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Background Dihydropyrimidinase like 2 (DPYSL2) has been linked to tumor metastasis. However, the function of DPSY2L in lung adenocarcinoma (LUAD) is yet to be explored. Methods Herein, we assessed DPYSL2 expression in various tumor types via online databases such as Oncomine and Tumor Immune Estimation Resource (TIMER). Further, we verified the low protein and mRNA expressions of DPYSL2 in LUAD via the ULCAN, The TCGA and GEPIA databases. We applied the ROC curve to examine the role of DPYSL2 in diagnosis. The prognostic significance of DPYSL2 was established through the Kaplan–Meier plotter and the Cox analyses (univariate and multivariate). TIMER was used to explore DPYSL2 expression and its connection to immune infiltrated cells. Through Gene Set Enrichment Analysis, the possible mechanism of DPYSL2 in LUAD was investigated. Results In this study, database analysis revealed lower DPYSL2 expression in LUAD than in normal tissues. The ROC curve suggested that expression of DPYSL2 had high diagnostic efficiency in LUAD. The DPYSL2 expression had an association with the survival time of LUAD patients in the Kaplan–Meier plotter and the Cox analyses. The results from TIMER depicted a markedly positive correlation of DPYSL2 expression with immune cells infiltrated in LUAD, such as macrophages, dendritic cells, CD4+ T cells, and neutrophils. Additionally, many gene markers for the immune system had similar positive correlations in the TIMER analysis. In Gene Set Enrichment Analysis, six immune-related signaling pathways were associated with DPYSL2. Conclusions In summary, DPYSL2 is a novel biomarker with diagnostic and prognostic potential for LUAD as well as an immunotherapy target. Highlights Expression of DPYSL2 was considerably lower in LUAD than in normal tissues. Investigation of multiple databases showed a high diagnostic value of DPYSL2 in LUAD. DPYSL2 can independently predict the LUAD outcomes. Immune-related mechanisms may be potential ways for DPYSL2 to play a role in LUAD.

ObjectivesPseudohypoparathyroidism (PHP) is a rare disease, especially when combined with pregnancy. We aimed to explore the changes in serum calcium/parathyroid hormone (PTH) level and medical treatment in a case series of PHP during pregnancy and the postpartum period.MethodsA total of five PHP patients with six pregnancies were enrolled. The classification of PHP was based on (epi)genetic analysis. Clinical characteristics, biochemical indices, and treatment strategies before, during, and after pregnancy were retrospectively collected.ResultsAll patients received calcium and vitamin D agents with nearly normal serum calcium before pregnancy except patient 2 who was found hypocalcemic during gestation. All patients chose Cesarean section, and one suffered preterm delivery due to oligoamnios. The neonatal birth weight ranged from 2,250 to 4,300 g, and all neonates were free of hypocalcemia-related symptoms. The change in calcium metabolism was inconsistent including stable, improved, or worsened during pregnancy. Serum PTH level remained low in the first two trimesters in patients with stable and improved conditions while increased in the last two trimesters in patients with a worsened condition. Serum calcium changed inconsistently while PTH increased consistently during lactation. For patients who did not breastfeed, calcium homeostasis improved after delivery.ConclusionCalcium homeostasis and medicine dosage changed differently in PHP patients during pregnancy and lactation. However, most patients had good pregnancy outcomes. Serum PTH levels might predict changes in calcium metabolism during pregnancy.

Background Our previous study reported that recombinant human epidermal growth factor (rhEGF)-triggered EGFR internalization promoted radioresistance. Here, we aimed to evaluate the effect of rhEGF on the skin protection of rectal and anal cancer patients receiving radiotherapy. Methods One hundred and ninety-three rectal and anal cancer patients who received radiotherapy were prospectively enrolled from January 2019 to December 2020. To perform self-controlled study, the left and right pelvic skin area (separated by midline) were randomly assigned to the rhEGF and control side. The association between radiation dermatitis and factors including rhEGF, the dose of radiotherapy and tumor distance from anal edge were analyzed. Results Among 193 enrolled patients, 41 patients (21.2%) did not develop radiation dermatitis, and 152 patients (78.8%) suffered radiation dermatitis on at least one side of pelvic skin at the end of radiotherapy. For the effect on radiation dermatitis grade, rhEGF had improved effect on 6 (4.0%) patients, detrimental effect on 2 (1.3%) patients, and no effect on 144 (94.7%) patients. Whereas for the effect on radiation dermatitis area, rhEGF showed improved effect on the radiation dermatitis area of 46 (30.2%) patients, detrimental effect on 15 (9.9%) patients, and no effect on 91 (59.9%) patients. The radiation dermatitis area of rhEGF side was significantly smaller than that of control side (P = 0.0007). Conclusions rhEGF is a skin protective reagent for rectal and anal cancer patients receiving radiotherapy. Trial registration Chinese Clinical Trial Registry identifier: ChiCTR1900020842; Date of registration: 20/01/2019.

