Health economic analysis and medical cost analysis of children with severe hepatitis B in China: A retrospective study from 2016 to 2022.

BACKGROUND: Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China. METHODS: Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran's I  analysis. RESULTS: The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603,) of total cases and cirrhosis cases accounted for 11.23% (180/1603,). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (GDP, Moran's I <0) and percentage of urban population (Moran's I <0), and positively correlated with the number of pediatric beds per million population (Moran's I >0). CONCLUSION: The number of severe hepatitis B cases is low in areas with high GDP levels and high urban population ratios, and health care costs have been declining over the years.

Progress towards the Total Syntheses of Amaryllidaceae Alkaloids γ-Lycorane.

γ-Lycorane, a degradation product of the Aromaticaceae alkaloid lycorine, is one of the most attractive molecules in the Aromaticaceae family. It remains a popular target for synthesis due to its pentacyclic structure, which presents a vehicle for demonstrating the utility of new synthetic strategies. Various synthetic methods have been developed by synthetic chemists since the first synthesis of γ-lycorane by Nasuo in 1966. Thus, this review presents an overview of the literature on the ways utilized within the synthesis of γ-lycorane in racemic and enantiopure forms via electrophilic arylation, Pd-catalyzed C-C coupling, Bischler-Napieralski cyclization, Pictet-Spengler cyclization, photocyclization, radical cyclization, chiral pool synthesis, chiral auxiliary-mediated synthesis, and catalytic asymmetric synthesis, ranging from 1966 to 2022.

Influence of Plastic Deformation on Microstructural Evolution of 100Cr6 Bearing Ring in Hot Ring Rolling.

The hot ring rolling technology as the crucial procedure for the manufacture of bearing rings plays an important role in determining the final microstructure of bearing rings. In this work, the influence of the hot ring rolling process on the microstructural evolution of 100Cr6 bearing rings was investigated using a three-dimensional (3D) numerical model and microstructural characterization. It was found that the significant microstructural refinement occurs at the different regions of the rings. However, owing to the non-uniform plastic deformation of hot rolling, the refinement rate of grain size and decrease of pearlite lamellar spacing (PLS) also showed uniformity at different regions of the rings. Furthermore, the degree of grain refinement had been limited with the increase of rolling reduction. Due to the refined grain size and decreased PLS, the Vickers hardness increased with the increase of rolling reduction. Moreover, the Vickers hardness from the outer surface to the inner surface of the ring is asymmetrical u-shaped, which had the law of lower hardness in the center area and higher hardness on the surface.

Tumor length-to-height ratio as a predictor of recurrent laryngeal nerve lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma.

BACKGROUND: The metastasis of laryngeal nerve lymph node is mostly found in the upper-and middle esophageal cancer, the ratio of esophageal length from the upper incisors to the position where the esophageal tumor began to appear as proven via endoscopy to the height (LH) is likely to affect the possibility of detection of recurrent laryngeal nerve(RLN) lymph node (LN) metastasis. The purpose of this study was to evaluate the predictive value of LH for RLN LN metastasis. METHODS: One hundred and eighty-eight patients (mean age: 64.89 years; range: 46-84 years) calculated LH before esophagectomy and LN dissection were retrospective analyzed. The clinicopathological data of the patients, LH calculations were compared with the RLN LN histopathologic results to investigate the effect of LH on the diagnosis of RLN LN metastasis. RESULTS: The LH correlated with that of the RLN LN metastasis in receiver-operating-characteristic (ROC) analysis. Our ROC analyses demonstrated the optimal cut-off value was 16.66 for LH with an area under the curve value of 0.69. Compared with the Height (H) and L, ROC curve for LH have better performance in predicting the RLN LN metastasis. CONCLUSIONS: LH is a useful predictive tool in the evaluation of RLN LN metastasis for esophageal cancer. The present findings support the result that LH can be an indicator of RLN LN dissection.

Benefits of ultra-fast-track anesthesia for children with congenital heart disease undergoing cardiac surgery.

