Acceptance and willingness to pay for DTaP-HBV-IPV-Hib hexavalent vaccine among parents: A cross-sectional survey in China.

DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease. Currently, no hexavalent vaccines have been approved for use in China. Evidence of parental acceptance and interest in hexavalent vaccines can help policy makers and manufacturers make decisions about entering the vaccine market and the immunization program in China. We measured parental acceptance and willingness-to-pay (WTP) for a hexavalent vaccine to provide such evidence. We conducted a cross-sectional survey of children's caregivers in 16 vaccination clinics in seven cities in China and obtained information on socio-demographics, knowledge of disease, confidence in vaccines, previous vaccination experience, and acceptance of and WTP for hexavalent vaccine. Multivariate logistic regression was used to determine factors influencing acceptance, and multivariate tobit regression was used to identify factors impacting WTP. Between April 28 and June 30, 2023, a total of 581 parents of children aged 0-6 years participated in the survey; 435 (74.87%, 95% CI:71.3%-78.4%) parents indicated acceptance of hexavalent vaccine. Residence location, parents' education level, experience paying for vaccination, and disease knowledge scores were key factors affecting parents' choices for vaccination. Mean (SD) and median (IQR) willingness to pay for full 4-dose course vaccination were 2266.66 (1177.1) CNY and 2400 (1600-2800) CNY. Children's age (p < .001), parents' education level (p = .024), and perceived price barriers (p < .001) were significantly associated with WTP. Parents have high acceptance and willingness to pay for hexavalent vaccine. The less money parents have to pay out of pocket, the more willing they can be to accept the vaccine. Therefore, acceptance may increase even further if the vaccine is covered by medical insurance, provided free of charge by the government, or if its price is reduced. Our results provide reference for optimizing and adjusting immunization strategies in China.

Recombinant Human Thrombopoietin Promotes Platelet Engraftment in Severe Aplastic Anemia Patients Following Treatment With Haploid Hematopoietic Stem Cell Transplantation using Modified Post-Transplantation Cyclophosphamide.

BACKGROUND: Recombinant human TPO (rhTPO) promotes platelet engraftment in patients after allogeneic HSCT (allo-HSCT). However, the effects of rhTPO on platelet recovery after Haplo-HSCT in patients with severe aplastic anemia (SAA) have not been intensively studied. OBJECTIVE: We aimed to evaluate the efficacy of rhTPO on platelet engraftment in patients with SAA who were treated with Haplo-HSCT using post-transplantation cyclophosphamide (PTCy). STUDY DESIGN: SAA patients who received Haplo-HSCT plus PTCy regimen were divided into the rhTPO group (with subcutaneous injection of rhTPO, n = 28) and Control group (no rhTPO administration, n = 27). The engraftment of platelet/neutrophil, platelet infusion amount, and transplant-related complications between the 2 groups were compared. RESULTS: All 55 patients showed successful hematopoietic reconstitution. The median time of platelet engraftment was 11 (9 to 29) days in the rhTPO group and 14 (9 to 28) days in the Control group (P = .003). The rhTPO group had a significantly reduced amount of infused platelets compared to the Control group (2 (1 to 11.5) versus 3 (1 to 14) therapeutic doses; P = .004). There was no significant difference between the 2 groups regarding median time of neutrophil engraftment, incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), incidence of cytomegalovirus or Epstein-Barr virus reactivation, 3-yr overall survival rate, and failure-free-survival rate. No obvious adverse reactions were observed in the rhTPO group. CONCLUSION: rhTPO promoted platelet engraftment, reduced the amount of transfused platelets, and demonstrated good safety profiles without evidence of adverse reactions in patients with SAA who received Haplo-HSCT using PTCy regimen.

The predictive value of BTG1 for the response of newly diagnosed acute myeloid leukemia to decitabine.