The big brand of Chinese patent medicine, Fufang Danshen Prescription(FDP), effective in promoting blood circulation, resolving blood stasis, regulating qi, and relieving pain, is wide in clinical application and diverse in dosage forms and products, but its quality and price are uneven, which causes problems for doctors and patients. To clarify the key links and weakness of quality control leading to the quality difference of FDP products, the present study carried out a comprehensive evaluation of the whole production cycle of FDP based on thequot;high-quality Chinese patent medicine evaluation criteriaquot; and analyzed the advantages and disadvantages of production and quality of different FDP products according to scores. The results showed that the scores of various products in thequot;raw materials selectionquot; varied greatly. The highest score(S1) and the lowest score(S2) differed by more than 3 times, indicating that different manufacturers had inconsistent requirements for the selection of raw materials, leading to fundamental differences in the quality of raw materials. The scores in thequot;production processquot; varied slightly, with an average score of 66.8%. The manufacturer S8 obtained the highest score(84.0%), which indicated the emergence of intelligent manufacturing production. The scores(with the average score of 44.0%) in thequot;quality controlquot; were lower than those of the previous two items, which was attributed to the fact that most FDP products only met thequot;qualifiedquot; benchmark required by the 2020 edition of Chinese Pharmacopoeia, and their consistency and high quality were both uncontrollable. The scores in thequot;post-marketing researchquot; were the lowest(with an average score of 28.5%), and most manufacturers were scored 0, which reflected little attention paid. Only a few brand manufacturers were scored acceptably and they were willing to carry out relevant research on post-marketing evaluation. The evaluation results demonstrated the key links and weakness leading to the production and quality differences of FDP from different manufacturers. It is expected to improve the quality of FDP, promote the formation of thequot;high quality and good pricequot; mechanism, and provide information for the centralized procurement of governments.

To study the chemical constituents from the ripe fresh fruits of

Cefprozil, an oral second-generation semi-synthetic cephalosporin, possesses a broad spectrum of antimicrobial activity. A granule formulation has been developed to improve medication adherence of the patients. This study was conducted to assess the bioequivalence of the granule formulation to a dry suspension in healthy Chinese volunteers and estimate the pharmacokinetic (PK) profiles of cefprozil. An open-label, randomized, single-dose, two-period, two-group, crossover study was conducted in 60 healthy Chinese volunteers under fasted or fed conditions (30 volunteers for each condition) to assess the bioequivalence between two formulations of cefprozil. Blood samples were collected at specified time intervals, and the plasma concentrations of cis- and trans-cefprozil were determined by a validated liquid chromatography-tandem mass spectrometry (LC–MS/MS) method. PK and bioavailability parameters were estimated via non-compartmental methods. Adverse events (AEs) were also recorded. Under fasted conditions, the mean Cmax was (3534.70 ± 634.67) ng/ml, Tmax was (0.98 ± 0.25) h, t1/2 was (1.37 ± 0.13) h and AUC0-t was (9302.86 ± 1618.39) ng·h/ml, respectively, after a single dose of 125 mg cefprozil for suspension. Under fed conditions, the mean Cmax was (2438.80 ± 493.78) ng/ml, Tmax was (1.66 ± 0.76) h, t1/2 was (1.36 ± 0.24) h and AUC0-t was (9332.36 ± 1373.61) ng·h/ml, respectively. The PK parameters of the granule formulation of cefprozil were similar to those of the suspension. The 90% CI values of the GMRs of Cmax, AUC0-t and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence range (80.00–125.00%). According to the criteria for bioequivalence, the test granule formulations of cefprozil and "Cefprozil for Suspension®" were determined to be bioequivalent whether under fasted or fed conditions by measurement of cis-, trans- and total cefprozil. ClinicalTrials.gov identifier, NCT04414254.

SHR6390 is a new developed highly effective and selective small-molecule oral CDK4/6 inhibitor. We aimed to evaluate the effect of food on the pharmacokinetics of SHR6390 tablets.In an open-label two-way crossover study, 24 healthy Chinese volunteers were randomly divided into Group A and Group B, and 12 volunteers in each group received a single oral dose of a SHR6390 150-mg tablet under fasting and high-fat conditions. Blood samples were collected and determined for pharmacokinetic analyses. A liquid chromatography-tandem mass spectrometry method was developed and validated for determining the SHR6390 concentration.The time to maximum plasma concentration was not significantly affected by a high-fat diet. Compared with the fasting group, maximum plasma concentration, i.e., the area under the concentration-time curve (AUCFood intake increased the maximum plasma concentration, AUC

Purpose The combination of lisinopril and amlodipine has a marked additional effect on blood pressure and fewer side effects than individual monotherapy. This study was conducted to compare the pharmacokinetic parameters and evaluate the bioequivalence between two Lisinopril/amlodipine tablets in healthy Chinese subjects. Methods A single center, randomized, open-label, single-dose, two-period crossover bioequivalence study was designed in healthy Chinese subjects under both fasting and fed conditions. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 24, 36, 48, 72, 96, 144, 168 h after administration. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was applied to determine the plasma concentration of lisinopril and amlodipine. Maximum concentration (Cmax) and area under the concentration–time curve (AUC) were used to evaluate bioequivalence. Adverse events were recorded. Results Ninety-two healthy subjects were enrolled, and 75 completed the study. The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ of lisinopril and amlodipine under both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80–1.25. A high-fat meal appeared to decrease the Cmax and AUC of lisinopril. No severe adverse events were observed. Conclusion The trial demonstrated that the test and the reference lisinopril/amlodipine tablets were bioequivalent and well tolerated in Chinese people under fasting and fed conditions. Trial registration Clinical Trails.gov identifier, NCT04885660 (retrospectively registered in 13/05/ 2021).

