A promising strategy to improve the stability and immunogenicity of killed but metabolically active vaccines: low-temperature preparation and coating of nanoparticles.

Bacteria are becoming an increasingly serious threat to human health. The emergence of super bacteria makes clinical treatment more difficult. Vaccines are one of the most effective means of preventing and treating bacterial infections. As a new class of vaccines, killed but metabolically active (KBMA) vaccines provide the immunogenicity of live vaccines and the safety of inactivated vaccines. Herein, a promising strategy is proposed to improve the stability and immunogenicity of KBMA vaccines. KBMA vaccines were produced at low temperature (4 °C), and the bacterial surface was engineered using mesoporous silica nanoparticle (MSN) coating. Compared to vaccines prepared at room temperature, the metabolic activity of KBMA vaccines prepared at 4 °C remarkably improved. Benefiting from the induction of MSNs, the stability of KBMA vaccines was increased and the preservation time was prolonged at 4 °C. Meanwhile, metabolomics analysis showed that the metabolite spectrum of live bacteria changed after photochemical treatment and MSN coating, which interfered with organic acid metabolism pathways, lipid metabolism and biosynthesis of secondary metabolites. Furthermore, the immune response in the mice treated with KBMA/MSN vaccines was similar to that in those treated with live vaccines and stronger than that in those treated with inactivated vaccines. In comparison with the control group, bacteria tissue burdens of KBMA/MSN group were significantly reduced. CD4+ T cells dominated immune responses for the protection of mice. Thus, the current work promotes the application of KBMA vaccines, providing an alternative choice for treating bacterial infections.

Structurally diverse diterpenoids from the seeds of Caesalpinia minax Hance and their bioactivities.

Eight previously undescribed diterpenoids, caesamins A-H (1-8), were separated and identified from the seeds of Caesalpinia minax Hance. Their structures were characterized by extensive spectroscopic data and X-ray crystallographic analysis. Structurally, caesamin A (1) is the first cassane-type diterpenoid with a C23 carbon skeleton containing an unusual isopropyl. Caesamin F (6) represents the first example of cleistanthane diterpenoid from the genus Caesalpinia. Caesamins B (2) and F (6) exhibited inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 45.67 ± 0.92 and 42.99 ± 0.24 µM, comparable to positive control 43.69 ± 2.62 µM of NG-Monomethyl-L-arginine. Furthermore, the chemotaxonomic significance of the isolates was discussed.

Anti-pancreatic cancer activity of cassane diterpenoids isolated from the seeds of Caesalpinia sappan mediated by autophagy activation via ROS/AMPK/mTORC1 pathway.

Three undescribed cassane diterpenoids, caesalpanins D-F (1-3), and seven known ones were isolated from the seeds of Caesalpinia sappan. Structures and absolute configurations of 1-3 were elucidated based on the extensive spectroscopic analysis, single-crystal X-ray diffraction analysis, and ECD calculations. Structurally, compound 1 was the first example of 18-norcassane diterpenoid and 2 was a rare 20-norcassane diterpenoid having an unusual five-membered oxygen bridge between C-10/C-18. The anti-proliferative activity of 1, 3, and 4-10 against PANC-1 cells (pancreatic ductal adenocarcinoma cell line) was evaluated, and phanginin H (4) was found to exhibit anti-cancer activity with IC50 value of 18.13 ± 0.63 µM. Compound 4 inhibited PANC-1 cell growth by arresting the cell cycle at G2/M phase via regulation of cyclin-dependent kinases, and the self-renewal and metastasis of PANC-1 cells by suppressing cancer cell stemness. Furthermore, compound 4 induced ROS generation and subsequently activated autophagy, which was demonstrated by the formation of autophagic vacuoles and dynamic change of autophagic flux. The induced ROS accumulation resulted in AMPK activation and subsequently regulation of mTORC1 activity and ULK phosphorylation, indicating that 4 triggered autophagy through ROS/AMPK/mTORC1 pathway. These findings suggested that 4 might potentially be an autophagy inducer for the therapy of pancreatic cancer.