BACKGROUND: Decitabine has been widely used to treat acute myeloid leukemia (AML); however as AML is a heterogeneous disease, not all patients benefit from decitabine. This study aimed to identify markers for predicting the response to decitabine. METHODS: An intersection of in vitro experiments and bioinformatics was performed using a combination of epigenetic and transcriptomic analysis. A tumor-suppressor gene associated with methylation and the response to decitabine was screened. Then the sensitivity and specificity of this marker in predicting the response to decitabine was confirmed in 54 samples from newly diagnosed AML patients treated with decitabine plus IA regimen in a clinical trial (ChiCTR2000037928). RESULTS: In vitro experiments showed that decitabine caused hypomethylation and upregulation of BTG1, while downregulation of BTG1 attenuated the inhibitory effect of decitabine. In newly diagnosed AML patients who received decitabine plus IA regimen, the predictive value of BTG1 to predict complete remission (CR) was assigned with a sensitivity of 86.7% and a specificity of 100.0% when BTG1 expression was < 0.292 (determined using real-time quantitative PCR), with area under the curve (AUC) = 0.933, P = 0.021. The predictive value of BTG1 to predict measurable residual disease (MRD) negativity was assigned with a sensitivity of 100.0% and a specificity of 80.0% when BTG1 expression was < 0.292 (AUC = 0.892, P = 0.012). Patients were divided into low and high BTG1 expression groups according to a cutoff of 0.292, and the CR rate of the low-expression group was significantly higher than that of the high-expression group (97.5% vs. 50%, P < 0.001). CONCLUSIONS: Low expression of BTG1 was associated with CR and MRD negativity in newly diagnosed AML patients treated with a decitabine-containing regimen, suggesting that BTG1 is a potential marker for predicting the response to decitabine in newly diagnosed AML. CLINICAL TRIAL REGISTRATION: ChiCTR2000037928.

Upper gastrointestinal tract immune-related adverse events: Two cases of obstructive complications occurred in immune consolidation therapy after sequential chimeric antigen receptor T cell therapy with autologous hematopoietic stem cell transplantation for refractory/relapsed diffuse large B cell lymphoma.

Key Clinical Message: Immune checkpoint inhibitors are a very popular method of treating malignant tumors. But its side effects cannot be ignored. This study revealed obstructive complications during immune consolidation therapy following sequential chimeric antigen receptor T cell therapy with autologous hematopoietic stem cell transplantation in two patients with diffuse large b cell lymphoma (DLBCL). Both our patients had the same symptoms of vomiting and inability to eat due to pyloric obstruction, it should be highlighted that this is a relatively rare and irreversible complication of upper gastrointestinal caused by immune consolidation therapy. Abstract: Immune checkpoint inhibitors (ICIs) have become the standard therapy for many malignant tumors.However, ICIs are associated with unique immune-related adverse events (irAEs) caused by dysregulated immune activation and associated complications have been observed in patients. Here, we report two cases of patients with pyloric obstruction and duodenal ulcers induced by the use of sintilimab, which provides some guidance for the widely used anti-programmed death-1 therapy. During the entire treatment progression for such patients, the correct differential diagnosis of adverse effects and the use of immunosuppressive agents such as glucocorticoids are essential to facilitate early prevention and intervention of irAEs.

An Observational Prospective Cohort Study of Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection of an Aerosolized, Inhaled Adenovirus Type 5-Vectored Coronavirus Disease 2019 Vaccine Given as a Second Booster Dose in Guangzhou City, China.

Using a prospective, observational cohort study during the post-"dynamic COVID-zero" wave in China, we estimated short-term relative effectiveness against Omicron BA.5 infection of inhaled aerosolized adenovirus type 5-vectored ancestral strain coronavirus disease 2019 (COVID-19) vaccine as a second booster dose approximately 1 year after homologous boosted primary series of inactivated COVID-19 vaccine compared with no second booster. Participants reported nucleic acid or antigen test results weekly until they tested positive or completed predesignated follow-up. After excluding participants infected <14 days after study entry, relative effectiveness among the 6576 participants was 61% in 18- to 59-year-olds and 38% in ≥60-year-olds and was sustained for 12 weeks.

