Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

Objective: To examine the outcomes of Tiantan first-aid protocol on critically ill patients with primary central nervous system lymphoma (PCNSL). Methods: The clinical data of 18 patients with PCNSL who were treated according to Tiantan first-aid protocol at Department of Neurosurgery,Beijing Tiantan Hospital, Capital Medical University from November 2019 to December 2021 were retrospectively analyzed. There were 9 males and 9 females, aged (56.9±11.1)years (range: 29 to 77 years). The median Karnofsky performance status(KPS) score at admission was 40 (range: 20 to 60). Three patients were mild coma, 3 were lethargy and 12 were conscious. The mean midline shift was 0.7 cm (range: 0 to 1.8 cm). After admission, all patients were treated according to the plan of rapid biopsy, rapid routine pathology and rapid salvage chemotherapy. The treatment procedures, clinical and radiographic outcomes, KPS score and adverse reactions of patients after chemotherapy were collected. Results: All of the 18 patients completed the first-aid treatment. The median duration from admission to the biopsy was 1 day (range: 0 to 5 days), from biopsy to routine pathological diagnosis was 1 day (range: 1 to 4 days) and from routine pathology to salvage chemotherapy was 1 day (range: 0 to 4 days). All the patients were pathologically confirmed with diffuse large B cell lymphoma, 1 patient was double-hit lymphoma. Seventeen patients underwent clinical remission and 1 died of cardiac dysfunction. The successful salvage rate was 17/18. Radiologically, complete remission was observed in 1 case, partial remission in 16 cases, and stable disease in 1 case. The median KPS score at discharge was 60 (range: 30 to 80). The mild gastrointestinal, hematological and hepatic adverse effects were observed after chemotherapy. Conclusion: Tiantan first-aid protocol is effective for critically ill patients with PCNSL, which has the merit to be popularly used and improved.
Central Nervous System ; Central Nervous System Neoplasms/therapy* ; Critical Illness ; Female ; Humans ; Lymphoma/therapy* ; Male ; Retrospective Studies

OBJECTIVE: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). METHODS: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. RESULTS: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m²), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m²) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m²)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). CONCLUSION The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.
Cohort Studies ; Glomerulonephritis, IGA/pathology* ; Humans ; Kidney Failure, Chronic/therapy* ; Plasma Exchange ; Prognosis ; Retrospective Studies ; Steroids/therapeutic use*

According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 μmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.
Carboxylesterase/metabolism* ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions

Cephalotaxus is the only genus of Cephalotaxaceae family, and its natural resources are declining due to habitat fragmentation, excessive exploitation and destruction. In many areas of China, folk herbal doctors traditionally use Cephalotaxus plants to treat innominate swollen poison, many of which are cancer. Not only among Han people, but also among minority ethnic groups, Cephalotaxus is used to treat various diseases, e.g., cough, internal bleeding and cancer in Miao medicine, bruises, rheumatism and pain in Yao medicine, and ascariasis, hookworm disease, scrofula in She medicine, etc. Medicinal values of some Cephalotaxus species and compounds are acknowledged officially. However, there is a lack of comprehensive review summarizing the ethnomedicinal knowledge of Cephalotaxus, relevant medicinal phytometabolites and their bioactivities. The research progresses in ethnopharmacology, chemodiversity, and bioactivities of Cephalotaxus medicinal plants are reviewed and commented here. Knowledge gaps are pinpointed and future research directions are suggested. Classic medicinal books, folk medicine books, herbal manuals and ethnomedicinal publications were reviewed for the genus Cephalotaxus (Sanjianshan in Chinese). The relevant data about ethnobotany, phytochemistry, and pharmacology were collected as comprehensively as possible from online databases including Scopus, NCBI PubMed, Bing Scholar, and China National Knowledge Infrastructure (CNKI). "Cephalotaxus", and the respective species name were used as keywords in database search. The obtained articles of the past six decades were collated and analyzed. Four Cephalotaxus species are listed in the official medicinal book in China. They are used as ethnomedicines by many ethnic groups such as Miao, Yao, Dong, She and Han. Inspirations are obtained from traditional applications, and Cephalotaxus phytometabolites are developed into anticancer reagents. Cephalotaxine-type alkaloids, homoerythrina-type alkaloids and homoharringtonine (HHT) are abundant in Cephalotaxus, e.g., C. lanceolata, C. fortunei var. alpina, C. griffithii, and C. hainanensis, etc. New methods of alkaloid analysis and purification are continuously developed and applied. Diterpenoids, sesquiterpenoids, flavonoids, lignans, phenolics, and other components are also identified and isolated in various Cephalotaxus species. Alkaloids such as HHT, terpenoids and other compounds have anticancer activities against multiple types of human cancer. Cephalotaxus extracts and compounds showed anti-inflammatory and antioxidant activities, immunomodulatory activity, antimicrobial activity and nematotoxicity, antihyperglycemic effect, and bone effect, etc. Drug metabolism and pharmacokinetic studies of Cephalotaxus are increasing. We should continue to collect and sort out folk medicinal knowledge of Cephalotaxus and associated organisms, so as to obtain new enlightenment to translate traditional tips into great therapeutic drugs. Transcriptomics, genomics, metabolomics and proteomics studies can contribute massive information for bioactivity and phytochemistry of Cephalotaxus medicinal plants. We should continue to strengthen the application of state-of-the-art technologies in more Cephalotaxus species and for more useful compounds and pharmacological activities.