Two unusual phenanthrene derivatives related to aporphine alkaloids, artapilosines A (

Clausena lansium, also known as wampee, is a species of strongly scented evergreen trees belonging to the genus Clausena (Rutaceae), which is native to southern China. Its ripe fruits have been consumed as a very popular fruit and reported to possess a range of biological activities. To study the potential health-promoting constituents from the fruits of C. lansium, a chemical investigation on its fruits was thus carried out. In this study, 16 carbazole alkaloids (1-16), including six new carbazole alkaloids, clausenalansines A-F (1-6), were separated from the fruits of C. lansium. The molecular structures of these isolated new carbazole alkaloids (1-6) were ambiguously established on the basis of comprehensive spectroscopic methods. The known analogues (7-16) were determined via comparing their experimental data with those described in the literature, which were separated from C. lansium for the first time. All these isolated alkaloids were tested in vitro for their neuroprotective effects against 6-hydroxydopamine induced cell death in human neuroblastoma SH-SY5Y cells. Carbazole alkaloids 1-16 displayed remarkable neuroprotective effects possessing the EC50 values ranging from 0.36 ± 0.02 to 10.69 ± 0.15 μM. These findings indicate that regular consumption of the fruits of C. lansium may help people prevent the occurrence of Parkinson's disease. In addition, the separation and identification of these carbazole alkaloids possessing remarkable neuroprotective effects from the fruits of C. lansium could be extremely important to the discovery of new agents for the prevention and treatment of Parkinson's disease.

Ficus carica is an Asian species of flowering plant belonging to the genus Ficus of the family Moraceae, native to Western Asia and the Middle East. Its fruits, usually known as common fig or fig, have been consumed as a very popular health-promoting fruit worldwide since ancient times. To investigate the potential health-promoting chemical constituents of the fruits of F. carica, a systematic phytochemical study on its fruits was therefore carried out. In our study, four new structurally diverse prenylated isoflavone derivatives, ficucaricones A-D (1-4), along with 12 known analogues (5-16) were separated from the fruits of F. carica. Their chemical structures were ambiguously elucidated based on extensive spectroscopic methods. The anti-inflammatory effects and antiproliferative activities of these isolated prenylated isoflavone derivatives were tested. Prenylated isoflavone derivatives (1-16) displayed remarkable inhibitory effects against nitric oxide (NO) production with the IC50 values ranging from 0.89 ± 0.05 to 8.49 ± 0.18 μM, comparable to that of the positive control (hydrocortisone). Furthermore, compounds 1-16 also exhibited pronounced antiproliferative activities against diverse human cancer cell lines in vitro, holding the IC50 values ranging from 0.18 ± 0.03 to 18.76 ± 0.09 μM. These findings indicate that regular consumption of the fruits of F. carica may help to prevent the occurrence of inflammatory diseases and tumors. Moreover, the isolation and characterization of these prenylated isoflavone derivatives possessing remarkable anti-inflammatory effects and antiproliferative activities could be meaningful to the discovery of new anti-inflammatory and antitumor agents.

A chemical study on the stems and leaves of

Beryllium and its compounds are systemic toxicants that are widely applied in many industries. Hydrogen sulfide has been found to protect cells. The present study aimed to determine the protective mechanisms involved in hydrogen sulfide treatment of 16HBE cells following beryllium sulfate-induced injury. 16HBE cells were treated with beryllium sulfate doses ranging between 0 and 300 μM BeSO4 . Additionally, 16HBE cells were subjected to pretreatment with either a 300 μM dose of sodium hydrosulfide (a hydrogen sulfide donor) or 10 mM DL-propargylglycine (a cystathionine-γ-lyase inhibitor) for 6 hr before then being treated with 150 μM beryllium sulfate for 48 hr. This study illustrates that beryllium sulfate induces a reduction in cell viability, increases lactate dehydrogenase (LDH) release, and increases cellular apoptosis and autophagy in 16HBE cells. Interestingly, pretreating 16HBE cells with sodium hydrosulfide significantly reduced the beryllium sulfate-induced apoptosis and autophagy. Moreover, it increased the mitochondrial membrane potential and alleviated the G2/M-phase cell cycle arrest. However, pretreatment with 10 mM DL-propargylglycine promoted the opposite effects. PI3K/Akt/mTOR and Nrf2/ARE signaling pathways are also activated following pretreatment with sodium hydrosulfide. These results indicate the protection provided by hydrogen sulfide in 16HBE cells against beryllium sulfate-induced injury is associated with the inhibition of apoptosis and autophagy through the activation of the PI3K/Akt/mTOR and Nrf2/ARE signaling pathways. Therefore, hydrogen sulfide has the potential to be a promising candidate in the treatment against beryllium disease.

