Objective To analyze and compare the disease burden, trends, and influencing factors of lung cancer in adolescents and young adults (AYAs) in China and globally from 1990 to 2021, providing a reference for the prevention and treatment of lung cancer in China. Methods Indicators of lung cancer disease burden in different genders and age groups in 204 countries or regions from 1990 to 2021 were retrieved and standardized from GBD 2021 database. The Joinpoint regression model was used to calculate the average annual percentage change (AAPC) of the standardized rates of lung cancer in AYAs in China and globally from 1990 to 2021; changes in incidence, mortality, and disability-adjusted life years (DALYs) rates due to population growth, aging, and epidemiological changes were analyzed; differences in lung cancer disease burden in AYAs in different socio-demographic index (SDI) regions were analyzed; and the influencing factors of lung cancer in AYAs in China and globally were explored. Results From 1990 to 2021, the age-standardized incidence rate (ASIR) (AAPC=−0.18%, P<0.001), age-standardized mortality rate (ASMR) (AAPC=−0.62%, P<0.001), and age-standardized DALYs rate (AAPC=−0.62%, P<0.001) of lung cancer in AYAs in China showed a downward trend, consistent with the global trend, but the decline in China was relatively small. During this period, the age-standardized rates of various indicators of lung cancer in males in China and globally were higher than those in females, and the burden of lung cancer in Chinese males was heavier. However, due to the significant downward trend in males, the gap in lung cancer burden between males and females was narrowing. At the same time, from 2013 to 2021, the ASIR [annual percent change (APC)=2.01%, P<0.001], ASMR (APC=1.46%, P<0.001), and standardized DALYs rate (APC=1.46%, P<0.001) in China showed an upward trend. From 1990 to 2021, among the main influencing factors for the incidence, mortality, and DALYs rates of lung cancer in Chinese AYAs, the contribution of aging was upward-pushing, while the increase in global indicators was mainly attributed to population growth. The global burden of lung cancer in AYAs was overly concentrated in high SDI regions. Although the gap in lung cancer burden between high SDI and low SDI regions was narrowing, it remained widespread. Globally, smoking, environmental PM2.5, insufficient fruit intake, second-hand smoke, and indoor air pollution were prominent risk factors. Conclusion From 1990 to 2021, the global and Chinese AYAs lung cancer incidence and mortality rates generally show a downward trend, but the female lung cancer burden relatively increases, especially in young women without a history of smoking. Continued efforts are needed to reduce the burden of lung cancer in AYAs, especially the specific risk for young women.

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.
Humans ; Carcinoma, Hepatocellular/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; Caspase 3/metabolism* ; Liver Neoplasms/genetics* ; Molecular Docking Simulation ; Sincalide/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Hep G2 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

Objective: To investigate a SARS-CoV-2 epidemic reported in Rongcheng City, Weihai, Shandong Province. Methods: The SARS-CoV-2 nucleic acid positive patients and their close contacts were investigated, and the whole genome sequencing and genetic evolution analysis of 9 variant viruses were carried out. An infection source investigation and analysis were carried out from two sources of home and abroad, and three aspects of human, material and environment. Results: A total of 15 asymptomatic infections were reported in this epidemic, including 13 cases as employees of workshop of aquatic products processing company, with an infection rate of 21.67% (13/60). Two cases were infected people's neighbors in the same village (conjugal relation). The first six positive persons were processing workers engaged in the first process of removing squid viscera in the workshop of the company. The nucleic acid Ct value of the first time were concentrated between 15 and 29, suggesting that the virus load was high, which was suspected to be caused by one-time homologous exposure. The whole genome sequence of 9 SARS-CoV-2 strains was highly homologous, belonging to VOC/Gamma (Lineage P.1.15). No highly homologous sequences were found from previous native and imported cases in China. It was highly homologous with the six virus sequences sampled from May 5 to 26, 2021 uploaded by Chile. The infection source investigation showed that the company had used the squid raw materials captured in the ocean near Chile and Argentina from May to June 2021 over the last 14 days. Many samples of raw materials, products and their outer packages in the inventory were tested positive for nucleic acid. Conclusion: This epidemic is the first local epidemic caused by the VOC/Gamma of SARS-CoV-2 in China. It is speculated that the VOC/Gamma, which was prevalent in South America from May to June 2021, could be imported into China through frozen squid.
Humans ; SARS-CoV-2 ; COVID-19 ; Epidemics ; China/epidemiology*