Nonalcoholic fatty liver disease (NAFLD) is regarded as the most common liver disease with no approved therapeutic drug currently. Silymarin, an extract from the seeds of Silybum marianum, has been used for centuries for the treatment of various liver diseases. Although the hepatoprotective effect of silybin against NAFLD is widely accepted, the underlying mechanism and therapeutic target remain unclear. In this study, NAFLD mice caused by methionine-choline deficient (MCD) diet were orally administrated with silybin to explore the possible mechanism and target. To clarify the contribution of peroxisome proliferator-activated receptor α (PPARα), PPARα antagonist GW6471 was co-administrated with silybin to NAFLD mice. Since silybin was proven as a PPARα partial agonist, the combined effect of silybin with PPARα agonist, fenofibrate, was then evaluated in NAFLD mice. Serum and liver samples were collected to analyze the pharmacological efficacy and expression of PPARα and its targets. As expected, silybin significantly protected mice from MCD-induced NAFLD. Furthermore, silybin reduced lipid accumulation via activating PPARα, inducing the expression of liver cytosolic fatty acid-binding protein, carnitine palmitoyltransferase (Cpt)-1a, Cpt-2, medium chain acyl-CoA dehydrogenase and stearoyl-CoA desaturase-1, and suppressing fatty acid synthase and acetyl-CoA carboxylase α. GW6471 abolished the effect of silybin on PPARα signal and hepatoprotective effect against NAFLD. Moreover, as a partial agonist for PPARα, silybin impaired the powerful lipid-lowering effect of fenofibrate when used together. Taken together, silybin protected mice against NAFLD via activating PPARα to diminish lipid accumulation and it is not suggested to simultaneously take silybin and classical PPARα agonists for NAFLD therapy.

Purpurolides D-F (1-3), three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system, were isolated from the endophytic fungus Penicillium purpurogenum IMM 003. Their structures were unambiguously elucidated based on extensive spectroscopic data analyses, C NMR chemical shifts calculations coupled with the DP4+ probability method, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compounds 1-3 showed significant inhibitory activity against pancreatic lipase (PL). The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.

