Objective:To explore the significance of genetic diagnosis, clinical characteristics and treatment of congenital renal diabetes insipidus with arginine vasopressin receptor 2 ( AVPR2). Methods:Clinical data of three patients diagnosed as diabetes insipidus were retrospectively analyzed.Results:The three cases were 3-month, 5-month and 6-month male infants, respectively. The main manifestations were repeated fever and growth retardation with hypernatremia. Polydipsia, polyuria and persistent hypogravity uria appeared during the course . In case 1, the AVPR2 exon c.613_c.614del resulted in amino acid change p.Y205Cfs*53. The proband mother was a mutation carrier of AVPR2 gene, and the child was hemizygous and the mother was heterozygous. In case 2, there was a hemizygotic mutation in AVPR2 gene: c.255C>A(p.SP85Glu), which appeared to be a missense mutation. The father had no mutation, the mother had a heterozygous mutation, the aunt had no mutation, and the eldest brother had a hemizygous mutation. There was one hemizygotic variation in the AVPR2 gene in patient 3: c.167G>A(P.LY56ASP), which was a missense mutation. The father had no mutation, the mother had a heterozygous mutation. The minimum allele frequencies of the gene variants in case 2 and case 3 were not recorded in the reference population gene frequency database. The urine volume of 3 children was significantly reduced after treatment with hydrochlorothiazide and amiloride.After genetic test, all three cases were diagnosed as congenital renal diabetes insipidus caused by AVPR2 gene mutation. Conclusion:Genetic testing benefits to the early diagnosis of congenital renal diabetes insipidus.

Objective:To investigate the association between short-term blood pressure variability(BPV)and all-cause mortality in elderly patients with early sepsis-associated acute kidney injury(SA-AKI).Methods:A retrospective study was conducted on elderly patients with early SA-AKI from the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ)database between 2008 and 2022.All patients were divided into four groups(Q1-Q4)according to the quartiles of the 24-hour systolic blood pressure coefficient of variation(SBPCV): Q1(SBPCV<8.69%), Q2(8.69%≤SBPCV<10.84%), Q3(10.84%≤SBPCV<13.64%), Q4(SBPCV≥13.64%). Cox regression analysis was used to assess the association between SBPCV and one-year all-cause mortality.Restricted cubic spline regression was used for non-linear testing, and threshold effect analysis was further performed for non-linear relationships.Results:A total of 5 955 elderly patients were included in the study, and 2 746(46.11%)patients died within one year following the diagnosis of early SA-AKI.Patients in groups Q1 to Q4 had one-year all-cause mortality rates of 46.34%(690/1 489), 45.56%(678/1 488), 42.47%(632/1 488), and 50.07%(746/1 490), respectively.After adjusting for relevant confounding variables, Cox regression analysis showed that the Q1 group and Q4 group had a 26%( HR=1.26, 95% CI: 1.13-1.41, P<0.001)and 12%( HR=1.12, 95% CI: 1.01-1.24, P=0.047)higher risk of one-year mortality compared to the Q3 group, respectively.SBPCV and one-year all-cause mortality showed a U-shaped non-linear manner( P for nonlinear<0.001). Threshold effect analysis indicated that when SBPCV<13.07%, each standard deviation increase in SBPCV was associated with a 15% reduction in mortality risk( HR=0.85, 95% CI: 0.78-0.92, P<0.001); conversely, when SBPCV>13.07%, each standard deviation increase in SBPCV was associated with an 11% increase in mortality risk( HR=1.11, 95% CI: 1.03-1.21, P=0.011). Conclusions:Short-term BPV may be associated with long-term all-cause mortality in elderly patients with early SA-AKI in a U-shaped manner.However, these findings require further confirmation through high-quality prospective studies.

