0％,60.0％ and 25.0％ respectively.20 patients were followed up for 5 to 119 months,with an average follow-up of (59.85±24.51) months.One patient developed bone metastases in the 6th year after surgery and survived for 119 months.One patient developed pulmonary metastasis at the 20th month after surgery and died at the 28th month after surgery.So far,the remaining postoperative patients still survived and no sign of recurrence or metastasis was found.Conclusion The diagnosis of breast neuroendocrine carcinoma relies on histopathological and immunohistochemical detection.Its ER/PR positive rate is high,its molecular typing is mostly Luminal type,and neoadjuvant treatment can be performed when necessary.For specific patients whose ER or PR are positive,neoadjuvant endocrine therapy is also a well-established therapy,even the optimal results can be achieved.However,more cases are still needed for research.