Peripheral Blood Smears Distinguish Infective Fever after CAR-T Therapy.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy carries the risk of inducing severe and life-threatening toxicities such as cytokine release syndrome (CRS), neurotoxicity, and infection. Although CRS and infections have similar symptoms, their treatment strategies differ, and early diagnosis is very important. For CRS and infections, the fastest detection time currently takes more than 24 h, so a quick and simple method to identify a fever after CAR T-cell infusion is urgently needed. METHODS: We enrolled 27 patients with recurrent fever treated with different types of CAR T-cells, including cluster of differentiation (CD) 7, CD19, CD22, and CD19-CD22 bicistronic CAR T-cells, and evaluated the infection events occurring in these patients. We detailed the morphology of CAR T-cells in peripheral blood smears (PBS) and reported the infection events, CAR transgene copy number, and inflammatory indicators within the first month after treatment. RESULTS: Similar morphological characteristics were observed in the PBS of different CAR T-cells, namely, enlarged cell bodies, deep outside and shallow inside basophilic blue cytoplasm, and natural killer (NK) cell-like purplish red granules. There were ten infections in nine of the twenty-seven patients (33%). The percentage of atypical lymphocytes in PBS was significantly associated with CAR transgene copy number and absolute lymphocyte count in all patients. The atypical lymphocyte percentage was significantly higher in the non-infection group. CONCLUSIONS: In conclusion, the unique morphology of CAR T-cells in PBS can be used to evaluate CAR T-cell kinetics and provide reliable evidence for the rapid early identification of fever after CAR T-cell infusion. CLINICAL TRIAL REGISTRATIONS: ChiCTR-OPN-16008526; ChiCTR-OPN-16009847; ChiCTR2000038641; NCT05618041; NCT05388695.

The APC/C E3 ligase subunit ANAPC11 mediates FOXO3 protein degradation to promote cell proliferation and lymph node metastasis in urothelial bladder cancer.

Urothelial bladder cancer (UBC) is one of the most prevalent malignancies worldwide, with striking tumor heterogeneity. Elucidating the molecular mechanisms that can be exploited for the treatment of aggressive UBC is a particularly relevant goal. Protein ubiquitination is a critical post-translational modification (PTM) that mediates the degradation of target protein via the proteasome. However, the roles of aberrant protein ubiquitination in UBC development and the underlying mechanisms by which it drives tumor progression remain unclear. In this study, taking advantage of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) 9 technology, we identified the ubiquitin E3 ligase ANAPC11, a critical subunit of the anaphase-promoting complex/cyclosome (APC/C), as a potential oncogenic molecule in UBC cells. Our clinical analysis showed that elevated expression of ANAPC11 was significantly correlated with high T stage, positive lymph node (LN) metastasis, and poor outcomes in UBC patients. By employing a series of in vitro experiments, we demonstrated that ANAPC11 enhanced the proliferation and invasiveness of UBC cells, while knockout of ANAPC11 inhibited the growth and LN metastasis of UBC cells in vivo. By conducting immunoprecipitation coupled with mass spectrometry, we confirmed that ANAPC11 increased the ubiquitination level of the Forkhead transcription factor FOXO3. The resulting decrease in FOXO3 protein stability led to the downregulation of the cell cycle regulator p21 and decreased expression of GULP1, a downstream effector of androgen receptor signaling. Taken together, these findings indicated that ANAPC11 plays an oncogenic role in UBC by modulating FOXO3 protein degradation. The ANAPC11-FOXO3 regulatory axis might serve as a novel therapeutic target for UBC.

Epidemiology and survival of primary extraosseous plasmacytoma: insights from a population-based study with a 20-year follow-up.