Objective:To investigate the association between short-term blood pressure variability(BPV)and all-cause mortality in elderly patients with early sepsis-associated acute kidney injury(SA-AKI).Methods:A retrospective study was conducted on elderly patients with early SA-AKI from the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ)database between 2008 and 2022.All patients were divided into four groups(Q1-Q4)according to the quartiles of the 24-hour systolic blood pressure coefficient of variation(SBPCV): Q1(SBPCV<8.69%), Q2(8.69%≤SBPCV<10.84%), Q3(10.84%≤SBPCV<13.64%), Q4(SBPCV≥13.64%). Cox regression analysis was used to assess the association between SBPCV and one-year all-cause mortality.Restricted cubic spline regression was used for non-linear testing, and threshold effect analysis was further performed for non-linear relationships.Results:A total of 5 955 elderly patients were included in the study, and 2 746(46.11%)patients died within one year following the diagnosis of early SA-AKI.Patients in groups Q1 to Q4 had one-year all-cause mortality rates of 46.34%(690/1 489), 45.56%(678/1 488), 42.47%(632/1 488), and 50.07%(746/1 490), respectively.After adjusting for relevant confounding variables, Cox regression analysis showed that the Q1 group and Q4 group had a 26%( HR=1.26, 95% CI: 1.13-1.41, P<0.001)and 12%( HR=1.12, 95% CI: 1.01-1.24, P=0.047)higher risk of one-year mortality compared to the Q3 group, respectively.SBPCV and one-year all-cause mortality showed a U-shaped non-linear manner( P for nonlinear<0.001). Threshold effect analysis indicated that when SBPCV<13.07%, each standard deviation increase in SBPCV was associated with a 15% reduction in mortality risk( HR=0.85, 95% CI: 0.78-0.92, P<0.001); conversely, when SBPCV>13.07%, each standard deviation increase in SBPCV was associated with an 11% increase in mortality risk( HR=1.11, 95% CI: 1.03-1.21, P=0.011). Conclusions:Short-term BPV may be associated with long-term all-cause mortality in elderly patients with early SA-AKI in a U-shaped manner.However, these findings require further confirmation through high-quality prospective studies.

Objective:To explore the significance of genetic diagnosis, clinical characteristics and treatment of congenital renal diabetes insipidus with arginine vasopressin receptor 2 ( AVPR2). Methods:Clinical data of three patients diagnosed as diabetes insipidus were retrospectively analyzed.Results:The three cases were 3-month, 5-month and 6-month male infants, respectively. The main manifestations were repeated fever and growth retardation with hypernatremia. Polydipsia, polyuria and persistent hypogravity uria appeared during the course . In case 1, the AVPR2 exon c.613_c.614del resulted in amino acid change p.Y205Cfs*53. The proband mother was a mutation carrier of AVPR2 gene, and the child was hemizygous and the mother was heterozygous. In case 2, there was a hemizygotic mutation in AVPR2 gene: c.255C>A(p.SP85Glu), which appeared to be a missense mutation. The father had no mutation, the mother had a heterozygous mutation, the aunt had no mutation, and the eldest brother had a hemizygous mutation. There was one hemizygotic variation in the AVPR2 gene in patient 3: c.167G>A(P.LY56ASP), which was a missense mutation. The father had no mutation, the mother had a heterozygous mutation. The minimum allele frequencies of the gene variants in case 2 and case 3 were not recorded in the reference population gene frequency database. The urine volume of 3 children was significantly reduced after treatment with hydrochlorothiazide and amiloride.After genetic test, all three cases were diagnosed as congenital renal diabetes insipidus caused by AVPR2 gene mutation. Conclusion:Genetic testing benefits to the early diagnosis of congenital renal diabetes insipidus.

Objective To investigate the effect of ankyrin-repeat domain-containing protein 22(ANKRD22)on the proliferation,invasion,and migration of human hepatoma cells and its molecular mechanism.Methods The TCGA database was used to analyze the expression level of ANKRD22 in normal liver tissue and hepatocellular carcinoma tissue and its association with prognosis.Western Blot and qRT-PCR were used to measure the expression of ANKRD22 in human normal liver cells(L-02)and human hepatoma cells(Huh7,HepG2,MHCC-97H,SK-HEP-1,and SMMC-7721);CCK-8 assay,EdU,wound healing assay,and Transwell assay were used to observe the effect of ANKRD22 on the proliferation,invasion,and migration of hepatoma cells;Western Blot was used to investigate the association of ANKRD22 with cyclins and EMT-related proteins;KEGG and ssGSEA analyses were performed to investigate the mechanism of action of ANKRD22 in hepatoma cells,and related experiments were conducted for validation.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.Results In the TCGA database,the expression level of ANKRD22 in hepatoma tissue was significantly higher than that in normal liver tissue(t=5.083,P<0.05),and the patients with a high expression level of ANKRD22 had longer overall survival and disease-related survival than those with a low expression level of ANKRD22(P<0.05).The expression level of ANKRD22 in various human hepatoma cell lines was higher than that in human normal liver cells(all P<0.05).Cell proliferation assay showed that the ANKRD22 overexpression group had significantly higher EdU positive rate and proliferation rate than the Vector group(t=19.60 and 6.72,both P<0.001),and compared with the si-NC group,the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower EdU positive rate and proliferation rate(all P<0.001).Compared with the Vector group,the overexpression group had significantly higher expression levels of Cyclin E1,Cyclin D1,CDK7,and CDK4(t=3.54,4.95,6.34,and 5.19,all P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001).The overexpression group had a significantly lower expression level of P27 than the Vector group(t=6.12,P<0.001),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group(both P<0.001).Invasion and migration experiments showed that compared with the Vector group,the ANKRD22 overexpression group had significantly higher migration rate and number of crossings through the membrane(migration group and invasion group)(t=5.01,25.60,and 3.67,all P<0.05),and compared with the si-NC group,thesi-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower migration rate and number of crossings through the membrane(migration group and invasion group)(all P<0.01).The overexpression group had significantly higher expression levels of N-cadherin,Vimentin,and Snail than the Vector group(t=12.13,8.85,and 13.97,all P<0.001),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001);the overexpression group had a significantly lower expression level of E-cadherin than the Vector group(t=4.98,P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group(both P<0.001).The KEGG enrichment analysis and the ssGSEA analysis showed that ANKRD22 was associated with the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma,and the overexpression group had significantly higher expression levels of p-AKT/AKT,p-PI3K/PI3K,and p-mTOR/mTOR than the Vector group(t=12.21,3.43,and 9.75,all P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001).Conclusion ANKRD22 is highly expressed in hepatoma cells and can promote the proliferation,invasion,and migration of hepatoma cells and the activation of the PI3K/AKT/mTOR signaling pathway.