Multisystem inflammatory syndrome in children in the context of coronavirus disease 2019 pandemic / 中国当代儿科杂志

Multisystem inflammatory syndrome in children (MIS-C) is a complex syndrome characterized by multi-organ involvement that has emerged in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak. The clinical presentation of MIS-C is similar to Kawasaki disease but predominantly presents with fever and gastrointestinal symptoms, and severe cases can involve toxic shock and cardiac dysfunction. Epidemiological findings indicate that the majority of MIS-C patients test positive for SARS-CoV-2 antibodies. The pathogenesis and pathophysiology of MIS-C remain unclear, though immune dysregulation following SARS-CoV-2 infection is considered a major contributing factor. Current treatment approaches for MIS-C primarily involve intravenous immunoglobulin therapy and symptomatic supportive care. This review article provides a comprehensive overview of the definition, epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of MIS-C.

Diagnosis and treatment of incomplete Kawasaki disease in children / 中国当代儿科杂志

Kawasaki disease (KD) is a febrile disease mainly observed in children aged <5 years, with medium- and small-vessel vasculitis as the main lesion. Although KD has been reported for more than 50 years and great progress has been made in the etiology and pathology of KD in recent years, there is still a lack of specific indicators for the early diagnosis of KD, especially with more difficulties in the diagnosis of incomplete Kawasaki disease (IKD). At present, there are no clear diagnostic criteria for IKD, which leads to the failure of the timely identification and standardized treatment of IKD in clinical practice and even induce the development of coronary artery lesion. This article reviews the concept, epidemiological features, diagnosis, treatment, and follow-up management of IKD, in order to deepen the understanding of IKD among clinical workers and help to improve the clinical diagnosis and treatment of KD in China.

Transurethral columnar balloon dilation of the prostate for small volume prostatic hyperplasia:a single-center,open,randomized controlled clinical trial / 现代泌尿外科杂志

【Objective】 To compare the efficacy of transurethral columnar balloon dilation of the prostate (TUCBDP) and transurethral resection of prostate (TURP) in the treatment of small volume prostatic hyperplasia. 【Methods】 A total of 96 patients with small volume prostatic hyperplasia diagnosed in our hospital during Jan.2019 and Jan.2021 were enrolled and divided into the observation group and control group,with 48 patients in either group. The observation group received TUCBDP while the control group TURP. The International Prostate Symptom score (IPSS),Quality of Life Score (QOL), international index of erectile function-erectile function (IIEF-EF),maximum urinary flow rate (Qmax),postvoid residual urine (PVR) and maximum detrusor pressure (MDP) of the two groups were compared before surgery and 24 months after surgery. The surgery-related complications and occurrence of new or aggravated sexual dysfunction were observed. 【Results】 Both groups successfully completed the treatment. The operation time and indwelling catheterization time were shorter in the observation group than in the control group (P<0.05). The scores of QOL,IPSS and IIEF-EF,the levels of Qmax,PVR and MDP of both groups 24 months after surgery were significantly improved compared with those before surgery (P<0.05). The IPSS score of the observation group was lower than that of the control group 24 months after surgery (P<0.05),while the IIEF-EF score and Qmax of the observation group were higher than those of the control group (P<0.05). The incidences of surgery-related complications and new or aggravated sexual dysfunction were significantly lower in the observation group than in the control group (P<0.05). 【Conclusion】 TUCBDP is significantly effective in the treatment of small volume prostatic hyperplasia,showing greater advantages than TURP in improving postoperative IPSS,IIEF-EF score and Qmax,with higher safety.