Primary extraosseous plasmacytoma (PEP) is a rare and localized form of plasmacytoma that is not well understood. This study aimed to investigate the clinical features and prognostic factors associated with PEP. Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 1044 patients diagnosed with PEP between 2000 and 2019 were identified. The average age was 60.3 ± 15.2 years, with 64.3% being male (male: female = 1.8:1) and 53.8% being over 60-year old. The survival outcome of patients with PEP depends on several factors including age, race, marital status, and treatment options such as chemotherapy, radiotherapy, and surgery, which were also identified as independent predictors of overall survival for PEP. Patients who were younger, Asian or Pacific Islander, American Indian or Native American, and received radiotherapy or surgery had a more favorable prognosis, while those who underwent chemotherapy had poorer outcomes.

Efficacy of genotypic susceptibility-guided tailored therapy for Helicobacter pylori infection: A systematic review and single arm meta-analysis.

BACKGROUND AND AIM: The prevalence of antibiotic resistance for Helicobacter pylori (H. pylori) has been increasing over the year, making it more difficult for traditional empirical therapy to successfully eradicate H. pylori. Thus, tailored therapy (TT) guided by molecular-based antibiotic susceptibility testing (AST) has been frequently recommended. We conducted a single-arm meta-analysis to determine the efficacy of tailored therapy guided by molecular-based AST. METHODS: A systematic literature review was performed on multiple databases, and studies on molecular-based TT were included. The eradication rates of TT by intention-to-treat (ITT) and per-protocol (PP) analyses were pooled respectively. RESULTS: A total of 35 studies from 31 literature (4626 patients) were included in the single-arm meta-analysis. Overall, the pooled eradication rate of TT was 86.9% (95% CI:84.7%-89.1%) by the ITT analysis, and 91.5% (95% CI:89.8%-93.2%) by PP analysis. The pooled eradication rates of first-line TT and rescue TT were 86.6% and 85.1% by ITT analysis and 92.0% and 87.9% by PP analysis, respectively. When tailored rescue therapy was based on the genotypic resistance to at least four antibiotics, the pooled eradication rates reached 89.4% by ITT analysis and 92.1% by PP analysis. For genotype-susceptive strains, the pooled eradication rate of TT with targeted antibiotics was 93.1% (95% CI:91.3%-94.9%), among which the pooled eradication rate of tailored bismuth quadruple therapy was the highest (94.3%). Besides, the eradication rate of 7-day TT or tailored triple therapy without bismuth for genotype-susceptive strains could both reach more than 93.0%. CONCLUSION: Tailored therapy guided by molecular-based AST can achieve somewhat ideal therapeutic outcomes. TT with a 7-day duration or without bismuth for genotype-susceptible strains can achieve good eradication efficacy. The effectiveness of TT can be improved to some extent by expanding the coverage of AST or by adding bismuth.

LncRNA MIR4435-2HG drives cancer progression by modulating cell cycle regulators and mTOR signaling in stroma-enriched subtypes of urothelial carcinoma of the bladder.