Avoiding the tragedy of the commons requires altruists to incur some losses to benefit the group. Although specific rules and self-enforcing agreements could help maintain the cooperation system stable, the costly recognition and free-rider problem are still questioned these two cooperation maintenance mechanisms. We here considered the situation of both exit costs and exit benefits in the asymmetric prisoner's dilemma game and introduced a super-rational aspiration induced strategy updating, where players adjust strategies in line with their payoffs and aspirations. If their payoffs reach or exceed the aspiration levels, which may be rational or super-rational, they keep their strategies. Otherwise, they imitate a local neighbor's strategy. We explored this rule in the structured and well-mixed population. The results show that super-rationality and asymmetry could together promote cooperation when exit costs exist. With exit benefit, super-rationality promotes cooperation in both structures and asymmetry only works in the well-mixed population. This suggests that the introduced strategy updating rule could sustain cooperation among egoists with exit rights.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 called for innovation in addressing age-related disabilities. Our study aimed to identify and validate a urinary peptidomic profile (UPP) differentiating healthy from unhealthy ageing in the general population, to test the UPP predictor in independent patient cohorts, and to search for targetable molecular pathways underlying age-related chronic diseases. METHODS: In this prospective population study, we used data from participants in the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO), done in northern Belgium from 1985 to 2019, and invited participants to a follow-up examination in 2005-10. Participants were eligible if their address was within 15 km of the examination centre and if they had not withdrawn consent in any of the previous examination cycles (1985-2004). All participants (2005-10) were also invited to an additional follow-up examination in 2009-13. Participants who took part in both the 2005-10 follow-up examination and in the additional 2009-13 follow-up visit constituted the derivation dataset, which included their 2005-10 data, and the time-shifted internal validation dataset, which included their 2009-13 data. The remaining participants who only had 2005-10 data constituted the synchronous internal validation dataset. Participants were excluded from analyses if they were incapacitated, had not undergone UPP, or had either missing or outlying (three SDs greater than the mean of all consenting participants) values of body-mass index, plasma glucose, or serum creatinine. The UPP was assessed by capillary electrophoresis coupled with mass spectrometry. The multidimensional UPP signature reflecting ageing was generated from the derivation dataset and validated in the time-shifted internal validation dataset and the synchronous validation dataset. It was further validated in patients with diabetes, COVID-19, or chronic kidney disease (CKD). In FLEMENGHO, the mortality endpoints were all-cause, cardiovascular, and non-cardiovascular mortality; other endpoints were fatal or non-fatal cancer and musculoskeletal disorders. Molecular pathway exploration was done using the Reactome and Kyoto Encyclopedia of Genes and Genomes databases. FINDINGS: 778 individuals (395 [51%] women and 383 [49%] men; aged 16·2-82·1 years; mean age 50·9 years [SD 15·8]) from the FLEMENGHO cohort had a follow-up examination between 2005 and 2010, of whom 559 participants had a further follow-up from Oct 28, 2009, to March 19, 2013, and made up the derivation (2005-10) and time-shifted internal validation (2009-13) datasets. 219 were examined once and constituted the synchronous internal validation dataset (2005-10). With correction for multiple testing and multivariable adjustment, chronological age was associated with 210 sequenced peptides mainly showing downregulation of collagen fragments. The trained model relating chronological age to UPP, derived by elastic net regression, included 54 peptides from 17 proteins. The UPP-age prediction model explained 76·3% (r=0·87) of chronological age in the derivation dataset, 54·4% (r=0·74) in the time-shifted validation dataset, and 65·3% (r=0·81) in the synchronous internal validation dataset. Compared with chronological age, the predicted UPP-age was greater in patients with diabetes (chronological age 50·8 years [SE 0·37] vs UPP-age 56·9 years [0·30]), COVID‑19 (53·2 years [1·80] vs 58·5 years [1·67]), or CKD (54·6 years [0·97] vs 62·3 years [0·85]; all p

Beryllium and its compounds are systemic toxicants that mainly accumulate in the lungs. As a regulator of gene expression, microRNAs (miRNAs) were involved in some lung diseases. This study aimed to analyze the levels of some inflammatory cytokine and the differential expressions of miRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4 ) and to further explore the biological functions of differentially expressed miRNAs. The profile of miRNAs in 16HBE cells was detected using the high-throughput sequencing between the control groups (n = 3) and the 150 μmol/L of BeSO4 -treated groups (n = 3). Bioinformatics analysis of differentially expressed miRNAs was performed, including the prediction of target genes, Gene Ontology (GO) analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify some damage-related miRNAs. We found that BeSO4 can increase the levels of some inflammatory cytokine such as interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). And BeSO4 altered miRNAs expression of 16HBE cells and a total of 179 differentially expressed miRNAs were identified, including 88 upregulated miRNAs and 91 downregulated miRNAs. The target genes predicted by 28 dysregulated miRNAs were mainly involved in the transcription regulation, signal transduction, MAPK, and VEGF signaling pathway. The qRT-PCR verification results were consistent with the sequencing results. miRNA expression profiling in 16HBE cells exposed to BeSO4 provides new insights into the toxicity mechanism of beryllium exposure.

The phytochemical investigation on the fruits of Clausena anisum-olens led to the isolation of 18 carbazole alkaloids (1–18), containing three new ones, clausenanisines A–C (1–3), and three new naturally occurring carbazole alkaloids, clausenanisines D–F (4–6), as well as 12 known analogues (7–18). The chemical structures of clausenanisines A–F (1–6) were elucidated by extensive spectroscopic methods. Notably, clausenanisine A (1) was a novel carbazole alkaloid with a unique five-membered cyclic ether, while clausenanisine E (5) is an unusual carbazole alkaloid owning an unprecedented naturally occurring carbon skeleton possessing 14 carbon atoms. The known carbazole alkaloids (7–18) were identified by the comparison of their spectral data with those data reported in the literature. All known carbazole alkaloids 7–18 were isolated from C. anisum-olens for the first time. Moreover, all isolated compounds 1–18 were assessed for their protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities in vitro. Compounds 1–18 exhibited remarkable PTP1B inhibitory activities with IC50 values in the range of 0.58 ± 0.05 to 38.48 ± 0.32 μM, meanwhile, compounds 1–18 displayed significant α-glucosidase inhibitory activities with IC50 values ranging from 3.28 ± 0.16 to 192.23 ± 0.78 μM. These research results imply that the separation and identification of these carbazole alkaloids showing notable PTP1B and α-glucosidase inhibitory activities from the fruits of C. anisum-olens can be very significant for discovering and developing new PTP1B inhibitors and α-glucosidase inhibitors for the treatment of diabetes mellitus.

