Objective:To explore the experience of self-management dilemma ofadults with emerging ankylosing spondylitis, and to provide reference for the construction of self-management intervention strategies for emerging adults with ankylosing spondylitis.Methods:Descriptive phenomenology was used to conduct in-depth interviews with 14 adults with emerging ankylosing spondylitis in the Rheumatology and Immunology Department of Drum Tower Hospital Affiliated to Medical College of Nanjing University from August 2022 to March 2023. The interview data were analyzed by Colaizzi′s seven-step analysis method.Results:A total of 14 patients completed the interview,10 males, 4 females, aged 21-30 years. In adults with emerging ankylosing spondylitis, there were dilemmas of role maladjustment and disease management disorder, including role maladjustment of disease management and social role maladjustment. Barriers to disease management included weak self-management awareness, insufficient support for self-management information, inadequate self-management skills, and poor compliance with self-management behaviors.Conclusions:The role adaptation and self-management ability of adults with emerging ankylosing spondylitis are seriously inadequate. It is urgent to construct health management strategies for adults with emerging ankylosing spondylitis to help them improve the level of role adaptation and disease management.

Objective:To investigate the effect of subacute exposure of Di(2-ethylhexyl)phthalate(DEHP)on endometrial decidualization and early pregnancy miscarriage in mice.Methods:CD1 mice were orally administrated with 300(low-dose group),1000(medium-dose group),or 3000 mg·kg-1·d-1 DEHP(1/10 LD50,high-dose group)for 28 days,respectively.An early natural pregnancy model and an artificially induced decidualization model were established.The uterine tissues were collected on D7 of natural pregnancy and D8 of artificially induced decidualization,respectively.The effects of a subacute exposure to DEHP on the decidualization of mice were detected by HE staining,Masson staining,TUNEL assay,and Western blotting.A model of spontaneous abortion was constructed in mice after subacute exposure to 300 mg·kg-1·d-1 DEHP,and the effect of impaired decidualization on pregnancy was investigated by observing the pregnancy outcome on the 10th day of gestation.Results:Compared with the control group,the conception rate was significantly decreased in the high-dose DEHP subacute exposure group(P＜0.05).HE staining showed that,compared with the control group,the decidual stromal cells in the low-and medium-dose exposure groups were disorganized,the nuclei of the cells were irregular,the cytoplasmic staining was uneven,and the number of polymorphonuclear cells was significantly reduced.Masson staining showed that compared with the control group,the collagen fibers in the decidua region of the DEHP low-dose group and the medium-dose group were more distributed,more abundant and more disorderly.TUNEL assay showed increased apoptosis in the decidua area compared to the control group.Western blotting showed that the expression of BMP2,a marker molecule for endometrial decidualization,was significantly reduced(P＜0.05 or P＜0.01).The abortion rate and embryo resorption rate were increased,and the number of embryos,uterine wet weight,uterine area and placenta wet weight were decreased in DEHP low-dose group compared to the control group stimulated by mifepristone,an abortifacient drug(P＜0.05 or P＜0.01).Conclusion:Subacute exposure to DEHP leads to impaired endometrial decidualization during early pregnancy and exacerbates the risk of adverse pregnancy outcomes in mice.

Gut dysbiosis,a well-known risk factor to triggers the progression of Alzheimer's disease(AD),is strongly associated with metabolic disturbance.Trimethylamine N-oxide(TMAO),produced in the dietary choline metabolism,has been found to accelerate neurodegeneration in AD pathology.In this study,the cognitive function and gut microbiota of TgCRND8(Tg)mice of different ages were evaluated by Morris water maze task(MWMT)and 16S rRNA sequencing,respectively.Young pseudo germ-free(PGF)Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type(WT)mice were selected to determine the role of the gut microbiota in the process of neuropathology.Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions.Our results showed that gut dysbiosis,neuroinflammation response,Aβ deposition,tau hyper-phosphorylation,TMAO overproduction and cyclin-dependent kinase 5(CDK5)/transcription 3(STAT3)activation occurred in Tg mice age-dependently.Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice,with the activation of CDK5/STAT3 signaling in the brains.On the contrary,faecal microbiota transplantation from WT mice alleviated the cognitive deficits,attenuated neuro-inflammation,Aβ deposition,tau hyperphosphorylation,TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice.Moreover,excessive choline treatment was also shown to aggravate the cognitive deficits,Aβ deposition,neuroinflammation and CDK5/STAT3 pathway activation.These findings provide a novel insight into the interaction between gut dysbiosis and AD progression,clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.