BACKGROUND: The risk for recurrence and metastasis after treatment for urothelial carcinoma of the bladder (UCB) is high. Therefore, identifying efficient prognostic markers and novel therapeutic targets is urgently needed. Several long noncoding RNAs (lncRNAs) have been reported to be correlated with UCB progression. In this study, we found that the subtype-specific lncRNA MIR4435-2 host gene (MIR4435-2HG) plays a novel oncogenic role in UCB. METHODS: RNA-Seq data of TCGA/BLCA were analyzed. The expression of MIR4435-2HG was measured by qRT-PCR in 16 pairs of bladder cancer tissues and adjacent normal tissues. The clinical relecance of MIR4435-2HG was validated via in situ hybridization performed on an in-house cohort of 116 UCB patient samples. RNA pull-down followed by mass spectrometry was performed to identify MIR4435-2HG-binding proteins. To identify signaling pathways involved in MIR4435-2HG activity, comprehensive in vitro and in vivo studies and RNA-Seq assays were performed using UCB cells in which MIR4435-2HG expression was knocked down or exogenously overexpressed. In addition, we performed RNA immunoprecipitation and Western blot analyses to validate the identified MIR4435-2HG-binding proteins and to determine the molecular mechanisms by which MIR4435-2HG promotes UCB progression. RESULTS: We found that MIR4435-2HG was significantly upregulated in the stromal-enriched subtype of UCB. Increased MIR4435-2HG expression was positively correlated with a high histological grade, advanced T stages, larger tumors, lymph node metastasis and a poor prognosis. In vitro experiments revealed that MIR4435-2HG expression silencing suppressed cell proliferation and induced apoptosis. Inhibition of MIR4434-2HG delayed xenograft tumor growth, while MIR4435-2HG overexpression reversed the MIR4435-2HG silencing-induced inhibition of UCB tumor phenotype acquisition. Mechanistically, we found that MIR4435-2HG positively regulated the expression of a variety of cell cycle regulators, including BRCA2 and CCND1. Knocking down MIR4435-2HG increased the sensitivity of tumor cells to the VEGFR inhibitor cediranib. Furthermore, we found that MIR4435-2HG regulated mTOR signaling and epithelial-mesenchymal transition (EMT) signaling pathways by modulating the phosphorylation of mTOR, 70S6K and 4EBP1. Finally, we confirmed that MIR4435-2HG enhances tumor metastasis through regulation of the EMT pathway. CONCLUSIONS: Our data indicate that upregulated MIR4435-2HG expression levels are significantly correlated with a poor prognosis of UCB patients. MIR4435-2HG promotes bladder cancer progression, mediates cell cycle (de)regulation and modulates mTOR signaling. MIR4435-2HG is an oncogenic lncRNA in UCB that may serve as a diagnostic and therapeutic target.

Comparison of haploidentical-allogeneic hematopoietic stem cell transplantation and intensive immunosuppressive therapy for patients with severe aplastic anemia with an absolute neutrophil count of zero: a retrospective study.

A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical-allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0% vs. 40.0%, P = 0.001; 80.0% vs. 17.1%, P = 0.001). With a median follow-up of 18.5 months (4.3~30.8 months), patients in the HID-HSCT group had longer overall survival and event-free survival (80.0% vs. 47.9%, P = 0.0419; 79.2% vs. 33.5%, P = 0.0048). These data suggested that HID-HSCT might be an effective alternative treatment option for adult patients with SAA with an ANC of zero, which requires further validation in an additional prospective study.

Primary blastic plasmacytoid dendritic cell neoplasm: a US population-based study.

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and poorly understood hematopoietic malignancy. This study aimed to investigate the clinical characteristics and prognostic factors in patients with primary BPDCN. Methods: Patients diagnosed with primary BPDCN from 2001 to 2019 were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Survival outcome was analysed with Kaplan-Meier method. Prognostic factors were evaluated based on the univariate and multivariate accelerated failure time (AFT) regression analysis. Results: A total of 340 primary BPDCN patients were included in this study. The average age was 53.7 ± 19.4 years, with 71.5% being male. The mostly affected sites were lymph nodes (31.8%). Most patients (82.1%) received chemotherapy, while 14.7% received radiation therapy. For all the patients, the 1-year, 3-year, 5-year, and 10-year overall survival (OS) were 68.7%, 49.8%, 43.9%, and 39.2%, respectively, and the corresponding disease-specific survival (DSS) were 73.6%, 56.0%, 50.2%, and 48.1%, respectively. Univariate AFT analysis showed that older age, marital status of divorced, widowed and separated at diagnosis, primary BPDCN only, treatment delay for 3-6 months and without radiation therapy were significantly associated with poor prognosis of primary BPDCN patients. But multivariate AFT analysis indicated that older age was independently associated with worse survival, while second primary malignancies (SPMs) and radiation therapy were independently associated with extended survival. Conclusions: Primary BPDCN is a rare disease with poor prognosis. Advanced age was linked independently to poorer survival, while SPMs and radiation therapy were linked independently to prolonged survival.

Real-World Effectiveness of Primary Series and Booster Doses of Inactivated Coronavirus Disease 2019 Vaccine Against Omicron BA.2 Variant Infection in China: A Retrospective Cohort Study.