This study aims to identify differentially expressed microRNAs (miRNAs) in gastric cancer by comparing gastric cancerous tissues with normal tissues, explore the potential roles. The miRNA expression microarray was employed on gastric cancer tissues, and apparently normal para-cancerous tissues from 3 patients undergoing radical surgery were matched. Quantitative RT-PCR was performed on the other 7 patients to validate the findings of the microarray. Furthermore, Gene Ontology (GO) analysis and enrichment analysis of KEGG Pathway were performed for 5 dysregulated candidate miRNAs, including 3 upregulated (miR-31-3p, miR-6736-3p, and miR-147b) and 2 downregulated (miR-3065-5p and miR-3921) miRNAs, in order to determine the role of miRNAs in tumorigenesis and development. Among these miRNAs, 17 miRNAs were found to be upregulated, and 19 miRNAs were found to be downregulated. The dysregulated expression of 5 candidate miRNAs, including miR-31-3p, miR-147b, miR-6736-3p, miR-3065-5p, and miR-3921, were verified by quantitative RT-PCR in the validation set. Among these miRNAs, miR-31-3p, miR-6736-3p, miR-3065-5p, and miR-3921 had 551 target gene intersections. The GO and KEGG Pathway analyses Revealed that miR-31-3p, miR-6736-3p, miR-3065-5p, and miR-3921 may participate in multiple pathophysiological processes, such as foreign substance metabolism and chemical carcinogenesis. The profile of differentially expressed miRNAs was successfully screened, and 4 miRNAs (i.e., miR-31-3p, miR-6736-3p, miR-3065-5p, and miR-3921) appeared to be involved in gastric carcinogenesis. These might serve as promising biomarkers for gastric cancer.

Two novel γ-lactone derivatives, trigoheterophines A (1) and B (2), together with four known furan derivatives (3–6), were isolated from the stems and leaves of Trigonostemon heterophyllus. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparing with the data reported in literature. Among them, trigoheterophines A (1) and B (2) represent an unusual type of γ-lactone derivatives, possessing 21 carbon atoms on the carbon skeleton, and known compouds (3–6) are rare furan derivatives in the plant kingdom with diverse long-chain hydrocarbyl groups as substituents at C-4. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1–6 showed significant antiproliferative effects against various human cancer cell lines with IC50 values ranging from 0.28 to 12.06 μM. These findings suggest that the discoveries of these novel γ-lactone derivatives and furan derivatives with significant antiproliferative activities isolated from T. heterophyllus could be of great importance to the development of new anticancer agents.

A novel tetrahydrofuran derivative, trigonohowine (1), together with five known tetrahydrofuran derivatives (2–6), were isolated from the stems and leaves of Trigonostemon howii. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. Among them, trigonohowine (1) represents the first example of a new type of tetrahydrofuran derivative, possessing an unprecedented carbon skeleton containing 23 carbon atoms on the carbon skeleton and the known compouds (2–6) are rare tetrahydrofuran derivatives in the plant kingdom with various carbon skeletons. All isolated compounds were evaluated for their anti-HIV-1 activities. Compounds 1–6 showed significant anti-HIV-1 activities with EC50 ranged from 0.08 to 1.03 µM. These findings suggest that the discoveries of these tetrahydrofuran derivatives with significant anti-HIV-1 activities isolated from T. howii could be of great importance to the development of new anti-HIV agents.

Phytochemical investigation on the stems and leaves of Trigonostemon howii resulted in the isolation of a new abietane diterpenoid, trigohowimine A (1), along with seven known structurally diverse diterpenoids (2-8). The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparison with data reported in the literature. New compound 1 was evaluated for its cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480. Compound 1 showed significant inhibitory effects against various human cancer cell lines with IC50 values ranging from 0.82 to 8.53 μM.

Three new dihydrobenzofuran neolignans, mappiodoinins A-C ( 1 - 3 ), together with nine known analogues ( 4 - 12 ) were isolated from the stems and leaves of Mappianthus iodoies . Their structures with the absolute configurations were elucidated by extensive spectroscopic methods. This is the first time to find dihydrobenzofuran neolignans from the genus Mappianthus. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW-480 in vitro . Neolignans 1 - 12 showed significant cytotoxic effects against various human cancer cell lines with IC 50 values ranging from 0.16 to 18.62 μM.

A new indole alkaloid, nauclorienine (1), along with seven known alkaloids (2–8), were isolated from the stems and leaves of Nauclea orientalis. Among them, nauclorienine (1) was a new indole alkaloid holding a rare corynanthe-type skeleton, and the known compounds (2–8) were isolated from N. orientalis for the first time. Their structures were elucidated on the basis of extensive spectroscopic data analyses. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Alkaloids 1–4 exhibited significant inhibitory effects against various human cancer cell lines with IC50 values comparable to those of cisplatin.

Two new prenylated chromones, artoheterophines A (1) and B (2), five known prenylated chromones (3–7), as well as five known biogenetically related prenylated flavonoids (8–12) were isolated and characterized from the stems and leaves of A. heterophyllus. Their chemical structures were unambiguously determined through comprehensive spectral data analyses. The antiproliferative and anti-inflammatory effects of all these isolated prenylated chromones and flavonoids were evaluated in vitro. As a result, compounds 1–12 showed notable inhibitory effects against various human cancer cell lines with IC50 values ranging from 0.36 ± 0.02 to 22.09 ± 0.16 μM. Meanwhile, compounds 1–12 exhibited significant inhibitory activities on nitric oxide (NO) production holding IC50 values in the range of 0.48 ± 0.05–19.87 ± 0.21 µM. These research results suggest that the isolation and characterization of these prenylated chromones (1–7) and flavonoids (8–12) holding significant antiproliferative and anti-inflammatory activities could be significant to the discovery and development of new natural anti-tumor and anti-inflammatory drugs. The findings also provides a phytochemical evidence for further development and utilization of the stems and leaves of A. heterophyllus in health and pharmaceutical products.