ObjectiveTo investigate the drug-resistant gene polymorphisms in Plasmodium falciparum imported from Equatorial Guinea to Shandong Province. MethodsFrom 2015 to 2016, blood samples were collected from imported P. falciparum malaria patients returning from Equatorial Guinea to Shandong Province, and genome DNA of the malaria parasite was extracted. The drug-resistant Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum were amplified using a PCR assay, followed by DNA sequencing, and the sequences were aligned. Results The target fragments of all 5 drug-resistant genes of P. falciparum were successfully amplified and sequenced. There were 72.8%, 18.6%, and 8.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfcrt gene, respectively, and all mutant haplotypes were CVIET (the underline indicates the mutation site). There were 20.0%, 61.4% and 18.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfmdr1 gene, respectively, and the mutant haplotypes mainly included YF and NF (the underlines indicate the mutation sites). There were 1.4%, 98.6%, and 0 of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhfr gene, respectively, and AIRNI was the predominant mutant haplotype (the underline indicates the mutation site). There were 1.4%, 94.3%, and 4.3% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhps gene, respectively, and SGKAA was the predominant mutant haplotype (the underline indicates the mutation site). The complete drug-resistant IRNGE genotype consisted of 8.6% of the Pfdhfr and Pfdhps genes, and the K13 gene A578S mutation occurred in 1.4% of the parasite samples. Conclusions There are mutations in the Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum imported from Equatorial Guinea to Shandong Province, with a low frequency in the Pfcrt gene mutation and a high frequency in the Pfmdr1, Pfdhfr, and Pfdhps gene mutations, and the K13 gene A578S mutation is detected in the parasite samples.

OBJECTIVE: To study the clinical features of neuroblastoma (NB) and the factors influencing survival rate. METHODS: A total of 44 children with NB who were admitted from April 2016 to February 2020 were enrolled as research subjects. A retrospective analysis was performed on their medical data and follow-up data. RESULTS: The common clinical symptoms of these 44 children were fever (10/44, 23%), mass (9/44, 20%), abdominal pain (8/44, 18%), cough (7/44, 16%), pale complexion (3/44, 7%), claudication (2/44, 5%), and abnormal activity (2/44, 5%). According to the INSS stage, 2 children (4%) had stage I NB, 5 children (11%) had stage II NB, 5 children (11%) had stage III NB, and 32 children (73%) had stage IV NB. The mean follow-up time was (15.3±1.5) months, with a recurrence rate of 20% and an overall survival rate of 82%. Among the 44 children, 29 (66%) achieved event-free survival and 7 (16%) had survival with tumor. The univariate analysis showed that a pathological type of NB and an increase in serum neuron-specific enolase (NSE) decreased the overall survival rate of children with NB (P<0.05). CONCLUSIONS The clinical symptoms of children with NB are not specific at the first visit. Fever, abdominal pain, and mass are common symptoms, and there is a high proportion of children in the advanced stage. The pathological type of NB and an increase in serum NSE may be associated with a reduction in the overall survival rate of children with NB.
Child ; Humans ; Infant ; Infant, Newborn ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neuroblastoma ; Phosphopyruvate Hydratase ; Retrospective Studies ; Survival Rate

Pancreatic cancer is the most common digestive tract tumor with an increasing incidence in recent years. The poor prognosis of pancreatic cancer is mainly because of the inability of detecting tumor at an early stage,its high potential for early dissemination,and its relatively poor sensitivity to chemotherapy. Most patients have lost the opportunity for surgery when they are diagnosed,which resulted in an urgent need for the development of more effective and safe therapies for pancreatic cancer. However,the current clinical cancer chemotherapy based on gemcitabine leads to poor prognosis in pancreatic patients. With the continuous research on the biological and cellular signaling pathways of pancreatic cancer,there have emerged a great many of novel agents,including new chemotherapeutic,targetable and immune-modulatory drugs,and some drugs have achieved encouraging results. Furthermore,as an alternative and supplementary method,traditional Chinese medicine has shown good application prospects in the field of pancreatic cancer treatment. This article reviews the current status of drug therapy for pancreatic cancer,summarizes the strength and weakness of existing therapeutic drugs in the application process,gives prospects of possible breakthroughs for the pharmacotherapy in the future,and provides certain new ideas and lessons for subsequent drug development.
Forecasting ; Humans ; Medicine, Chinese Traditional ; Pancreatic Neoplasms ; drug therapy