BACKGROUND: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. METHODS: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. RESULTS: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. CONCLUSIONS: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.

NP and 9311 are excellent population parents for screening QTLs of potassium-efficient rice.

High and stable rice yields are critical to global food security, and potassium-deficient soils in East Asia have seriously limited rice production in the regions. It is feasible to screen potassium efficient quantitative trait locus(QTLs) from existing rice varieties to cope with rice production in potassium-deficient areas, and the selection of population parents is the key to locating major QTLs. After a long period of natural selection, potassium efficient rice varieties mainly exist in the region where the soil potassium level is low. The present study chose the representative twelve high-yielding rice varieties in east Asia, firstly, to measure plant height, fresh sheath weight, and fresh blade weight under hydroponic conditions. Based on the difference and consistency of the three parameters, NP as low potassium tolerant, and 9311 as low potassium sensitive rice variety were screened. We further analyzed the relative values of the six parameters of NP and 9311 treated with a culture medium containing different potassium (K+) concentrations and showed that the two varieties significantly differed in multiple low potassium concentrations. Meanwhile, we calculated the coefficient of variation of twelve rice varieties and most of those parameters reached a maximum at 4 mg/L K+, indicating that this concentration was suitable for screening potassium-efficient rice. We also measured the potassium content and the potassium-related traits in NP and 9311 tissues, and found that NP and 9311 significantly differed in potassium translocation. These differences may be responsible for the long-distance transport of potassium from the root to the aboveground part. In conclusion, we identified a pair of parents with significant differences in potassium translocation, which can be used to locate the relevant QTLs with high potassium efficiency to cope with the crisis of soil potassium deficiency in East Asia.

Cladribine- and decitabine-containing conditioning regimen has a low post-transplant relapse rate in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome.

To reduce the risk of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT), there have been continuing efforts to optimize the conditioning regimens. Our study aimed to analyze the risk factors associated with the relapse of relapsed/refractory (R/R), high-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) post-transplant and the efficacy of a new conditioning regimen involving decitabine and cladribine. Clinical data of 125 patients with R/R AML, high-risk AML and high-risk MDS who underwent allo-HSCT were collected. In addition, 35 patients with R/R AML, high-risk AML and high-risk MDS received treatment with a new conditioning regimen including decitabine and cladribine. Cox regression analysis was used to identify risk factors associated with OS, RFS and relapse. Among 125 patients who underwent allo-HSCT, CR before allo-HSCT and matched sibling donors were independent protective factors for OS. DNMT3A abnormality was an independent risk factor for both relapse and RFS. Among 35 patients who received a new conditioning regimen containing decitabine and cladribine, only six patients relapsed and 1-year cumulative incidence of relapse was 11.7%. Moreover, this new regimen showed efficient MRD clearance early after allo-HSCT. The combined decitabine- and cladribine-based conditioning regimen showed a low relapse rate and a high survival without an increased incidence of GVHD or adverse effects and thus has potential for use in allo-HSCT for R/R AML, high-risk AML and high-risk MDS.

Association of vaccine policy with virus infection and awareness of hepatitis B in Fujian, China.

China has regulated its hepatitis B vaccination policy. However, data on the prevalence of hepatitis B virus (HBV) infection have not been updated since 2014. In addition, the impact of the policy on awareness of hepatitis B is limited, especially in Fujian Province where HBV infection is highly prevalent. We conducted a sero-epidemiological survey in five national monitoring counties to address these concerns. A total of 5,873 subjects were included and classified into four birth cohorts according to the policy time nodes (1981, 1992, and 2002). The HBsAg carrier rate for the general population was 8.6% (95% confidence interval [CI]: 7.9-9.3). Compared with those born before 1981, adjusted odds ratios (OR) for HBV infection were 0.51 (95% CI: 0.43-0.62), 0.10 (0.08-0.12), and 0.015 (0.01-0.023) among the 1981-1991, 1992-2001, and ≥2002 birth cohorts, respectively; while the OR was 1.26 (1.00-1.57), 0.39 (0.26-0.58), and 0.019 (0.006-0.06) for HBsAg carriage, respectively. Among the 4865 residents aged ≥15 years, hepatitis B awareness has been declining since the introduction of the hepatitis B vaccine into the immunization program (ß = -0.25, SE = 0.08, P = .001, and ß = -0.20, SE = 0.08, P = .017 for 1992-2001 and ≥2002 birth cohort, respectively). This decline was obvious for the initiation time of the first dose of the hepatitis B vaccine. Although the hepatitis B vaccination policies have helped reduce the infection, the awareness has declined. More measures on the target population are warranted to improve the public's awareness of hepatitis B vaccination in the context of great achievements.