The chemical constituents from the stems and leaves of Clausena emarginata were separated and purified by column chromatographies on silica gel,ODS,Sephadex LH-20,and PR-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis,as well as comparisons with the data reported in the literature. Sixteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. emarginata,which were identified as siamenol( 1),murrastanine A( 2),3-formyl-1,6-dimethoxycarbazole( 3),3-methoxymethylcarbazole( 4),3-methylcarbazole( 5),murrayafoline A( 6),3-formylcarbazole( 7),3-formyl-1-hydroxycarbazole( 8),3-formyl-6-methoxycarbazole( 9),murrayanine( 10),murrayacine( 11),girinimbine( 12),nordentatin( 13),chalepin( 14),8-hydroxy-6-methoxy-3-pentylisocoumarin( 15) and ethyl orsellinate( 16). Compounds 1-4,14-16 were isolated from C. emarginata for the first time. Among them,compounds 1,2,15 and 16 were isolated from the genus Clausena for the first time. All isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines: HL-60,SMMC-7721,A-549,MCF-7 and SW480 in vitro. Compounds 12 and 14 showed significant inhibitory effects against various human cancer cell lines with IC_(50) values comparable to those of doxorubicin.

A new monoterpenoid indole alkaloid, 10-methoxyakuammidine (1), together with four known alkaloids (2–5), were isolated from the stems and leaves of Ochrosia elliptica. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in the literature. New compound 1 was evaluated for its cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. 1 exhibited inhibitory effects with IC50 values comparable to those of cisplatin.

A series of novel 1,2,3-triazole-linked isosteviol derivatives were designed and synthesized via Huisgen-click reaction. Their cytotoxicities in vitro against HCT-116 and JEKO-1 cells were screened. The preliminary bioassays indicated that most of the title compounds exhibited noteworthy cytotoxic activities. Particularly, the compound 10b revealed the most potent inhibitory activities against HCT-116 cells with IC50 value of 2.987±0.098μM, which was better than that (3.906±0.261μM) of positive control cisplatin. On the basis of these bioactivity data, hologram quantitative structure-activity relationship (HQSAR) was performed, and a statistically reliable model with good predictive power (r2=0.848, q2=0.544 and R2pred=0.982) was achieved. Additionally, the contribution maps derived from the optimal model explained the individual atomic contributions to the activity for each molecule.

// Yan-Ping Liu 1, 2, 3, * , Hui-Fang Zhu 1, 2, 3, * , Ding-li Liu 4, * , Zhi-Yan Hu 1, 2, 3 , Sheng-Nan Li 1, 2, 3 , He-Ping Kan 5 , Xiao-Yan Wang 1, 2, 3 , Zu-Guo Li 1, 2, 3 1 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China 2 Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou, China 3 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China 4 State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China 5 Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Xiao-Yan Wang, email: wangxiaoyan639@163.com Zu-Guo Li, email: Lizg@smu.edu.cn Keywords: decoy receptor 3, colorectal cancer, TGF-β3/SMAD signaling, metastasis, epithelial-mesenchymal transition Received: May 30, 2016 Accepted: September 28, 2016 Published: October 13, 2016 ABSTRACT Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo . Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro , and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo . Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells.

A series of novel isosteviol derivatives bearing amino alcohol and thiourea fragments have been stereo-selectively synthesized and screened for their in vitro cytotoxic activities against three human cancer cell lines (HCT-116, HGC-27 and JEKO-1). The results demonstrated that these compounds exhibited prominent cytotoxicities. Especially, the compound Iw displayed the most potent anticancer activities against HCT-116 cell with IC50 value of 1.450 μM. On the basis of this bioassay results, these derivatives were further investigated by the hologram quantitative structure-activity relationship (HQSAR) technique. The optimal HQSAR model with q(2) = 0.663, r(2) = 0.895, SEE = 0.179 was generated using A/B/H/Ch as fragment distinction parameters and 4-7 as fragment size. This model was employed to predict the cytotoxic activities of test set compounds, and the predicted values were in good agreement with the experimental results. The contribution maps derived from the optimal model explained the individual atomic contribution to the total activity of single molecule.

Three new carbazole alkaloids, zanthoaustrones A–C (1–3), as well as nine known compounds 4–12, were isolated and characterized from the roots of Zanthoxylum austrosinense Huang (Rutaceae). Their chemical structures were elucidated on the basis of extensive and comprehensive spectroscopic methods, while the known alkaloids were identified by the comparison of their observed spectroscopic data including NMR data, MS data and optical rotation values with the data described in the literature. Furthermore, the antiproliferative activities as well as the anti-inflammatory effects of all isolated alkaloids in vitro were evaluated. All obtained alkaloids 1–12 displayed notable antiproliferative activities against diverse human cancer cell lines exhibiting IC50 values in range of 0.85 ± 0.06 to 29.56 ± 0.17 µM, which is equivalent to the positive control (cisplatin) showing IC50 values ranging from 1.58 ± 0.09 to 28.69 ± 0.21 µM. Moreover, compounds 1–12 exhibited pronounced inhibitory activities on nitric oxide (NO) production with IC50 values displaying IC50 values in range of 0.89 ± 0.05 to 9.62 ± 0.15 µM, which is comparable to the positive control (hydrocortisone) holding an IC50 value of 4.06 ± 0.11 µM. These findings indicate that the separation and characterization of these alkaloids displaying significant antiproliferative activities together with anti-inflammatory effects from the roots of Z. austrosinense could be meaningful to the research and development of new anti-cancer drugs as well as anti-inflammatory agents.