BACKGROUND: To compare the outcomes of ultra-fast-track anesthesia (UFTA) and conventional anesthesia in cardiac surgery for children with congenital heart disease (CHD) and low birth weight. METHODS: One hundred and ninety-four CHD children, aged 6 months to 2 years, weighting 5 to 10 kg, were selected for this study. The 94 boys and 100 girls with the American Society of Anesthesiologists (ASA) physical status III and IV were randomly divided into two groups each consisting of 97 patients, and were subjected to ultra-fast-track and conventional anesthesia for cardiac surgery. For children in UFTA group, sevoflurane was stopped when cardiopulmonary bypass (CPB) started and cis-atracurium was stopped at the beginning of rewarming, and remifentanil (0.3 µg/kg/mim) was then infused. Propofol and remifentanil were discontinued at skin closure. 10 min after surgery, extubation was performed in operating room. For children in conventional anesthesia group, anesthesia was given routinely and they were directly sent to ICU with a tracheal tube. Extubation time, ICU stay and hospital stay after operation were recorded. Sedation-agitation scores (SAS) were assessed and adverse reactions as well as other anesthesia -related events were recorded. RESULTS: The extubation time, ICU stay and hospital stay were significantly shorter in UFTA group (P < 0.05) and SAS at extubation was lower in UFTA group than in conventional anesthesia group, but similar in other time points. For both groups, no airway obstruction and other serious complications occurred, and incidence of other anesthesia -related events were low. CONCLUSIONS: UFTA shortens extubation time, ICU stay and hospital stay for children with CHD and does not increase SAS and incidence of adverse reactions.

Catalyst- and Additive-Free Cascade Reaction of Isoquinoline N-Oxides with Alkynones: An Approach to Benzoazepino[2,1-a]isoquinoline Derivatives.

A cascade reaction of isoquinoline N-oxides with alkynones was developed, delivering a fluorescent benzoazepino[2,1-a]isoquinoline derivative. The reaction worked smoothly without requirement of any catalyst or additive, making this method economical and easy to handle.

MiR-205 suppresses epithelial-mesenchymal transition and inhibits tumor growth of human glioma through down-regulation of HOXD9.

Epithelial-mesenchymal transition (EMT) plays a pivotal role in cancer progression. Hsa-miR-205 is considered one of the fundamental regulators of EMT. In the present study, we found that miR-205 was down-regulated in glioma tissues and human glioma cells U87 and U251. Meanwhile, miR-205 overexpression enhanced E-cadherin, reduced mesenchymal markers, and decreased cell proliferation, migration, and invasion in vitro. In vivo, miR-205 suppressed tumor growth. Additionally, HOXD9 was confirmed as a direct target of miR-205. Suppression of HOXD9 by miR-205 was demonstrated by luciferase reporter assay, quantitative real time-PCR analysis, and western blot. Moreover, we observed a negative correlation between miR-205 and HOXD9 in human glioma tissues. In summary, our findings demonstrated that miR-205 suppresses glioma tumor growth, invasion, and reverses EMT through down-regulating its target HOXD9.

Implementation of National Health Informatization in China: Survey About the Status Quo.

BACKGROUND: The National Health and Family Planning Commission (NHFPC) in China organized a nationwide survey to investigate the informatization in hospitals and regional Health and Family Planning Commissions (HFPCs) in 2017. The survey obtained valid results from 79.69% (2021/2536) of major hospitals and 81% (26/32) of provincial and 73.1% (307/420) of municipal HFPCs. The investigated topics covered hardware infrastructure, information resources, applications, systems, and organizations in health informatics. OBJECTIVE: This study aimed to provide evidence collected from the survey regarding China's health informatization and assist policy making regarding health informatics in the 13th Five-Year Plan of China. METHODS: Based on the survey, the paper presented the status quo of China's health informatization and analyzed the progress and potential problems in terms of the country's health information development policies. RESULTS: Related policies have helped to construct 4-level information platforms and start converging the regional data to the 3 centralized databases. The principle of informatics has been transiting from finance-centered to people-centered. Alternatively, the quality, usability, and interoperability of the data still need to be improved. CONCLUSIONS: The nationwide survey shows that China's health informatization is rapidly developing. Current information platforms and databases technically support data exchanging between all provinces and cities. As China is continuing to improve the infrastructure, more advanced applications are being developed upon it.

