Correlation analysis of IL-37 gene polymorphisms and susceptibility to chronic HBV infection among Han people in Central China.

Hepatitis B virus (HBV) is responsible for various liver diseases, such as chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis (LC) and hepatocellular carcinoma (HCC), which pose a significant threat to human health. An ineffective immune response to HBV can result in viral chronicity. Interleukin-37 (IL-37), an immunomodulator, is capable of inhibiting both innate and adaptive immune responses. It is believed that single nucleotide polymorphisms (SNPs) within the IL-37 gene could contribute to the regulation of HBV clearance. Our aim to conduct this study was to investigate whether SNPs in the IL-37 gene were associated with the risk of chronic HBV infection in adults. A total of 342 participants, consisting of 171 cases and 171 controls, were recruited for this study. Sanger sequencing was employed for genotyping six SNPs (rs3811042 G/A, rs3811043 G/C, rs2466449 A/G, rs3811045 C/T, rs3811046 T/G and rs3811047G/A). There was no significant difference in allele and genotype distribution between the two groups, and the constructed haplotypes were not found to be associated with the risk of chronic HBV infection. Our results revealed that there was no relationship between these six SNPs (rs3811042G/A, rs3811043G/C, rs2466449A/G, rs3811045C/T, rs3811046T/G and rs3811047G/A) in the IL-37 gene and susceptibility to chronic HBV infection among Han people in Central China.

Genetic diversity and functional implication of the long control region in human papillomavirus types 52, 58, and 16 from Central China.

OBJECT: High-risk human papillomavirus (HR-HPV) is a main reason for cervical cancer. The long control region (LCR) of the genome plays a variety of roles in the transcription of the virus. METHODS: LCR sequences were amplified by polymerase chain reaction (PCR) and confirmed by DNA sequencing. MEGA 11.0 software and NCBI blast were used to analyze the sequences and construct the Neighbor-Joining tree. In addition, the JASPAR database was used to predict the potential transcription factor binding sites (TFBS). RESULTS: For HPV-52 LCR, 68 single nucleotide polymorphisms (SNPs), 8 deletions, and 1 insertion were found, 17 of which were novel variations. Most of the variants were clustered in B2 sub-lineage (96.22%). For HPV-58 LCR, 25.43% of samples were prototype. 49 SNPs, 2 deletions, and 1 insertion were observed in the remaining samples. A1 sub-lineage was the most frequent (64.16%). For HPV-16 LCR, 75 SNPs and 2 deletions were identified, 13 of which were newly identified. A total of 55.68% of the variants were distributed in A4 sub-lineage. The JASPAR results suggested that multiple variations occurred in TFBSs, which might affect the function of transcription factors. CONCLUSIONS: This study provides experimental data for further studies on the epidemiology and biological function of LCR. Various LCR mutational data may prove useful for exploring the carcinogenic mechanism of HPV.

Association of TLR4 and TLR9 gene polymorphisms with cervical HR-HPV infection status in Chinese Han population.

BACKGROUND: Toll-like receptors (TLRs) may be involved in the natural history of human papillomavirus (HPV) infection. In our study, we aimed to investigate the association of TLR4 (rs10116253, rs1927911, rs10759931) and TLR9 (rs187084, rs352140) gene polymorphisms with cervical persistent high-risk HPV (HR-HPV) infection, as well as multiple HR-HPV infections. METHODS: A total of 269 study subjects were enrolled and grouped by retrospectively analyzing the HR-HPV testing results and other clinical data of 2647 gynecological outpatients from Jingzhou Hospital Affiliated to Yangtze University. We conducted a case-control study to compare the role of TLR4/TLR9 gene polymorphisms between HR-HPV transient and persistent infections, as well as between HR-HPV single and multiple infections. HR-HPV genotypes were detected using Real-time polymerase chain reaction (RT-PCR). PCR-restriction fragment length polymorphism (PCR-RFLP) was used to determine TLR4 and TLR9 gene polymorphisms. Analyses of the different outcome variables (HR-HPV infection status and time for HR-HPV clearance) with respect to TLR4/TLR9 polymorphisms were carried out. Logistic regression analysis was used to determine the association of TLR4/TLR9 genotypes and alleles with HR-HPV infection status. The Kaplan-Meier method with the log-rank test was used to analyze the relationship between TLR4/TLR9 genotypes and the time for HR-HPV clearance. RESULTS: The mutant genotypes of TLR9 rs187084 and rs352140 were associated with persistent (rs187084: CT and CT+CC; rs352140: CT and CT+TT) and multiple (rs187084: CT and CT+CC; rs352140: CT+TT) (all P < 0.05) HR-HPV infection. However, no association was found between TLR4 polymorphisms and HR-HPV infection status. Kaplan-Meier time to HR-HPV clearance analysis demonstrated that women carrying rs187084 and rs352140 mutant genotypes take longer duration to clear HR-HPV infection compared with wild-type genotype carriers (P1 = 0.012; P2 = 0.031). CONCLUSION: Our results suggested that TLR9 polymorphisms, but not TLR4, were associated with cervical persistent and multiple HR-HPV infections, which could be useful as a potential predictor of HR-HPV infection status.