Clinical efficacy of in vitro local high-frequency hyperthermia combined with drugs in the treatment of type Ⅲb chronic prostatitis / 现代泌尿外科杂志

【Objective】 To investigate the efficacy of in vitro local high-frequency hyperthermia combined with drugs in the treatment of type Ⅲb chronic prostatitis (CP). 【Methods】 A total of 148 patients with type Ⅲb CP treated in our hospital during Jun.2020 and Jun.2022 were randomly divided into control group (n=74) and combination group (n=74). The control group received only drug treatment, while the combination group received extracorporeal local high-frequency hyperthermia treatment. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), maximum urinary flow rate (MFR), average urinary flow rate (AFR) and International Index of Erectile Function-5 (IIEF-5) score were compared between the two groups. 【Results】 There were no significant differences between the two groups in terms of NIH-CPSI, MFR, AFR and IIEF-5 score before treatment(P>0.05). After treatment, these indexes increased in both groups (P<0.05), and the improvements in the combination group were more significant (P<0.05). 【Conclusion】 Medication combined with in vitro local high-frequency hyperthermia is effective in improving the clinical symptoms of type Ⅲb CP, which is worth clinical promotion.

Research advances in genetic polymorphisms in Kawasaki disease / 中国当代儿科杂志

Kawasaki disease (KD) is a systemic inflammatory vascular disorder that predominantly affects children and is the leading cause of acquired heart disease in children. Although the etiology of this disease remains unclear, genome-wide association and genome-wide linkage studies have shown that some susceptible genes and chromosomal regions are associated with the development and progression of KD. With the advancement of high-throughput DNA sequencing techniques, more and more genomic information related to KD is being discovered. Understanding the genes involved in the pathogenesis of KD may provide novel insights into the diagnosis and treatment of KD. By analyzing related articles and summarizing related research advances, this article mainly discusses the T cell activation-enhancing genes that have been confirmed to be closely associated with the development and progression of KD and reveals their association with the pathogenesis of KD and coronary artery lesions.

Strengthening the prevention and treatment of Omicron infection in children / 中国当代儿科杂志

Omicron is a newly discovered variant virus of coronavirus disease 2019 and has spread rapidly around the world. Omicron has been defined as a variant of concern by the World Health Organization. Its epidemiology, pathogenic characteristics, clinical diagnosis, treatment, and prevention are still being observed and summarized, and in particular, there are few reports on the diagnosis and treatment of children with Omicron infection. This article introduces the influence of Omicron infection in children and its prevention, diagnosis, and treatment.

Interpretation of the JCS/JSCS 2020 guideline on diagnosis and management of cardiovascular sequelae in Kawasaki disease / 中国当代儿科杂志

Kawasaki disease is the main cause of acquired heart disease in children. The cardiovascular sequelae of Kawasaki disease, such as coronary artery lesion and giant coronary aneurysm, have a great impact on children's physical and mental health. The Japanese Circulatory Society and the Japanese Society of Cardiac Surgery jointly released the JCS/JSCS 2020 guideline on diagnosis and management of cardiovascular sequelae in Kawasaki disease in July, 2020, which systematically introduces the advances in the diagnosis and management of cardiovascular sequelae of Kawasaki disease. The article gives an interpretation in the severity evaluation of Kawasaki disease and diagnosis, treatment and long-term management of cardiovascular sequelae in the guideline.

Seminal plasma miR-210-3p induces spermatogenic cell apoptosis by activating caspase-3 in patients with varicocele.