Purpose: We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). Materials and Methods: A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. Results: The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. Conclusion Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction (XCD) based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion (MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke (IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis. We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis. Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids (SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Network Pharmacology ; Stroke/drug therapy*

【Objective】Platelet hyper- reactivity plays an important role in thrombosis and cardiovascular diseases. As a dietary supplement，Fruitflow，a water-soluble tomato concentrate，plays an important role in preventing cardiovascular diseases，but the mechanisms have been poorly understood，and there is no direct evidence about the effect of Fruitflow on thrombosis. This study intends to explore the effects of Fruitflow on platelet aggregation，activation and thrombosis in healthy people，and explore its possible mechanism.【Methods】Platelets from healthy men and women were incubated with different concentrations（0，20，40，80 mg/L）of Fruitflow，and the platelet aggregation was measured by platelet aggregometer. Platelet αIIbβ3 activation and fibrinogen binding to the activated platelets was measured by flow cytometry. The thrombosis in FeCl3- induced mesenteric artery thrombosis model in mice was observed by stereoscopic fluorescence microscope. The bleeding time was measured by tail clipping in mice. The total and phosphorylation levels of platelet Akt， Erk1/2 and JNK were determined by Western blotting.【Results】After the stimulation of ADP，Fruitflow could significantly attenuate platelet aggregation in the dose of 20，40，80 mg/L. Compared with that in the control group（43.75±5.91）%， platelet aggregation in the 80 mg/L group decreased to（8.25 ± 4.57）%（P < 0.000 1）. Fruitflow also inhibited the activation of platelet αIIbβ3. Compared with that in the control group（79.36±6.26），the platelet αIIbβ3 in the 80 mg/L group decreased to（65.79±5.73，P < 0.01）. Fruitflow reduced the platelet fibrinogen binding to the activated platelets. Compared with that in the control group（69.34 ± 6.63），platelet fibrinogen binding to the activated platelets in the 80 mg/L group decreased to（56.70±8.86，P < 0.05）. Fruitflow attenuated the thrombosis in FeCl3-induced mesenteric artery thrombosis model. Compared with that in the control group（22.50±4.86），the vessel occlusion in the 80 mg/L group was extended to（39.20 ± 4.61，P < 0.01）. There was no statistical difference between the control group （5.95 ± 0.69） and the 80 mg/L group（5.74 ± 0.76）in bleeding time（P > 0.05）. Fruitflow down- regulated the phosphorylation levels of platelet Akt， Erk1/2 and JNK proteins. Compared with the control group，P- Akt/Akt decreased from 0.97 ± 0.07 to 0.33 ± 0.13（P <0.001），P-Erk1/2/Erk1/2 decreased from 0.89±0.09 to 0.24±0.02（P < 0.01），and P-JNK/JNK decreased from 0.97±0.12 to 0.45±0.04（P < 0.01）in the 80 mg/L group.【Conclusion】Inhibition of platelet PI3K/Akt and MAPKs signaling pathway may be one of the mechanisms that Fruitflow inhibits platelet aggregation ，activation and thrombosis.