Clinical characteristics and long-term management of prepubertal testicular teratomas: a retrospective, multicenter study.

Prepubertal testicular teratomas are rare tumors with limited practical guidance for their management. This study aimed to analyze a large multicenter database to establish the optimal management of testicular teratomas. We retrospectively collected data on testicular teratomas in children younger than 12 years who underwent surgery without postoperative chemotherapy in three large professional children's institutions in China between 2007 and 2021. The biological behavior and long-term outcomes of testicular teratomas were analyzed. In total, 487 children (with 393 mature teratomas and 94 immature teratomas) were included. Among mature teratomas, 375 cases were testis-sparing, 18 were orchiectomies, 346 were operated through the scrotal approach, and 47 underwent the inguinal approach. The median follow-up period was 70 months, and no recurrence or testicular atrophy was observed. Among the children with immature teratomas, 54 underwent testis-sparing surgery, 40 underwent orchiectomy, 43 were operated through the scrotal approach, and 51 were operated through the inguinal approach. Two cases of immature teratomas with cryptorchidism had local recurrence or metastasis within 1 year of the operation. The median follow-up duration was 76 months. No other patients had recurrence, metastasis, or testicular atrophy.  Conclusion: Testicular-sparing surgery is the first treatment choice for prepubertal testicular teratomas, with the scrotal approach being a safe and well-tolerated strategy for these diseases. Additionally, patients with immature teratomas and cryptorchidism may have tumor recurrence or metastasis after surgery. Therefore, these patients should be closely followed up in the first year after surgery. What is Known: • There is a fundamental difference between testicular tumours in childhood and those in adulthood - not only in terms of the difference and incidence but also in terms of histology. • For surgical techniques, the inguinal approach is recommended for the treatment of testicular teratomas in children. What is New: • The scrotal approach being a safe and well-tolerated strategy for testicular teratomas in children. • Patients with immature teratomas and cryptorchidism may have tumor recurrence or metastasis after surgery. These patients should be closely followed up in the first year after surgery.

Research progress on detection methods for hepatitis B virus covalently closed circular DNA.

Hepatitis B virus (HBV) infection remains a serious global public health problem, and HBV covalently closed circular DNA (cccDNA) in the nucleus of infected cells cannot be eliminated by current treatments and is a major factor in the persistence and recurrence of hepatitis B. Efficient and scientific detection methods are important for clinical monitoring of cccDNA and targeted drug development. Western blotting is the gold standard for the quantitative detection of cccDNA, but it is time-consuming and complex. In recent years, new detection technologies have been continuously updated. There are new developments and breakthroughs in both next-generation polymerase chain reaction (PCR) and non-PCR methods such as in situ hybridization. Some HBV-related markers (such as hepatitis B core-related antigen) have also been shown to be closely related to cccDNA, and they can be used as surrogate markers to indirectly reflect cccDNA content. In this paper, the main detection methods of cccDNA and their improvements are reviewed, the advantages and limitations of these methods are analysed and summarized, and future development directions are proposed.

Metabolic Characteristics of Gestational Diabetes Mellitus and the Effects on Pregnancy Outcomes.

Objective: To describe the metabolic characteristics of gestational diabetes mellitus (GDM) and assess their effects on perinatal outcomes. Methods: A two-center nested case‒control study was designed, including 192 pregnant women with GDM and 191 pregnant women with normal glucose tolerance (NGT). Serum glucose and insulin concentrations based upon the 75 g oral glucose tolerance test (OGTT) were measured. Several indices were calculated to describe the metabolic characteristics of the subjects. The relationship between glucose metabolism parameters and pregnancy outcomes was evaluated using stepwise linear regression and binary logistic regression. Results: Compared with the NGT group, the GDM group showed significantly higher fasting and postprandial glucose parameters but significantly lower fasting and postprandial insulin responses. Meanwhile, the GDM group had significantly lower HOMA-ß, DI and ISIMatsuda but comparable HOMA-IR. The IFG subgroup showed significantly lower FINS/FPG only, while the IGT and IFSG subgroups showed deficiency in both fasting and postprandial insulin response. The IFSG subgroup had the highest glucose parameters and the lowest insulin parameters, as well as significantly lower ISIMatsuda and HOMA-ß than the NGT group. FPG had a significant effect on infants' birth weight, and 1hPG and FINS/FPG had a significant effect on delivery gestational age. AUC-INS, IGI60 and DI were related to premature delivery risk after adjusting for confounders. The IFG subgroup of GDM was 2.319 times more likely to be subject to cesarean section than the NGT group. FPG, FINS/FPG, AUC-GLU, AUC-INS/AUC-GLU and HOMA-ß were related to macrosomia risk. Conclusion: Beta cell dysfunction rather than insulin resistance determines the occurrence of GDM in the central Chinese population. Women with predominant insulin secretion defects had a similar risk of adverse perinatal outcomes to women with NGT. Our study provided a basis for the selection of glucose metabolism monitoring indicators useful for the prevention of adverse perinatal outcomes.