Systemic juvenile idiopathic arthritis is one of the common rheumatic and immune diseases in children. It has a sudden onset, obvious systemic symptoms, and lung involvement. However, systemic juvenile idiopathic arthritis with an early manifestation of pulmonary ground-glass opacities combined with macrophage activation syndrome is rare. The clinical data of a child with systemic juvenile idiopathic arthritis with pulmonary ground-glass shadow and macrophage activation syndrome who was admitted to Hubei Maternal and Child Health Care Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology in December 2021 were analyzed retrospectively in order to improve the understanding of rheumatic diseases and pulmonary lesions. The child was admitted to the hospital for 10 days due to rash and fever. Thoracic CT showed scattered ground glass like shadows in both lungs due to the prevention and control screening of COVID-19 pneumonia epidemic situation. After admission, the child was still repeatedly flaccid with high fever, accompanied by dysfunction of both lower limbs. The knee joint MRI found that there was synovitis in the knee joint, and various laboratory indicators suggested macrophage activation syndrome. After that, systemic juvenile idiopathic arthritis was diagnosed. After being treated with methylprednisolone, cyclosporine and topzumab, the clinical remission and the ground-glass shadow of the lung basically disappeared. Through the analysis of this case, it is suggested that clinicians should not ignore other diseases that cause ground glass shadow in the lung during the current epidemic of COVID-19.

METHODS: Rat BMSCs were isolated, cultured and identified. The time-dependent expressions of TSP-2 and Sox9 in BMSCs under a dynamic mechanical pressure of 0–120 kPa at 0.1 Hz for 1 h were tested by qPCR and Western blotting. The role of TSP-2 in chondrogenic differentiation of BMSCs under mechanical pressure was validated by using small interfering RNA. The impact of TSP-2 and mechanical pressure on chondrogenesis were detected and the downstream signaling molecules were explored using Western blotting. RESULTS: Mechanical pressure stimulation of 0–120 kPa for 1 h significantly upregulated the expression of TSP-2 in BMSCs. The expression of the chondrogenesis markers Sox9, Aggrecan, and Col-II were all upregulated under dynamic mechanical pressure or TSP-2 stimulation. Additional exogenous TSP-2 may potentiate the chondrogenic effect of mechanical stimulation. After knock down TSP-2, the upregulation of Sox9, Aggrecan and Col-II under mechanical pressure was inhibited. The NF-jB signaling pathway responded to both dynamic pressure and TSP-2 stimulation, and the cartilage-promoting effect was blocked by an NF-jB signaling inhibitor. CONCLUSION TSP-2 plays an essential role in the chondrogenic differentiation of BMSCs under mechanical pressure. NF-jB signaling is involved in the mechano-chemical coupling of TSP-2 and mechanical pressure for the chondrogenic differentiation of BMSCs.