Association between vaccine dose and risk of hepatitis B virus infection in Fujian Province, China.

The increased dose of hepatitis B vaccine has been adopted for newborns since 2013 in Fujian, China. However, little is known about the impact of this measure on hepatitis B virus (HBV) prevention. We used the seroepidemiological surveys conducted in 2014 and 2020 to address the concern. Compared with subjects who received a 5 µg hepatitis B vaccine, participants who took a 10 µg hepatitis B vaccine were associated with a lower risk of HBV infection (adjusted odds ratio [OR] 0.26, 95% confidence interval [CI]: 0.10-0.68) and a marginal reduction risk of anti-HBc positive (OR, 0.37; 95% CI: 0.13-1.08; P = .07), but not for HBsAg carrier risk. The relation between vaccine dose and risk of anti-HBc positive (OR, 0.20; 95% CI: 0.05-0.81) became slightly stronger and significant among children investigated in 2020 who probably received universal vaccination. No significant association was found for subjects whose mothers were positive for HBsAg. The current 10 µg hepatitis B vaccines for universal vaccination for newborns are reasonable and effective in HBV prevention. More measures should be taken to reduce the risk of HBsAg carriers for infants whose mothers are positive for HBsAg.

The diagnostic role of complete MICM-P in metastatic carcinoma of bone marrow (MCBM) presented with atypical symptoms: A 7-year retrospective study of 45 cases in a single center.

Metastatic carcinoma of bone marrow (MCBM) tends to present with atypical symptoms and can be easily misdiagnosed or miss diagnosed. This study was conducted to investigate the clinical-pathological and hematological characteristics of MCBM patients in order to develop strategies for early detection, staging, treatment selection and prognosis predicting. We retrospectively analyzed 45 patients with MCBM diagnosed by bone marrow biopsy in our hospital during the past 7 years. The clinical symptoms, hemogram and myelogram features, Hematoxylin and eosin staining and immunohistochemistry staining of bone marrow biopsies, location of primary carcinoma and corresponding treatment of the 45 MCBM patients were analyzed in this study. In total, 35 (77.9%) of all patients presented pains including bone pain (73.3%) as the main manifestation, and 37 (82.2%) patients had anemia. Metastatic cancer cells were found in only 22 patients (48.9%) upon bone marrow smear examination, but in all 45 patients by bone marrow biopsy. The bone marrow of 18 (40.0%) patients was dry extraction. Distribution of metastatic carcinoma was diffuse in 20 (44.4%) patients and multi-focal in 25 (55.6%) patients, complicated with myelofibrosis in 34 (75.6%) patients. For bone marrow biopsy immunohistochemistry, 97.8% of the patients were CD45-negative, while 75.6% of the patients were Cytokeratin-positive. There were 30 patients (66.7%) identified with primary malignancies. The overall survival (OS) of 1 year for MCBM patients was 6.7%. There was a trend that patients with cancer of known primary obtained better prognosis according to the survival curve, but the finding was not statistically significant with Log-rank P = .160. Complete MICM-P plays a significant role in early diagnosis of MCBM. Bone marrow biopsy combined with immunohistochemistry is an underappreciated method for the diagnosis of MCBM, which should be taken as part of regular tests as well as bone marrow smear. Understanding the clinical-pathological and hematological characteristics of MCBM and conducting bone marrow biopsy in time are of great significance for early detection and treatment selection.