Acceptance of seasonal influenza vaccination and associated factors among pregnant women in the context of COVID-19 pandemic in China: a multi-center cross-sectional study based on health belief model.

BACKGROUND: Seasonal influenza can circulate in parallel with coronavirus disease (COVID-19) in winter. In the context of COVID-19 pandemic, the risk of co-infection and the burden it poses on healthcare system calls for timely influenza vaccination among pregnant women, who are the priority population recommended for vaccination. We aimed to evaluate the acceptance of influenza vaccination and associated factors among pregnant women during COVID-19 pandemic, provide evidence to improve influenza vaccination among pregnant women, help reduce the risk of infection and alleviate the burden of healthcare system for co-infected patients. METHODS: We conducted a multi-center cross-sectional study among pregnant women in China. Sociodemographic characteristics, health status, knowledge on influenza, attitude towards vaccination, and health beliefs were collected. Locally weighted scatterplot smoothing regression analysis was used to evaluate the trends in the acceptance of influenza vaccine. Logistic regression was applied to identify factors associated with vaccination acceptance. RESULTS: The total acceptance rate was 76.5% (95%CI: 74.8-78.1%) among 2568 pregnant women enrolled. Only 8.3% of the participants had a history of seasonal influenza vaccination. In the logistic regression model, factors associated with the acceptance of influenza vaccine were western region, history of influenza vaccination, high knowledge of influenza infection and vaccination, high level of perceived susceptibility, perceived benefit, cues to action and low level of perceived barriers. Among 23.5% of the participants who had vaccine hesitancy, 48.0% of them were worried about side effect, 35.6% of them lacked confidence of vaccine safety. CONCLUSIONS: Our findings highlighted that tailored strategies and publicity for influenza vaccination in the context of COVID-19 pandemic are warranted to reduce pregnant women's concerns, improve their knowledge, expand vaccine uptake and alleviate pressure for healthcare system.

CC16-TNF-α negative feedback loop formed between Clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation.

CC16 is almost exclusively expressed in non-ciliated epithelial Clara cells, and widely used as a Clara cell marker. Diesel exhaust particles (DEPs), the fine particulate matters produced by diesel engines, cause or exacerbate airway-related diseases. Our previous study documented that DEP inhibits the CC16 expression in the immortalized mouse Clara cell line through methylation of C/EBPα promoter. However, the molecular mechanism by which DEP regulates CC16 secretion is unclear. Here, we isolated CC16 containing Clara cells (CC16+) from human distal lung, and found that DEP inhibited CC16 secretion from CC16+ cells via methylation of C/EBPα and inhibition of Munc18b transcription. CC16+ cell conditioned media containing different concentrations of CC16 was prepared and used for culture of airway epithelial cells BEAS-2B with no expression of CC16. A positive correlation was observed between CC16 level and DEP-induced autophagy activity, and a negative correlation between CC16 level and DEP-induced pro-inflammatory cytokine TNF-α, IL-6, and IL-8 level, suggesting that CC16 might mitigate DEP-induced inflammation via promoting autophagy in BEAS-2B cells. This result was further confirmed by adding recombinant CC16 to BEAS-2B cells exposed to DEP. Moreover, CC16 level was significantly increased when CC16+ cells were cultured in BEAS-2B cell conditioned medium containing TNF-α or the normal medium supplemented with recombinant TNF-α, suggesting that TNF-α induced CC16 production and secretion from CC16+ cells. Collectively, these data point that CC16 and TNF-α form a negative feedback loop, and this negative feedback loop between Clara cells and normal airway epithelial cells protects against DEP exposure-induced inflammation.

Acceptance of a COVID-19 vaccine and associated factors among pregnant women in China: a multi-center cross-sectional study based on health belief model.