Objective:To investigate the correlation between sleep quality and risk of female complicated vulvovaginal candidiasis (VVC).Methods:From January 2021 to June 2021, patients in the gynecological clinic of Xiangya Hospital of Central South University were continuously enrolled as the research objects using a cross-sectional survey. A self-made questionnaire was used to collect the age, marital status, education level, family monthly income, place of residence in the past two years, maternity history, number of births, intrauterine device, number of abortions, frequency of sex life, use of contraceptives within two months, use of antibacterial drugs within two weeks. Generalized Anxiety Disorder Scale, Patient Health Questionnaire, Health Questionnaire Somatic Symptom Group Scale, Pittsburgh Sleep Quality Index were used to collect patients′ anxiety, depression, somatization symptoms, and sleep quality conditions. The total scores of sleep quality and the scores of each dimension were used as observation indicators. Three logistic regression analysis models were constructed to explore the relationship between sleep quality and complicated VVC groups.Results:Patients in the complex VVC group were significantly higher in age, married, middle school education, rural area of residence in the last two years, birth history, number of births ≥3, sexual frequency≥1/week, and no antibiotic use within two weeks compared to those in the control group (all P<0.05). Without adjusting for confounding factors, women with poor subjective sleep quality had a 6.73-fold increased risk ( OR=7.73, 95% CI: 3.22-18.55) of complex VVC compared with those with good subjective sleep quality. After adjusting for confounding factors, the risk was further increased to 9.08 fold ( OR=10.08, 95% CI: 3.47-29.33)(all P<0.05). Compared with women without sleep disorders, women with mild sleep disorders had a 97% increased risk of complex VVC ( OR=1.97, 95% CI: 1.15-3.37). After adjusting for confounders, the risk remained 97% higher ( OR=1.97, 95% CI: 1.10-3.55)(all P<0.05). Conclusion:Poor subjective sleep quality and mild sleep disorder may be associated with the risk of complex VVC.

Objective:To explore the value of metal artifact reduction in oblique sagittal multi-acquisition with variable resonance image combination slab selectivity (MAVRIC-SL) inversion recovery (IR) sequence compared with conventional fast spin-echo (FSE) fat saturation (FS)-T 2WI and proton density weighted imaging (PDWI) on the postoperative review of patients with metal-fixed anterior cruciate ligament reconstruction (ACLR) at 3.0 T MR. Methods:From June to November 2018, 27 patients with metal fixtures in ACLR were prospectively recruited in the First Hospital of China Medical University. The FSE sequences (FS-T 2WI and PDWI) and the MAVRIC-SL IR were performed at 3.0 T MRI system. The maximum artifact slice was selected and ROI was drawn, then the implant and artifact area and the number of artifact-influence slices were recorded. Image signal-to-noise ratio (SNR) was calculated. The degree of image artifacts (artifact degree of spiked ligament staple and its influence on the diagnosis of surrounding structures), measurability (measurability of distance between the upper edge of the staple and the lower edge of the graft entrance on tibia), and other degree of artifacts (whether there were metal artifacts other than implants that affect the observation of other structures within the scanning range) were scored. The Friedman M test and pairwise comparison were used to compare and analyze the quantitative and qualitative data. Results:The differences in artifact area, the number of artifact-influence slices and SNR among FS-T 2WI, PDWI and MAVRIC-SL IR images were statistically significant (all P<0.001). Pairwise comparison analysis suggested that the metal implant artifact area and the number of artifact-influence slices in the MAVRIC-SL IR image were smaller, and the SNR was higher than those of FS-T 2WI and PDWI (all P<0.05 after correction). The differences of the three scores among FS-T 2WI, PDWI and MAVRIC-SL IR were statistically significant (all P<0.001). Pairwise comparison analysis suggested that the degree of image artifacts score of MAVRIC-SL IR sequence was lower, and the measurability and other degree of artifacts scores were higher than FS-T 2WI and PDWI (all P<0.05 after correction). Conclusion:MAVRIC-SL can significantly reduce the metal artifacts and improve image quality in the postoperative MRI review of the patients with metal-fixed ACLR. Therefore, oblique sagittal MAVRIC-SL IR sequence can be used for assisting the diagnosis of conventional FS-T 2WI and PDWI.

Objective To learn the needs of family physicians for tertiary hospital support in the hierarchical medical system. Methods In July 2017 cluster sampling was made to 135 family physicians of Changning district of Shanghai for a " Family physicians needs questionnaire" . It covered such aspects as their demographic characteristics and their needs. The data so acquired were subject to descriptive and logical analysis. Results 99.3% of them need preferential appointment of specialists at tertiary hospitals;93.3% of them need preferential appointment of examinations; 82.2% of them need preferential outpatient visits; while 83.7% of them need preferential hospitalization and surgery scheduling. In terms of the approaches for preferential appointment of specialists, 84.4% of them prefer specialist appointment at short notice, and 73.3% of them need direct online appointment for large-scale device examinations at tertiary hospitals. In terms of mentoring scenarios, 62.2% of them prefer mentoring during outpatient rounds at fixed schedules of specialists in their community. Conclusions Tertiary hospitals are recommended to establish green pathways for referrals and priority measures in order to improve capabilities of family physicians and the shared platform in the hierarchical medical network. They are also expected to guide family physicians in their research paper writing, thus fully supporting the hierarchical medical system.