Rhynchophylline attenuates allergic bronchial asthma by inhibiting transforming growth factor-ß1-mediated Smad and mitogen-activated protein kinase signaling transductions in vivo and in vitro.

Rhynchophylline (Rhy) is a major active component of Uncaria rhynchophylla and exhibits the potential to inhibit the proliferation of airway smooth muscle cells (ASMCs). In the current study, it was hypothesized that Rhy serves a key role in the anti-asthma effect of Uncaria rhynchophylla by inhibiting transforming growth factor-ß1 (TGF-ß1)-mediated activation of Smad and mitogen-activated protein kinase (MAPK) signaling. Allergic asthma was induced in mice using ovalbumin (OVA), and the effect of Rhy treatment on inflammatory and allergic responses in the bronchoalveolar lavage fluid (BALF) and serum of mice was determined. Subsequently, the changes in TGF-ß1-induced Smad and MAPK signaling following Rhy administration were detected to determine the mechanism associated with this treatment. In addition, TGF-ß1 was employed to induce hyperplasia of ASMCs, and the effect of Rhy on proliferation of ASMCs, and Smad and MAPK signaling in vitro was also assessed. The administration of Rhy attenuated the recruitment of eosinophils in BALF induced by OVA, which was associated with the suppressed production of immunoglobulin E, interleukin (IL)-13, IL-4 and IL-5. At the molecular level, the administration of Rhy suppressed the expression levels of TGF-ß1, Smad4, p-Smad2 and p-Smad3, while it induced the expression of Smad7, indicating the inhibitory effect of Rhy on TGF-ß1-mediated Smad and MAPK signaling. Furthermore, Rhy inhibited the proliferation of ASMCs and, similar to the results of the in vivo assay, it blocked the pro-hyperplasia signaling transduction in vitro. In conclusion, the current study demonstrated the anti-asthma effect of Rhy, which depended on the inhibition of TGF-ß1-mediated Smad and MAPK signaling.

Long noncoding RNA DANCR mediates cisplatin resistance in glioma cells via activating AXL/PI3K/Akt/NF-κB signaling pathway.

Malignant glioma is an aggressive type of brain tumor with poor prognosis and mostly incurable. Although cisplatin is used for adjuvant chemotherapy against glioma, intrinsic and acquired resistance restricts the application of cisplatin. Long noncoding RNA (lncRNA) DANCR is reported to regulate the differentiation and progression of several cancers. However, whether DANCR participates in cisplatin resistance of glioma is still unknown. In this study, we found that DANCR expression was negatively correlated with cisplatin sensitivity in glioma cells. Gain-of and loss-of function assays revealed that DNACR attenuated cisplatin-induced cell proliferation inhibition in vitro and xenograft growth suppression in vivo. Furthermore, DNACR also attenuated cisplatin-induced cell apoptosis in vitro and in vivo. Mechanistically, we found that DANCR upregulated AXL via competitively binding miR-33a-5p, miR-33b-5p, miR-1-3p, miR-206, and miR-613. Through upregulating AXL, DANCR activated PI3K/Akt/NF-κB signaling pathway in glioma cells. Inhibiting AXL/PI3K/Akt/NF-κB signaling pathway reversed the effects of DANCR on cisplatin resistance. In conclusion, we identified a cisplatin-resistance associated lncRNA DANCR. DANCR promotes cisplatin resistance via activating AXL/PI3K/Akt/NF-κB signaling pathway in glioma. Our data suggested that DANCR would be a potential biomarker for predicting cisplatin sensitivity and a therapeutic target for enhancing cisplatin efficacy in glioma.