Objective To investigate the effect of the endoscopic surveillance system in irrigating fluid absorption and bleeding during transurethral resection of the prostate.Methods In vitro trials,we simulated the fluid absorption and bleeding in the operation by using self-developed endoscopic surveillance system from January 2013 to June 2013.Continuous irrigation of 5 ％ mannitol solution,we extracted 5 times irrigating fluid (each time 100 ml and a total of 500 ml) in the process of irrigation and recorded absorption measurements of every time extraction rinses.At the same time,we dripped human whole blood 5 times(each time 5 ml and a total of 25 ml) in the process of irrigation and recorded the bleeding measurements.The above process was repeated three times to detect the accuracy and consistency of the endoscopic surveillance system.In clinical trials,50 cases of BPH were monitored in surgery and the biochemical index,hemodynamics,irrigating fluid absorption and bleeding were compared from October 2016 to April 2017.The included criteria contained as follow:the age of patients should be more than 50 years.The transabdominal ultrasound showed that the volume of prostate should be more than 60 ml.The maximal uroflowmetry should be less than 15ml/s.The IPSS scores should be more than 8.Based on the operative time,two groups (＜60 min and ≥ 60 min) were classified.Results We developed the endoscopic surveillance system which is original in the world.In vitro trials,the average irrigating fluid were (100.60 ± 2.07) ml,(201.00±3.39) ml,(302.00±4.67) ml,(403.60±4.39) ml and (502.40 ±7.57) ml;and the average bleeding were (5.06 ± 0.11) ml,(10.10 ± 0.16) ml,(15.04 ± 0.15) ml,(20.06 ± 0.11) ml and (25.10 ± 0.16) ml.No significant difference was observed in all groups (P ＞ 0.05).In clinical trials,we compared some preoperative and postoperative indexes.The average blood oxygen saturation were (94.46 ± 2.49) ％ and (92.39 ± 2.77) ％ (P ＜ 0.01),the average Serum sodium ion concentration were (141.05 ± 2.52) mmol/L and (138.06 ± 4.27) mmol/L(P ＜ 0.01),the average HGB were (143.50 ± 13.43) g/L and (137.04 ± 14.25) g/L(P ＜ 0.01).The average HCT were (42.05 ± 4.09) ％ and (137.04 ± 14.25) ％ (P ＜ 0.01).The average HR were (77.9 ± 7.6) beats per minute and (77.93 ± 6.93) beats per minute (P＞0.05).The MAP were (90.32 ± 9.75) mmHg and (91.07±8.96)mmHg(P＞0.05).The average serum potassium ion concentration were (4.13 ± 0.53) mmol/L and (4.09 ± 0.37) mmol/L (P ＞ 0.05).The average irrigating fluid absorption of the group less than 60 minutes and the group equal or more than 60 minutes were (401.83 ± 279.23) ml and (885.25 ± 367.68) ml (P ＜ 0.01).The average blood loss were (64.10 ±47.47) ml and (158.40 ± 65.22) ml(P ＜0.01).The preoperative and postoperative hemodynamic,blood biochemical and hematology showed difference in our trials.Irrigating fluid absorption and blood loss were positively associated with operation time.Conclusions The endoscopic surveillance system was safety and accuracy.It can offer real-time monitoring data and alarm mechanism for the surgeons that possibly improve operation safety.

Objective: To explore the anti-lung cancer mechanism of Maimendong Tang and Qianjin Weijingtang (Jin Fang) by detecting the expression profiles of long noncoding RNA (lncRNA) and mRNA in mice tumor tissues of orthotopic Lewis lung cancer model. Method: C57BL/6 mice were randomly divided into normal group, model group and Jin Fang group (20 g·kg^-1·d^-1). After successful establishment of Lewis lung cancer model in situ in mice, Jin Fang was given orally the next day after treatment. Using gene chip technology, differential lncRNA and mRNA closely related with Jin Fang' s anti-lung cancer effect were detected, and cluster analysis was performed. The key lncRNA and mRNA were screened out by t-test and fold change of differential expression. Bioinformatic methods were used to predict target genes regulated by differential lncRNA, and functional and pathway analysis was performed. The histopathological technique was used to detect the differences in the tumor tissue of each group under light microscope. Result: lncRNA and mRNA chip hybridization results showed that Jin Fang regulated differential expressions of 887 lncRNA, in which 442 were up-regulated and 445 were down-regulated (P<0.05). There were 610 differential mRNA expressions, in which 376 were up-regulated and 234 were down-regulated(P<0.05). GO analysis showed that down-regulated or up-regulated target genes were mainly involved in biological processes (BP), such as cell metabolism regulation and signal pathway regulation. Molecular function (MF) analysis showed such functions DNA binding, protein binding, receptor binding and transcription factor activity in down-regulated or up-regulated target genes. Target genes were involved in multiple biological processes, cellular components and molecular functions. Signal pathway predictions indicated that Jin Fang can regulate the Janus kinase/signal transducer and activator of tran-ions(JAK/STAT) and other signaling pathways closely related to the development of lung cancer. The results of histopathological examination confirmed that Jin Fang could significantly improve the pathological changes of lung tissues in the mice compared with the model group. Conclusion: Jin Fang may exert its anti-lung cancer effect by regulating the expressions of multiple lncRNAs and mRNAs, and down-regulating related signaling pathways.