The aim of this study was to investigate the role of seminal plasma miR-210-3p in the impairment of semen quality caused by varicocele. This study included 102 patients whose semen quality was normal when they were diagnosed with varicocele. A 2-year follow-up for included patients was performed, and they were divided into Group A (semen quality became abnormal) and Group B (semen quality remained normal) according to the results of semen analysis during the follow-up. Semen parameters and seminal plasma miR-210-3p expression were investigated by semen analysis and quantitative real-time polymerase chain reaction, respectively. In vitro experiments with GC-2 cells were performed to explore the role of miR-210-3p in spermatogenic cells. The results of quantitative real-time polymerase chain reaction showed that the level of seminal plasma miR-210-3p in Group A was higher than that in Group B both after 2-year follow-up and when they were diagnosed with varicocele (both P < 0.01). Apoptosis and proliferation assays showed that miR-210-3p induces apoptosis of spermatogenic cells by promoting caspase-3 activation. In conclusion, our study indicated that seminal plasma miR-210-3p induces spermatogenic cell apoptosis by activating caspase-3 in patients with varicocele. Seminal plasma miR-210-3p may be a potential biomarker for predicting impaired semen quality caused by varicocele.

Kawasaki disease - a new manifestation of COVID-19 in children / 中国当代儿科杂志

Since the outbreak of coronavirus disease 2019 (COVID-19) in Europe and America, the incidence of Kawasaki disease has significantly increased, which has aroused concern among pediatricians and parents. COVID-19 can cause inflammation reactions of multiple organs, which is similar to the systemic vasculitis of Kawasaki disease, and even COVID-19 can cause skin rash on the extremities of the limbs, which is also similar to Kawasaki disease. The cause of Kawasaki disease is currently unclear, and it cannot be ruled out that COVID-19 is associated with an increased incidence of Kawasaki disease. Therefore, during the epidemic of COVID-19, if children have symptoms similar to Kawasaki disease, intravenous immunoglobulin is recommended as early as possible to reduce the incidence of coronary artery lesions.

A review on the role of angiotensin-converting enzyme 2 in children with coronavirus disease 2019 / 中国当代儿科杂志

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) all over the world, there is an increasing number of children with such infection. Angiotensin-converting enzyme 2 (ACE2), one of the binding sites for SARS-CoV-2 infection in humans, can bind to viral spike proteins, allowing transmembrane serine protease (TMPRSS2) to activate S-protein to trigger infection and induce the production of various inflammatory factors such as interleukin-1, interferon-l, and tumor necrosis factor. Compared with adults, children tend to have lower expression levels of ACE2 and TMPRSS2, which are presumed to be associated with milder symptoms and fewer cases in children. The article summarizes the research advances in the role of ACE2 during SARS-CoV-2 infection, in order to help understand the pathogenic mechanism of SARS-CoV-2 and provide a reference for better development of drugs and vaccines to prevent and treat coronavirus disease 2019 in children.

Rapid magnetic solid-phase extraction based on alendronate sodium grafted mesoporous magnetic nanoparticle for the determination of trans-resveratrol in peanut oils.

In the present study, a rapid and effective method based on alendronate sodium grafted mesoporous magnetic nanoparticle (Fe3O4@ANDS) extraction for the determination of trans-resveratrol (TRA) in peanut oils was developed by coupling with HPLC-UV detection. The Fe3O4@ANDS was prepared via Lewis acid/base interaction which was simply carried out in mild aqueous condition without the using of organic solvent. The resultant Fe3O4@ANDS encompassed amino group on its surface, and it was employed as magnetic solid-phase extraction adsorbent for purification and enrichment of TRA from peanut oils through hydrogen bond interaction. Under the optimized conditions, the whole pretreatment process could be accomplished within 10 min without time-consuming concentrated and reconstituted process. The linearity range of the proposed method was 1-10,000 ng/g with satisfactory correlation coefficient (R2) of 0.9992. The recoveries in spiked oil samples were in the range of 78.6-118.9% with the RSDs less than 3.3% (intra-day) and 15.2% (inter-day). The limit of detection for TRA in peanut oils was 0.3 ng/g which was comparative to the reported methods by using LC-MS/MS detection. Finally, the established method was successfully applied to the analysis of TRA in several peanut oils with different brands from local market as well as other kinds of vegetable oils.