The application of improved abdominal wall punctures technique in ventriculoperitoneal shunt for hydrocephalus: a retrospective analysis versus open mini-laparotomy.

PURPOSE: Ventriculoperitoneal shunt (VPS) remains as one of the main treatment for hydrocephalus. The traditional technique for placing the distal ends of shunts is via a mini-laparotomy. However, laparotomies are relatively time consuming. Trocars to penetrate abdominal wall by blind puncture have been used. Here, we report on the abdominal wall puncture technique, and compare the possible complications and outcomes with traditional mini-laparotomy. MATERIALS AND METHODS: We use a 5mm incision at the inverse McBurney point. The abdominal wall on both sides of the incision point is lifted with two towel clips prior to puncture to create a potential gap between the abdominal wall and viscera. After the puncture, a guide wire is inserted followed by a dilator, introducer and the distal shunt tubing using a Seldinger technique. In this process, the operator feels resistance give with breakthrough of parietal peritoneal. After the insertion of introducer, a negative pressure injection test helps confirm whether the introducer is inside the peritoneum. RESULTS: Operative time is less than with mini-laparotomies. Postoperative abdominal symptoms are mild. Out of 29 patients there were no puncture related complications. CONCLUSION: The improved abdominal-wall puncture technique is a simple, fast, economical and effective method. Patients, who are treated by the method, generally experience rapid postoperative recoveries.

XRCC1 genetic polymorphism acts a potential biomarker for lung cancer.

Lung cancer is one of the most common but serious cancers in the world. Both the X-ray repair cross-complementing group 1 (XRCC1) gene and the human multidrug resistance 1 (MDR1) gene are important candidate genes influencing the susceptibility to various diseases, including lung cancer. This study aimed to assess the correlation of genetic polymorphisms in XRCC1 and MDR1 with the susceptibility to lung cancer. In this study, a total of 320 lung cancer patients and 346 cancer-free controls in Chinese population were enrolled in this study. Data about the clinical characteristics and related risk factors of lung cancer were collected by questionnaires. The single-nucleotide polymorphisms (SNPs) of XRCC1 and MDR1 genes were genotyped by created restriction site-polymerase chain reaction method. Our data showed that the risk for lung cancer increased significantly among the variant Arg194Trp (C > T, rs1799782) and Arg399Gln (G > A, rs25487) of XRCC1, but there are no significant differences in the allelic and genotypic frequencies of c.1564A > T and c.3073A > C of MDR1 between lung cancer patients and cancer-free controls. In conclusion, these preliminary results suggest that the C > T, rs1799782 and C > T, rs25487 of XRCC1 genetic variants might be used as molecular markers for detecting lung cancer susceptibility.

Association between the lipoprotein-associated phospholipase A2 activity and the progression of subclinical atherosclerosis.

AIM: The lipoprotein-associated phospholipase A2(Lp-PLA2) level has been shown to be associated with the risk of clinical cardiovascular events. We aimed to investigate whether Lp-PLA2 is associated with the progression of subclinical atherosclerosis in the general population. METHODS: The degree of carotid plaque and the maximal intima-media thickness(IMT) were measured twice over a 5-year interval in 913 participants 45 to 74 years of age at baseline in a cohort study. The associations between the plasma Lp-PLA2 activity and the progression of carotid plaque and changes in the IMT level were assessed according to sex after adjusting for traditional risk factors and the high-sensitivity C-reactive protein(hsCRP) level. RESULTS: During the 5-year follow-up period, the progression of plaque was observed in 58.5% of men and 48.3% of women. The median maximal IMT level increased by 0.12 mm in men and 0.09 mm in women per year. The progression of plaque and changes in the IMT level increased according to the quartile of the Lp-PLA2 activity in men(p＜0.05 for trend), but not women. Following adjustment for traditional risk factors and the hsCRP level, the odds ratio for plaque progression associated with an increase in the Lp-PLA2 activity of one standard deviation was 1.28(95% CI=1.09-1.49, p=0.043) in men and 0.92(95% CI=0.78-1.08, p=0.273) in women. The regression coefficient for IMT progression was 0.003(p=0.004) in men and -0.001(p=0.166) in women after adjusting for the other factors. CONCLUSIONS: The Lp-PLA2 level is associated with the progression of subclinical atherosclerosis in men. Lp-PLA2 may play an important role in the pathogenesis of atherosclerosis and be a potential target for the early prevention of cardiovascular disease.