Transcatheter arterial chemoembolization (TACE) is recommended by domestic and international guidelines for the treatment of patients with unresectable hepatocellular carcinoma (uHCC), and it is one of the most common treatment methods for patients with uHCC. The chemotherapy drugs commonly used in TACE for HCC include epirubicin, cisplatin, and fluorouracil, while it is still unclear which chemotherapy drug has a better clinical effect. This article summarizes the studies of different TACE regimens using different chemotherapy drugs in the treatment of patients with uHCC in the recent five years. TACE combined with sorafenib can significantly improve the survival of patients with advanced HCC and has been recommended for the treatment of such patients by Chinese Society of Clinical Oncology guidelines, and the efficacy of TACE combined with other tyrosine kinase inhibitors (TKI) has become a research hotspot. Studies have shown that compared with TACE combined with sorafenib in the treatment of patients with advanced HCC, TACE combined with lenvatinib can achieve a significantly longer progression-free survival time and a tendency of increase in median overall survival time. However, due to the variation of target receptors or downstream signals, resistance to molecular-targeted agents is still a challenging problem. TKI combined with immune checkpoint inhibitors may be a promising strategy for the treatment of patients with uHCC. Some studies suggest that triple therapy using TACE combined with TKIs and anti-PD-1/PD-L1 monoclonal antibody has better efficacy in improving the survival of patients with uHCC. This article reviews the studies of the efficacy and safety of TACE combined with targeted agents and TACE combined with anti-PD-1/PD-L1 monoclonal antibody in the treatment of patients with uHCC in the recent five years.

Humans ; Hearing Loss, Sudden/diagnosis* ; Tinnitus

Objective: To analyze the clinical characteristics of hepatic flare and evaluate efficacy of antiviral treatment in pregnant women with chronic HBV infection. Methods: A single-center, open-label, prospective study was conducted, and pregnant women with chronic HBV infection were enrolled. Liver function, HBV serum markers and HBV DNA of pregnant women with chronic HBV infection were reviewed during every 4 to 12 weeks of gestation period. The proportion and clinical characteristics of hepatitis flare during pregnancy were observed. Logistic regression analysis was used to predict hepatic flare in pregnant women with chronic HBV infection. Antiviral therapy with telbivudine (LdT) or tenofovir dipivoxil (TDF) was used to treat hepatic flare during pregnancy. Sequential entecavir (ETV) or TDF was applied after the delivery. Treatment course and drug withdrawal in pregnant women with hepatic flare was the same as those of the general patients with chronic hepatitis B. Liver function, HBV serum markers and HBV DNA were measured in pregnant women with hepatic flare at different time points (4, 12, 24 and 52 weeks). A t-test was used to compare the hepatic flare in pregnant women with and without hepatitis group. HBsAg and HBeAg were used to quantify the receiver operating characteristic (ROC) curve of pregnant women with hepatic flare during pregnancy. Area under the ROC curve was used to calculate the optimal cut-off value corresponding to the maximum sensitivity and specificity of the ROC curve. Results: Of the 220 pregnant women with chronic HBV infection, 55 (25%) had hepatitis flare during pregnancy and received antiviral treatment. Among the 55 women with hepatic flare during gestation, 47 (85.46%) had hepatic flare in the mid-second trimester (12-24 weeks); average peak value of alanine aminotransferase (ALT) was 220.62 U/L, and the average peak value of ALT in 32 cases (58.18%) of pregnant women with hepatic flare was between 2–5 × ULN. HBsAg and HBeAg quantification were significantly lower in pregnant women with hepatic flare during pregnancy than with non-hepatitis (t = -3.745, P < 0.001; t = -2.186, P = 0.030). Multivariate logistic regression analysis showed that pregnant women with HBeAg < 3.065 log10 s/co were 7.576 times more likely to have hepatic flare during pregnancy (95% confidence interval: 3.779-15.190). ALT normalization, undetectable HBV DNA levels, HBeAg loss and HBeAg seroconversion in 55 pregnant women with hepatic flare at 52-week treatment was 100% (55/55), 74.55% (41/55), 47.27% (26/55) and 41.82% (23/55), respectively. HBsAg quantification at 52 weeks was significantly lower than baseline HBsAg quantification (3.32 + 0.37) log₁₀ IU/ml and (3.95 + 0.40) log₁₀ IU/ml; t = 8.465, P < 0.001). Conclusion Hepatic flare often occurs in the second trimester of pregnancy in pregnant women with chronic HBV infection and baseline HBeAg quantification is an independent predictor of hepatic flare. HBeAg seroconversion rate increased at 52 weeks after antiviral therapy.