A minimally invasive alternative for the treatment of nutcracker syndrome using individualized three-dimensional printed extravascular titanium stents / 中华医学杂志(英文版)

BACKGROUND@#This study was designed to evaluate the clinical and radiographic outcomes of patients with nutcracker syndrome (NCS) who were treated with three-dimensional printing (3DP) extravascular titanium stents (EVTSs). The 3DP EVTS was expected to release the hypertension of the left renal vein (LRV) produced by its compression between the superior mesenteric artery (SMA) and the aorta without causing any complications.@*METHOD@#The pre-operative kidney model of each patient was printed out to enable surgical planning. After that, the EVTS was designed based on the LRV's primitive physiologic structure using computer-aided design software, and each stent was printed out with a precision setting of 20 μm. Seventeen patients who had been suffering from NCS underwent laparoscopic 3DP EVTS placement. The surgical procedure was designed for the placement of EVTS, taking great care in positioning and fixing the stent. Surgical data, which included patient demographic characteristics as well as pre- and post-operative test results, were collected and analyzed.@*RESULTS@#The mean duration of surgery was 75 ± 9 min, and the mean blood loss was 20 ± 5 mL. Computed tomography examinations revealed that the pre- and post-operative angle between the SMA and the aorta ranged from 18.7° ± 4.3° to 48.0° ± 8.8° (P < 0.05); in patients with left varicocele, the mean diameter of the left spermatic vein ranged from 3.7 ± 0.5 to 1.3 ± 0.2 mm (P < 0.05). Moreover, Doppler ultrasound examinations showed that the peak velocity of blood flow at the hilar area ranged from 12.4 ± 3.3 to 18.5 ± 3.4 cm/s (P < 0.05). No side effects were observed in the 24 to 42 months following surgery.@*CONCLUSION@#The findings after 2 years of follow-up suggest that the 3DP EVTS is a safe and effective minimally invasive alternative for the treatment of NCS.

A minimally invasive alternative for the treatment of nutcracker syndrome using individualized three-dimensional printed extravascular titanium stents / 中华医学杂志(英文版)

Background@#This study was designed to evaluate the clinical and radiographic outcomes of patients with nutcracker syndrome (NCS) who were treated with three-dimensional printing (3DP) extravascular titanium stents (EVTSs). The 3DP EVTS was expected to release the hypertension of the left renal vein (LRV) produced by its compression between the superior mesenteric artery (SMA) and the aorta without causing any complications.@*Method@#The pre-operative kidney model of each patient was printed out to enable surgical planning. After that, the EVTS was designed based on the LRV’s primitive physiologic structure using computer-aided design software, and each stent was printed out with a precision setting of 20 μm. Seventeen patients who had been suffering from NCS underwent laparoscopic 3DP EVTS placement. The surgical procedure was designed for the placement of EVTS, taking great care in positioning and fixing the stent. Surgical data, which included patient demographic characteristics as well as pre- and post-operative test results, were collected and analyzed.@*Results@#The mean duration of surgery was 75 ± 9 min, and the mean blood loss was 20 ± 5 mL. Computed tomography examinations revealed that the pre- and post-operative angle between the SMA and the aorta ranged from 18.7° ± 4.3° to 48.0° ± 8.8° (P < 0.05); in patients with left varicocele, the mean diameter of the left spermatic vein ranged from 3.7 ± 0.5 to 1.3 ± 0.2 mm (P < 0.05). Moreover, Doppler ultrasound examinations showed that the peak velocity of blood flow at the hilar area ranged from 12.4 ± 3.3 to 18.5 ± 3.4 cm/s (P < 0.05). No side effects were observed in the 24 to 42 months following surgery.@*Conclusion@#The findings after 2 years of follow-up suggest that the 3DP EVTS is a safe and effective minimally invasive alternative for the treatment of NCS.