Large-scale prediction of human kinase-inhibitor interactions using protein sequences and molecular topological structures.

The kinase family is one of the largest target families in the human genome. The family's key function in signal transduction for all organisms makes it a very attractive target class for the therapeutic interventions in many diseases states such as cancer, diabetes, inflammation and arthritis. A first step toward accelerating kinase drug discovery process is to fast identify whether a chemical and a kinase interact or not. Experimentally, these interactions can be identified by in vitro binding assay - an expensive and laborious procedure that is not applicable on a large scale. Therefore, there is an urgent need to develop statistically efficient approaches for identifying kinase-inhibitor interactions. For the first time, the quantitative binding affinities of kinase-inhibitor pairs are differentiated as a measurement to define if an inhibitor interacts with a kinase, and then a chemogenomics framework using an unbiased set of general integrated features (drug descriptors and protein descriptors) and random forest (RF) is employed to construct a predictive model which can accurately classify kinase-inhibitor pairs. Our results show that RF with integrated features gave prediction accuracy of 93.76%, sensitivity of 92.26%, and specificity of 95.27%, respectively. The results are superior to those by only considering two separated spaces (chemical space and protein space), demonstrating that these integrated features contribute cooperatively. Based on the constructed model, we provided a high confidence list of drug-target associations for subsequent experimental investigation guidance at a low false discovery rate.

Genome-scale screening of drug-target associations relevant to Ki using a chemogenomics approach.

The identification of interactions between drugs and target proteins plays a key role in genomic drug discovery. In the present study, the quantitative binding affinities of drug-target pairs are differentiated as a measurement to define whether a drug interacts with a protein or not, and then a chemogenomics framework using an unbiased set of general integrated features and random forest (RF) is employed to construct a predictive model which can accurately classify drug-target pairs. The predictability of the model is further investigated and validated by several independent validation sets. The built model is used to predict drug-target associations, some of which were confirmed by comparing experimental data from public biological resources. A drug-target interaction network with high confidence drug-target pairs was also reconstructed. This network provides further insight for the action of drugs and targets. Finally, a web-based server called PreDPI-Ki was developed to predict drug-target interactions for drug discovery. In addition to providing a high-confidence list of drug-target associations for subsequent experimental investigation guidance, these results also contribute to the understanding of drug-target interactions. We can also see that quantitative information of drug-target associations could greatly promote the development of more accurate models. The PreDPI-Ki server is freely available via: http://sdd.whu.edu.cn/dpiki.

Gold(I)-catalyzed regiodivergent rearrangements: 1,2- and 1,2'-alkyl migration in skipped alkynyl ketones.

A series of 2-alkynyl carbonyl compounds that contain a cyclopentene ring or a heterocycle can be transformed into various fused dihydrobenzofurans and tetrahydrofuro[2,3-c]pyridines by means of a 1,2-alkyl migration process. Both of these reactions proceed with excellent regioselectivity and stereospecificity when using a cationic gold(I) catalyst. Treatment of 4-styrylcyclopent-1-enecarboxylates under different conditions affords a range of highly functionalized dihydrobenzofurans and dihydroisobenzofurans. A divergence in product selectivity, which depends on the anion of the silver salts used, was observed. Interestingly, ring-fused tetrahydroquinolines undergo only 1,2'-alkyl migration reaction by means of a C-C cleavage/cyclization sequence to provide tetrahydroazepine derivatives. Mechanistic studies suggest that the gold complexes catalyze 1,2-alkyl migration reactions through a concerted reaction pathway and 1,2'-alkyl migration reactions through a stepwise reaction pathway.