Background: Vaccine hesitancy has been recognized as an urgent public health issue. We aimed to explore the acceptance of a COVID-19 vaccine and related factors among pregnant women, a vulnerable population for vaccine-preventable diseases.Methods: A multi-center cross-sectional study among pregnant women was conducted in five provinces of mainland China from November 13 to 27, 2020. We collected sociodemographic characteristics, attitude, knowledge, and health beliefs on COVID-19 vaccination. Locally weighted scatterplot smoothing regression analysis was used to assess the trends of vaccination acceptance. Multivariable logistic regression was performed to identify factors related to vaccination acceptance.Results: Among the 1392 pregnant women, the acceptance rate of a COVID-19 vaccine were 77.4% (95%CI 75.1-79.5%). In the multivariable regression model, the acceptance rate was associated with young age (aOR = 1.87, 95% CI: 1.20-2.93), western region (aOR = 2.73, 95% CI: 1.72-4.32), low level of education (aOR = 2.49, 95% CI: 1.13-5.51), late pregnancy (aOR = 1.49, 95% CI: 1.03-2.16), high knowledge score on COVID-19 (aOR = 1.05, 95% CI: 1.01-1.10), high level of perceived susceptibility (aOR = 2.18, 95% CI: 1.36-3.49), low level of perceived barriers (aOR = 4.76, 95% CI: 2.23-10.18), high level of perceived benefit (aOR = 2.18, 95% CI: 1.36-3.49), and high level of perceived cues to action (aOR = 15.70, 95% CI: 8.28-29.80).Conclusions: About one quarters of pregnant women have vaccine hesitancy. Our findings highlight that targeted and multipronged efforts are needed to build vaccine literacy and confidence to increase the acceptance of a COVID-19 vaccine during the COVID-19 pandemic, especially for vulnerable populations.

Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induces uncontrolled and self-amplified pulmonary inflammation, and has high morbidity and mortality rates in critically ill patients. In recent years, many bioactive ingredients extracted from herbs have been reported to effectively ameliorate ALI/ARDS via different mechanisms. Ferroptosis, categorized as regulated necrosis, is more immunogenic than apoptosis and contributes to the progression of ALI. In this study, we examined the impact of panaxydol (PX), isolated from the roots of Panax ginseng, on lipopolysaccharide (LPS)-induced ALI in mice. METHODS: In vivo, the role of PX on LPS-induced ALI in mice was tested by determination of LPS-induced pulmonary inflammation, pulmonary edema and ferroptosis. In vitro, BEAS-2B cells were used to investigate the molecular mechanisms by which PX functions via determination of inflammation, ferroptosis and their relationship. RESULTS: Administration of PX protected mice against LPS-induced ALI, including significantly ameliorated lung pathological changes, and decreased the extent of lung edema, inflammation, and ferroptosis. In vitro, PX inhibited LPS-induced ferroptosis and inflammation in bronchial epithelial cell line BEAS-2B cells. The relationship between ferroptosis and inflammation was investigated. The results showed that ferroptosis mediated inflammation in LPS-treated BEAS-2B cells, and PX might ameliorate LPS-induced inflammation via inhibiting ferroptosis. Meanwhile, PX could upregulate Keap1-Nrf2/HO-1 pathway, and selective inhibition of Keap1-Nrf2/HO-1 pathway significantly abolished the anti-ferroptotic and anti-inflammatory functions of PX in LPS-treated cells. CONCLUSION: PX attenuates ferroptosis against LPS-induced ALI via Keap1-Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for ALI.

Birt-Hogg-Dubé syndrome: a literature review and case study of a Chinese woman presenting a novel FLCN mutation.

BACKGROUND: The Birt-Hogg-Dubé (BHD) syndrome is a very rare autosomal dominant form of genodermatosis caused by germline mutations in the folliculin (FLCN) gene, which is mapped to the p11.2 region in chromosome 17. BHD commonly presents cutaneous fibrofolliculomas, pulmonary cysts, renal cell carcinoma, and recurrent pneumothoraxes. The disease is easily ignored or misdiagnosed as pneumothorax, pulmonary lymphangiomyomatosis (LAM), or emphysema. Follow-up and guidelines for managing recurrent pneumothoraxes in these patients are lacking. CASE PRESENTATION: We reported the case of a 56-year-old Chinese woman who presented skin lesions, multiple lung bubblae, recurrent pneumothoraxes, thyroid nodules, and pulmonary inflammatory pseudotumors (PITs). The patient had a family history of pneumothoraxes and renal tumor. The BHD diagnosis was confirmed by genetic testing, which revealed a novel FLCN mutation in exon 14. Furthermore, the patient underwent a bullectomy because of recurrent pneumothorax 6 years ago. CONCLUSION: To our knowledge, the novel mutation in exon 14 and the manifestation of PIT in the present case have never been reported for BHD. The patient underwent a bullectomy previously with no relapse at the last follow-up before the preparation of this report, thereby suggesting that thoracotomy with bullectomy may be a possible therapeutic approach for some BHD patients with recurrent pneumothorax.