Prevalence and prognosis of hard-to-heal wounds with comorbidities in China.

OBJECTIVE: Regular retrospective analysis is necessary for potential improvement in clinical practice for the treatment of hard-to-heal wounds. Comorbidities and outcomes have demonstrated spatial and temporal diversity, emphasising the importance of updates in epidemiology. The complexity of healing hard-to-heal wounds has long been known, and so we sought evidence-based improvement on the current principles of treatment. METHOD: Demographic and clinical information of patients from the WoundCareLog database was collected. Patients who met the inclusion criteria and completed follow-up after treatment were included. Comorbidities were diagnosed and classified into eight categories based on ICD-10. We compared the demographic and aetiological characteristics between patients with and without comorbidities by t-test and Chi-squared test. The impact of comorbidities on wound healing were evaluated with a multivariate Cox model. RESULTS: A total of 2163 patients met the inclusion criteria and were enrolled, of whom 37.0% were aged 61-80 years, 36.0% were aged 41-60 years and 60.8% were male. The lower extremities and buttocks were the most commonly affected areas with hard-to-heal wounds. Non-traumatic wounds accounted for 66.6% of cases, and infection, pressure and diabetes were the most common causes. Paralysis and diabetes were the most important factors which led to a prolonged healing process and inferior clinical outcomes. CONCLUSION: Comorbidities of hard-to-heal wounds were treated as separate contributors and their weighted effect on outcome was calculated through correlation analysis. Paralysis and diabetes were the most unfavourable comorbidities affecting the treatment of non-traumatic hard-to-heal wounds. Our study highlighted the priority of comorbidity treatment through data-driven approaches. It provides potential value in developing better public health strategies and preventive medicine.

Somatic embryogenesis of Arabica coffee in temporary immersion culture: Advances, limitations, and perspectives for mass propagation of selected genotypes.

Culture in temporary immersion systems (TIS) is a valuable tool for the semi-automation of high frequency somatic embryogenesis of coffee. This system allows the intermittent exposure of explants to liquid medium in cycles of specific frequency and duration of immersion with renewal of the culture atmosphere in each cycle. TIS have revolutionized somatic embryogenesis of coffee plants as an alternative for scaling up and reducing costs associated with labor-intensive solid media culture. In Central America, somatic embryogenesis is employed on a commercial scale to produce F1 Coffea arabica hybrids. In Asia and Africa, somatic embryogenesis is used for the multiplication of selected genotypes of C. arabica and C.canephora. Somatic embryogenesis of coffee plants is considered a model system for woody species due to its biological versatility and low frequency of somaclonal variation. Nevertheless, the success of somatic embryogenesis for mass propagation of coffee plants depends on the development, optimization, and transfer of complementary technologies. Temporary immersion using the RITA® bioreactor is, so far, the best complementary tool for somatic embryogenesis of Arabica coffee for a single recipient with simple changes in liquid media. Likewise, high volume bioreactors, such as 10-L glass BIT® and 10-L flexible disposable plastic bags, have been successfully used for somatic embryogenesis of other coffee species. These bioreactors allow the manipulation of thousands of embryos under semi-automated conditions. The protocols, advantages, and benefits of this technology have been well documented for organogenesis and somatic embryogenesis pathways. However, adaptation in commercial laboratories requires technical and logistical adjustments based on the biological response of the cultures as well as the costs of implementation and production. This review presents the historical and present background of TIS and its commercial application and, in particular, pertinent information regarding temporary immersion culture for C. arabica somatic embryogenesis. The main limitations of this technology, such as hyperhydricity, asynchrony, and developmental abnormalities, are examined, and a critical analysis of current knowledge regarding physiological, biochemical, and molecular aspects of the plant response to temporary immersion is offered. Further, perspectives are provided for understanding and solving the morpho-physiological problems associated with temporary immersion culture of coffee plants. Systematic Review Registration.