Local delivery of slow-releasing temozolomide microspheres inhibits intracranial xenograft glioma growth.

BACKGROUND: Currently, treatment of malignant gliomas with temozolomide in addition to surgical resection and radiotherapy remains the foundation of glioma therapy. In an effort to develop new therapeutic choices to treat malignant gliomas, we have designed slow-releasing microspheres that deliver temozolomide (P-TMZ). The local continuous release of temozolomide at the intracranial tumor site may overcome many obstacles associated with systemic delivery, which will help to further improving the therapeutic effects against malignant gliomas. METHODS: Slow-releasing microspheres containing 10 % temozolomide were prepared, the antitumor efficacy in vitro was evaluated with MTT assay, and the therapeutic efficacy in vivo against gliomas was assessed in human glioma (SGH44) nude mice s.c. and orthotopic xenograft models. RESULTS: A single local injection of P-TMZ led to significant reduction both in s.c. and orthotopic human SHG44 glioma xenografts. P-TMZ, BCNU and TMZ had significant antiglioma effect (P < 0.01), their IC50 value was all less than 10 µg/ml. Tumor inhibition ratio of P-TMZ, BCNU and TMZ in vivo was higher than empty microspheres P0 (P < 0.01); P-TMZ and BCNU showed higher antitumor efficacy than TMZ (P < 0.05). CONCLUSIONS: Our present results suggest that local delivery of slow-releasing temozolomide microspheres is effective for malignant gliomas. P-TMZ retained good antitumor activity and had better therapeutic effect against glioma both in vitro and in vivo, which provide a new choice for future clinical interstitial chemotherapy.

DBU-catalyzed tandem additions of electron-deficient 1,3-conjugated enynes with 2-aminomalonates: a facile access to highly substituted 2-pyrrolines.

An efficient, metal free approach to highly substituted 2-pyrrolines by DBU-catalyzed tandem additions (a formal [3+2] cycloaddition) of electron-deficient 1,3-conjugated enynes and 2-aminomalonates under mild conditions was developed.

Association of self-reported snoring with carotid artery intima-media thickness and plaque.

Previous studies have suggested that self-reported snoring is associated with atherosclerotic vascular diseases. However, the role of self-reported snoring as an independent risk factor for subclinical atherosclerosis has not been well established. This study aimed to evaluate whether and to what extent self-reported snoring is associated with subclinical carotid atherosclerosis after adjusting for traditional cardiovascular risk factors. Carotid intima-media thickness and plaque were investigated with ultrasonography in 1245 urban Chinese aged 50-79 years between September 2007 and November 2007. Information on self-reported snoring and measurements of traditional cardiovascular risk factors was also collected. A total of 1050 participants were involved in the final analysis. The prevalence of self-reported snoring habitually (snoring frequency ≥5 days per week) was 31.5, and 64.3% of the participants in this population had a history of snoring. The mean values of the maximum intima-media thickness of bifurcation and common carotid arteries in snorers were significantly higher than in non-snorers (1.08 ± 0.14 mm versus 1.04 ± 0.14 mm, P < 0.001, in carotid bifurcation; 1.03 ± 0.15 mm versus 1.00 ± 0.15 mm, P = 0.002, in common carotid artery). After adjustment for traditional cardiovascular risk factors, logistic regression analysis showed that the odds ratio of self-reported snoring habitually for increased intima-media thickness and carotid bifurcation plaque was 1.71 [95% confidence interval (CI): 1.22-2.39; P = 0.002] and 3.63 (95% CI: 2.57-5.12; P < 0.001), respectively. In conclusion, the current study suggested that self-reported snoring is associated significantly with carotid bifurcation intima-media thickness and the presence of plaque, independent of traditional cardiovascular risk factors.