The phytochemical study on the stems of Clausena lenis resulted in the isolation of three new prenylated coumarins, clauselenins A–C (1–3), together with nine known prenylated coumarins (4–12). The chemical structures of new prenylated coumarins (1–3) were elucidated by means of comprehensive spectral analyses and the known compounds (4–12) were determined by means of comparing their experimental spectral data with those described data in the literatures. All isolated prenylated coumarins were assessed for their anti-inflammatory effects together with anti-HIV activities in vitro. Prenylated coumarins 1–12 displayed remarkable inhibitory effects against nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with the IC50 values which are comparable to hydrocortisone. Meanwhile, prenylated coumarins 1–12 exhibited considerable anti-HIV-1 reverse transcriptase (RT) activities possessing EC50 values in the range of 0.17–9.08 µM. These findings indicate that the isolation and identification of these prenylated coumarins with pronounced anti-inflammatory effects as well as anti-HIV activities separated from the stems of C. lenis could be of great significance to the development of new anti-inflammatory and anti-HIV agents and their potential applications in the pharmaceutical industry.

A phytochemical investigation on the stems of

A new monoterpenoid indole alkaloid, ochroborbone (1), along with five known alkaloids (2–6), were isolated from the stems and leaves of Ochrosia borbonica. Among them, ochroborbone (1) is a rare C17-nor monoterpenoid indole alkaloid, and the known compounds (2-6) were isolated from Ochrosia for the first time. These structures were established on the basis of extensive spectroscopic methods. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1 and 2 exhibited inhibitory effects with IC50 values comparable with those of cisplatin.

A new naturally occurring trinoreudesmane sesquiterpene, artahongkongol A (

Objective To analyze the effectiveness and safety of laparoscopic sleeve gastrectomy (LSG) in treating obesity and its co-morbidities.Methods The clinical data of obese patients undergoing LSG in Peking Union Medical College Hospital from August 2012 to August 2017 were retrospectively analyzed. Medium-term outcome measures included excess weight loss (%EWL),co-morbidity improvement,and complications.Results Seventy-five obese patients comprising 28 men[ body mass index(BMI):(47.3±7.5)kg/m

The purpose of this study was to investigate the expression profile of circular RNA (circRNA) in gastric cancer cells MGC-803, SGC-7901 and NCI-N87 with different degrees of differentiation and normal gastric epithelial cells GES-1. High throughput circRNA microarray technique was used to detect the differential expression of circRNA between three kinds of differentiated gastric cancer cells and normal gastric epithelial cells. The interaction of microRNAs (miRNAs) with circRNAs was predicted by bioinformatics software, and circRNA, which might have great significance in gastric cancer, was identified by literature search. The results showed that there were 79 up-regulated circRNAs and 229 down-regulated circRNAs in gastric cancer cells with different degrees of differentiation compared with those in normal gastric epithelial cells. Through bioinformatics software analysis and literature retrieval, it was found that hsa_circ_0001897 was related to the staging and metastasis of gastric cancer, while the miR-150-5p, which combined with it, was closely related to many kinds of digestive tract tumors, such as colon cancer, liver cancer, and cholangiocarcinoma. The miR-16-5p, which has binding sites with hsa_circ_0008106 and hsa_circ_0060456, has been confirmed to be involved in the development of gastric cancer. The above results suggest that hsa_circ_0001897, hsa_circ_0008106 and hsa_circ_0060456 may be closely related to the occurrence and development of gastric cancer by interacting with miRNA.

A phytochemical investigation on the stems and leaves of

A phytochemical investigation on the stems and leaves of

In a previous cross-sectional study, we identified a multidimensional urinary classifier (HF1), which was associated with left ventricular dysfunction. We investigated whether HF1 predicts cardiovascular end points over and beyond traditional risk factors. In 791 randomly recruited Flemish (mean age, 51.2 years; 50.6% women), we quantified HF1 by capillary electrophoresis coupled with mass spectrometry. In addition, we measured cardiovascular risk factors. HF1 averaged −0.97 U (range, −3.26 to 2.60). Over 6.1 years (median), 35 participants died and 63, 45, and 22 experienced fatal or nonfatal cardiovascular, cardiac, or coronary events, respectively. The incidence of fatal combined with nonfatal cardiovascular and cardiac end points, standardized for sex and age, increased across thirds of the HF1 distribution ( P ≤0.014), whereas trends for all-cause mortality and coronary events were nonsignificant ( P ≥0.10). The multivariable-adjusted hazard ratios (+1-SD) were 1.30 (95% confidence interval, 1.03–1.65; P =0.029) and 1.39 (1.06–1.84; P =0.018) for cardiovascular and cardiac events in relation to HF1. For systolic pressure, the corresponding estimates were 0.97 (0.74–1.28; P =0.85) and 0.93 (0.67–1.29; P =0.66), respectively. The HF1 upper thresholds optimized by maximizing Younden’s index were −0.50 and −0.36 U for cardiovascular and cardiac end points, respectively. Prognostic accuracy significantly ( P ≤0.006) improved by adding HF1 to Cox models already including the other baseline predictors. Sensitivity analyses, from which we excluded 71 participants with previous cardiovascular disease, were confirmatory. In conclusion, over a 6-year period, the urinary proteome, but not systolic pressure, predicted cardiovascular and cardiac disease.