Background: Pulmonary Langerhans cell histiocytosis (PLCH) is an interstitial primary pulmonary disease, characterized by Langerhans cell proliferation. It is easily misdiagnosed in children. This study aimed to characterize the clinical manifestations and features of PLCH by retrospective analysis. Methods: A retrospective analysis was performed in 117 PLCH patients out of 338 LCH patients who were admitted in our center from November 2006 to October 2013. Variables between two groups were compared by Mann-Whitney U-test and Chi-square test. Kaplan-Meier curves were constructed to compare the survival rates and Cox regression to evaluate the effect of risk factors. Results: The median age of PLCH group was significantly lower than that of non-PLCH group (18.63 months vs. 43.4 months, P < 0.001). All PLCH children had other organ involvement and only 11 cases (9.4%) had respiratory symptoms. The most common radiologic finding was cystic lesions (29 cases, 24.8%). Pulmonary function abnormalities were dominated by obstructive ventilatory dysfunction (63 cases, 82.9%). The 5-year overall survival (OS) of PLCH children was 93.6% ± 2.3% and the event-free survival (EFS) was 55.7% ± 5.2%. Among the 38 cases with progressed or relapsed disease, five cases (13.2%) were due to progression or recurrence of lung damage. The 5-year OS of PLCH children with "risk organ" involvement was significantly lower than those without "risk organ" involvement (86.0% ± 4.9% vs. 100%, χ = 8.793, P = 0.003). The difference of EFS between two groups was also significant (43.7% ± 7.7% vs. 66.3% ± 6.5%, χ = 5.399, P = 0.020). The "risk organ" involvement had a significant impact on survival (hazard ratio = 1.9, P = 0.039). Conclusions PLCH mainly occurs in young children, and only a small percentage of patients have respiratory symptoms. They generally have other organ involvement. Most of PLCH children have a good prognosis and most lung lesions could have improved or stabilized. Management of "risk organ" involvement is the key point to improving EFS.
Child ; Child, Preschool ; Female ; Histiocytosis, Langerhans-Cell ; complications ; diagnosis ; Humans ; Infant ; Langerhans Cells ; Lung ; physiopathology ; Lung Diseases ; etiology ; Male ; Retrospective Studies

Background: Central nervous system (CNS) involvement is found in many patients with hemophagocytic lymphohistiocytosis (HLH). In this study, we mainly analyzed neurological symptoms, imaging findings, cerebrospinal fluid (CSF), and their relationship with outcomes of HLH children. Methods: Related data of 179 Chinese pediatric patients with HLH admitted to our center from January 2010 to December 2015 were analyzed retrospectively. Diagnosis and treatment were based on the HLH-2004 protocol. Two-tailed Chi-squared test was used to compare between different groups, and Kaplan-Meier survival curves were used to analyze the overall survival (OS) of patients with HLH. Results: In the present study, 21.2% (38/179) of total patients had neurological symptoms including seizure, irritability, somnolence, and unconsciousness. There were 80 (50.0%, excluding 19 patients without imaging data) patients with cranial imaging abnormalities. There were 14.7% (17/116, excluding 63 patients who did not accept lumbar puncture) of patients with abnormal CSF results. CNS involvement is defined as abnormalities in one or more of CNS symptoms, radiological findings, and CSF. Thus, 60.3% of them had CNS involvement. As for the prognosis, the median follow-up time was 3.2 years (17 lost to follow-up). The probable 3-year OS of children was higher without CNS involvement (86.0% ± 4.6%) than those with CNS involvement (68.9% ± 4.9%, hazard ratio [HR] = 2.286, P = 0.019). Among them, the probable 3-year OS of children without CNS symptoms was 76.0% ± 3.8%, higher than with CNS symptoms (59.5% ± 8.1%, HR = 2.147, P = 0.047). The 3-year OS of children with abnormal CSF was 64.7% ± 11.6%, compared with normal CSF (85.1% ± 3.7%, HR = 0.255, P = 0.038). Conclusions HLH patients with CNS involvement might have worse outcomes compared with those without CNS involvement, and CNS symptoms and CSF changes are more important to access the prognosis than imaging abnormality.
Central Nervous System Diseases ; etiology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lymphohistiocytosis, Hemophagocytic ; complications ; Male ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Seizures