Knee osteoarthritis (KOA ) is a common chronic degenerative disease in the elderly population .It is character-ized by knee-joint pain ,swelling ,morning stiffness and seriously affects the patients′motor function and physical health .So far ,there is no early diagnosis and effective treatment for it .This paper outlined the recent researches on knee osteoarthritis and inflammatory cytokines to discuss the relationship between knee osteoarthritis and inflammatory factors such as IL-1β,IL-6 ,TNF-α,TGF-β,IL-10 ,IL-17 and IL-37 ,and provide the theoretical basis for the diagnosis and treatment of knee osteoar-thritis .

Objective:To observe the effect of tuina manipulations on blood pressure and its variability in hypertension patients. Methods:Forty hypertension patients were randomized into an observation group and a medication group, 20 cases in each group. The observation group was intervened by tuina manipulations of kidney-tonifying blood-circulating and collaterals- unblocking in addition to regular medication, while the medication group was by the same medication. The 24-hour blood pressure monitoring was performed before intervention and after 3-month intervention. The blood pressure and its variability were observed and compared. Results:There were no significant differences in comparing the blood pressure and blood pressure variability between the two groups before intervention (P>0.05); after 3-month intervention, the blood pressure and its variability were significantly improved in both groups (P<0.05); the improvements in the observation group were more significant than those in the control group (P<0.05). Conclusion:Tuina manipulations of kidney-tonifying blood-circulating and collaterals-unblocking plus medication can produce a better effect than regular medication in promoting blood pressure and its variability, and this method is worth applying in clinic as it’s easy-to-operate and has no adverse effect.

OBJECTIVE This study aimed at identifying inner ear malformation underlying molecular determinant(s) using a large five-generation Chinese family with multiple familial cases. METHODS Model-based genetic linkage analyses were performed with the use of microsatellite polymorphisms to determine the disease locus. Mutation screening was performed with the family and unrelated population-based controls to establish molecular evidence that caused the specific X-linked inheritance pattern in the family. RESULTS Clinical investigations of the pedigree demonstrated the extremely high penetrance in the male members, but no penetrance in the female members. Linkage analyses mapped the disease to the chromosomal region Xq13.1-Xq23 (maximum X-linkage LOD score = 3.27). Mutation screening of the candidate genes in the linkage region by direct sequencing revealed a de novo missense substitution (925T→C) in the well-known deaf gene POU3F4. Direct sequencing on 110 unrelated controls did not detect any mutation. CONCLUSION a novel mutation of POU3F4 gene was identified to be the causative reason for the hearing loss in family with inner ear malformation.

OBJECTIVE To investigate whether the KCNN4 gene and KPTN gene contribute to a Chinese non-syndromic hearing loss pedigree linked to DFNA4 with positional candidate approach. METHODS The complete coding region of the two genes were amplified with polymerase chain reaction (PCR), and bidirectional sequencing of the PCR products was subsequently applied in the 36 family members to identify the possible mutations or polymorphisms in the candidate genes. RESULTS Sequence analysis of coding regions and splice sites of the two candidate genes in 36 members including 12 hearing-impaired individuals in family Z002 failed to demonstrate any deafness-causing mutations of KCNN4 gene. There was one heterozygous mutation identified in exon10 coding sequence (942C/T) of KPTN gene, which did not result in amino acid change (P302P) as a repoerted synonymous SNP site (rs2293424). This SNP site did not cosegregate with the phenotype of family Z002. CONCLUSION Our study excluded the two candidates, KCNN4 and KPTN , as the causative genes involved in this Chinese DFNA4 pedigree.