Research progress on rheology in the holt melt extrusion / 中国药学杂志

Hot melt extrusion (HME) is a novel technique to prepare solid dispersions and granules. During the manufacturing process, the drugs and polymers melt and show the complex rheological properties under the heat and forces of shear and extension. Rheology is a potential tool to guide their formulations, manufacturing process and in-line quality control. In this review, we summarized the basic theories of the molten polymer viscoelasticity with temperature and shear rate, and the time-temperature superposition, the widely used rheometries and their applications in the pharmaceutical polymer thermoplasticity, drug solubility and interactions in the molten polymers, manufacturing parameters and the in-line quality control of hot melt extrusion.

Design, synthesis, and biological evaluation of new B-RafV600E kinase inhibitors.

The association of deregulated signal pathways with various diseases has long been a research hotspot. One of the most important signal pathways, the MAPK (mitogen-activated protein kinase) signal pathway, plays a vital role in transducing extracellular signals into vital intracellular mechanisms. While mutations on its key component Raf kinase lead to sever diseases, targeted inhibition has thereby become an attractive therapeutic strategy. Several drugs have been approved for the treatment of Raf relevant diseases, yet more candidates are ever needed as the known drugs have confronted resistance and side effects. In the present study, we primarily investigated the binding modes of type I/II and type II inhibitors with B-Raf kinase. Based on the current knowledge, these ligands were fragmented and recombined to provide new interesting insights. Afterwards, a series of derivatives has been synthesized after the validation of hit compound. In addition, in vitro assays were carried out to profile the pharmacological properties of all the entities. Of all the compounds, compound 5h showed the best profile and may be used in the future study.

Assessment of Height Prediction Model Based on SNPs Loci / 法医学杂志

Objective To establish a height prediction model of Chinese Han male based on the reported 547 height-associated single nucleotide polymorphisms (SNPs) loci in Europeans, and assess its accuracy for height estimation. Methods The DNA typing was analyzed in 59 Han male samples of Shandong province by Affymetrix SNP Array 6.0 chip and HiSeq 4000 sequencing platform. Prediction model was established using 547 height-associated SNPs loci as predictors and weight allele sums (WAS) as com-puting method. The accuracy of height prediction model was analysed using receiver operating characteris-tic (ROC) curve and area under curve (AUC). Results There was no height-associated SNPs locus was found by genome-wide association studies. In present study, height prediction model was established by WAS and obtained an AUC of 0.67 (95％CI:0.53-0.90). Conclusion It has reference value for predicting the height of Han male in Shandong province by WAS model based on 547 SNPs loci, while it is still necessary to further promote the accuracy of the prediction model by screening more height-associated SNPs loci with population heterogeneity.

Innovative practice and popularization analysis of problem-based learning in the teaching of clinical molecular biology testing / 中华医学教育探索杂志

Objective To carry out innovative practice as well as questionnaire survey and conduct promotion analysis of clinical molecular biology testing based on problem-based learning (PBL). Methods 137 Students of medical laboratory technology discipline were chosen as subjects to conduct the innovative practice of PBL method. The teaching results were shared and promoted by video online through WeChat. Micro-questionnaire was conducted in 335 students, and the results of the survey were statistically analyzed. Result The improved PBL teaching based on speech contest can boost students to integrate into classroom teaching actively in which they had a better understanding of the knowledge so that the expected teaching quality of clinical molecular biology testing was achieved effectively. Questionnaire showed that the impact of PBL teaching method on students was not extensive currently, indicating that there was still more space to promoting such teaching methods. Although traditional teaching methods still held a place in students' minds (43.9%, 147 cases), the innovative teaching of PBL, which is novel, interesting and colorful, is more in line with the expectations of medical laboratory students in the new era and has the highest acceptance (49.6%, 166 cases). Conclusion The innovative practice of PBL teaching based on speech contest can achieve the purpose of strengthening students' knowledge acquisition and flexibility in the practical use of knowledge, which is worthy of promoting. Teachers could gradually integrate the new PBL teaching model into the tradi-tional teaching methods in the future, making students study efficiently in a relaxed and active atmosphere