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low- and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (P≤0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation. ispartof: Hypertension vol:66 issue:1 pages:85-92 ispartof: location:United States status: published

No previous population study assessed sublingual capillary density (CD) or perfused boundary region (PBR). Lower PBR indicates greater glycocalyx width. In 252 Han and 220 She Chinese and 254 Flemish people (mean age, 51.1 years; 54.7% women), representing random population samples, we measured total and perfused CD and PBR in the sublingual capillary bed, using oblique profiled epi-illumination, and cardiovascular risk factors. In multivariable analyses, we modeled ethnicity as random effect. Significance level was α≤0.05. Compared with Chinese, Flemish had lower total (577 versus 546 n°/mm 2 ) and perfused (338 versus 320 n°/mm 2 ) CD, but similar perfused-to-total CD ratio (mean, 0.59). Perfused-to-total CD ratio increased with age (effect size per 1–SD increase, +0.015 per year), body mass index (+0.008 per kg/m 2 ), total cholesterol (+0.012 per mmol/L), and Framingham risk score (+0.018 per point) with no ethnic differences in these associations. For age and Framingham risk score, associations with perfused-to-total CD ratio were driven by positive relationships with perfused CD, whereas associations with total CD were nonsignificant. Chinese when compared with Flemish had higher hematocrit (43.0 versus 41.1%), PBR (2010 versus 1876 nm), and pulse rate (72.6 versus 63.3 bpm). PBR standardized for hematocrit, perfused CD, and pulse rate decreased with body mass index (–26.7 nm/kg/m2), mean arterial pressure (–30.6 nm/mm Hg), and diastolic pressure (–28.5 nm/mm Hg) with no ethnic differences in these associations. In conclusion, a higher cardiovascular risk profile is associated with functional recruitment of capillaries with preserved glycocalyx that protects the endothelial lining.

The development of drug resistance has largely limited the clinical outcome of anti-cancer treatment. Recent work has highlighted the involvement of non-coding RNAs, microRNAs (miRNAs), in cancer development. The present study aimed to investigate the role of miR-21 in the development of drug resistance to paclitaxel in gastric cancer cells. Our study found that the expression of miR-21 upregulated in the paclitaxel resistant cell line SGC7901/paclitaxel compared to its parental line SGC7901. Moreover, over-expression of miR-21 significantly decreased antiproliferative effects and apoptosis induced by paclitaxel, while knockdown of miR-21 dramatically increased antiproliferative effects and apoptosis induction by paclitaxel. Moreover, our results demonstrated that miR-21 may modulate the sensitivity to PTX, at least in part, by regulating the expression of P-glycoprotein.

CDC73/Parafibromin is a critical component of the Paf1 complex (PAF1C), which is involved in transcriptional elongation and histone modifications. Mutations of the human CDC73/HRPT2 gene are associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome, an autosomal dominant disorder. CDC73/parafibromin was initially recognized as a tumor suppressor by inhibiting cell proliferation via repression of cyclin D1 and c-myc genes. In recent years, it has also shown oncogenic features by activating the canonical Wnt/β-catenin signal pathway. Here, through limited proteolysis analysis, we demonstrate that the evolutionarily conserved human CDC73 N-terminal 111 residues form a globularly folded domain (hCDC73-NTD). We have determined a crystal structure of hCDC73-NTD at 1.02 Å resolution, which reveals a novel protein fold. CDC73-NTD contains an extended hydrophobic groove on its surface that may be important for its function. Most pathogenic CDC73 missense mutations associated with the HPT-JT syndrome are located in the region encoding CDC73-NTD. Our crystal and biochemical data indicate that most CDC73 missense mutations disrupt the folding of the hydrophobic core of hCDC73-NTD, while others such as the K34Q mutant reduce its thermostability. Overall, our results provide a solid structural basis for understanding the structure and function of CDC73 and its association with the HPT-JT syndrome and other diseases.

Six new polyoxygenated seco-cyclohexenes, artahongkongenes A–F (1–6), together with six known analogues (7–12) were isolated from the stems and leaves of Artabotrys hongkongensis. Their structures were elucidated by extensive spectroscopic methods. All new compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. New seco-cyclohexenes 1–6 showed significant inhibitory effects against various human cancer cell lines with IC50 values ranging from 0.26 to 16.58 μM.

Five new carbazole alkaloids, clausehainanines A-E (1-5), together with seven known analogues (6-12) were isolated from the stems and leaves of C. hainanensis. Their structures were elucidated by extensive spectroscopic methods. Among them, compounds 1-5 were an unusual type of carbazole alkaloids, possessing diverse isopentenyl derivatives as substituents at C-2. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Alkaloids 1-12 showed significant antiproliferative effects against various human cancer cell lines with IC50 values ranging from 0.12 to 15.56 μM. These findings suggest that the discoveries of these carbazole alkaloids with significant cytotoxic activities isolated from C. hainanensis could be of great importance to the development of new anticancer agents.

A new furanocoumarin, clauhainanin A (1), together with seven known furanocoumarins (2-8), were isolated from the stems and leaves of Clausena hainanensis. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in the literature. All known compounds (2-8) were isolated from C. hainanensis for the first time. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1-8 exhibited significant inhibitory effects with IC50 values ranging from 1.36 to 18.96 μM.

The epidemiologic characteristics of 631 infant pertussis cases12 months, which accounted for 57.42% of the total cases, were analyzed by descriptive epidemiology in Tianjin, between 2010 and 2015. The incidence of infants was 104.66/100,000, which was 118 times higher than in other age groups (P0.001). The primary type of pertussis simultaneously presented in households was adult-to-infant (70.51%). The parents were identified as the source of infection in 80.18% of cases for infants. The positive rate of placental antibody transfer was 31.06% and 3.13% for 3-month-old infants. Infants presented the highest age-specific pertussis incidence. The most important reason was parents were the important sources of infection, and secondly the lower level of antibodies in neonates and the rapid waning of maternal antibody titer.