Non-coding RNAs: targets for Chinese herbal medicine in treating myocardial fibrosis.

Cardiovascular diseases have become the leading cause of death in urban and rural areas. Myocardial fibrosis is a common pathological manifestation at the adaptive and repair stage of cardiovascular diseases, easily predisposing to cardiac death. Non-coding RNAs (ncRNAs), RNA molecules with no coding potential, can regulate gene expression in the occurrence and development of myocardial fibrosis. Recent studies have suggested that Chinese herbal medicine can relieve myocardial fibrosis through targeting various ncRNAs, mainly including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Thus, ncRNAs are novel drug targets for Chinese herbal medicine. Herein, we summarized the current understanding of ncRNAs in the pathogenesis of myocardial fibrosis, and highlighted the contribution of ncRNAs to the therapeutic effect of Chinese herbal medicine on myocardial fibrosis. Further, we discussed the future directions regarding the potential applications of ncRNA-based drug screening platform to screen drugs for myocardial fibrosis.

Work-family conflict among primary health workers during the COVID-19 pandemic: Its mediating role in the relationship between workload and job burnout.

AIMS AND OBJECTIVES: This study explores the situation of workload, work-family conflict and job burnout among primary health workers in China in the context of COVID-19 and identifies the mediating effect of work-family conflict between workload and job burnout. BACKGROUND: Since the breakout of the COVID-19 pandemic, primary health workers have been working on the frontline of the epidemic and may experience increasing workload, work-family conflict and job burnout. It is important to focus on the issue of how to alleviate job burnout of primary health workers. DESIGN: A cross-sectional study (STROBE) was used. METHODS: Data were collected from 785 primary health workers in China. Multiple regression analysis was used to examine the mediating effect of work-family conflict between workload and job burnout. RESULTS: 18.7%, 10.4% and 39.5% of respondents had high job burnout in the dimensions of emotional exhaustion, depersonalization and personal accomplishment, respectively. 34.6% of the respondents had high or very high workload, and 12.8% of the respondents had high or very high work-family conflict. Results of multiple regression analysis indicated that work-family conflict mediated the relationship between workload and job burnout. Workload (ß = .163, CI = .207-.549) and work-family conflict (ß = .211, CI = .311-.640) positively influenced job burnout, and workload (ß = .428, CI = .375-.508) positively influenced work-family conflict. CONCLUSION: The study indicated that primary health workers experienced a high level of job burnout, especially in the personal accomplishment dimension. Furthermore, this study verified the mediating effect of work-family conflict between workload and job burnout. RELEVANCE TO CLINICAL PRACTICE: Some interventions for alleviating workload, work-family conflict and job burnout should be taken, including workplace assistance programmes, family-friendly policies and a well-integrated healthcare system. NO PATIENT OR PUBLIC CONTRIBUTION: This study does not involve patient or public contribution in any part. IMPACT STATEMENT: Nurses and other primary health workers are health gatekeepers of residents and play a vital role in the healthcare system. Due to the breakout of COVID-19, they have taken more work and are more vulnerable to work overload, work-family conflict and the consequent job burnout. Some interventions should be taken to effectively alleviate their job burnout and improve their health and performance.

Research on the dentification of Panax ginseng and Panax quinquefolium using catalysed hairpin assembly technology.

INTRODUCTION: Panax ginseng and Panax quinquefolium are traditional Chinese herb medicines and similar in morphology and some chemical components but differ in drug properties, so they cannot be mixed. However, the processed products of them are often sold in the form of slices, powder, and capsules, which are difficult to identify by traditional morphological methods. Furthermore, an accurate evaluation of P. ginseng, P. quinquefolium and the processed products have not been conducted. OBJECTIVE: This study aimed to establish a catalysed hairpin assembly (CHA) identification method for authenticating products made from P. ginseng and P. quinquefolium based on single nucleotide polymorphism (SNP) differences. METHOD: By analysing the differences of SNP in internal transcribed spacer 2 (ITS2) in P. ginseng and P. quinquefolium to design CHA-specific hairpins. Establish a sensitive and efficient CHA method that can identify P. ginseng and P. quinquefolium, use the sequencing technology to verify the accuracy of this method in identifying Panax products, and compare this method with high-resolution melting (HRM). RESULTS: The reaction conditions of CHA were as follows: the ratio of forward and reverse primers, 20:1; hairpin concentration, 5 ng/µL. Compared with capillary electrophoresis, this method had good specificity and the limit of detection was 0.5 ng/µL. The result of Panax product identification with CHA method were coincidence with that of the sequencing method; the positive rate of CHA reaction was 100%. CONCLUSION: This research presents an effective identification method for authenticating P. ginseng and P. quinquefolium products, which is helpful to improve the quality of Panax products.

Anti-atherosclerosis mechanisms associated with regulation of non-coding RNAs by active monomers of traditional Chinese medicine.

Atherosclerosis is the leading cause of numerous cardiovascular diseases with a high mortality rate. Non-coding RNAs (ncRNAs), RNA molecules that do not encode proteins in human genome transcripts, are known to play crucial roles in various physiological and pathological processes. Recently, researches on the regulation of atherosclerosis by ncRNAs, mainly including microRNAs, long non-coding RNAs, and circular RNAs, have gradually become a hot topic. Traditional Chinese medicine has been proved to be effective in treating cardiovascular diseases in China for a long time, and its active monomers have been found to target a variety of atherosclerosis-related ncRNAs. These active monomers of traditional Chinese medicine hold great potential as drugs for the treatment of atherosclerosis. Here, we summarized current advancement of the molecular pathways by which ncRNAs regulate atherosclerosis and mainly highlighted the mechanisms of traditional Chinese medicine monomers in regulating atherosclerosis through targeting ncRNAs.

Nitrate Radical Induced "Two in One" Interface Engineering toward High Reversibility of Zn Metal Anode.

Advanced interfacial engineering performs a forceful modulation effect on Zn2+ plating/stripping with simultaneous inhibition of hydrogen evolution reaction, chemical corrosion, and dendrite growth, which is responsible for high reversibility of Zn anode. Herein, a "two in one" interface engineering is developed to improve the reversibility of Zn anode, in which multi-functional Zn5 (NO3 )2 (OH)8 ·2H2 O layer and preferential Zn (002) texture are constructed simultaneously. Due to nucleophilicity to Zn2+ arising from electronegativity, the layer can accelerate the desolvation process of [Zn (H2 O)6 ]2+ and transfer kinetics of Zn2+ ions, leading to uniform nucleation and effective inhibition of water-induced side reactions. Meanwhile, the latter is beneficial to guiding   Zn (002)-preferred orientation deposition with compact structure. Consequently, the Zn electrodes with such complementary interface modulation exhibit prominent reversibility. With an area capacity of 1 mAh cm-2 at 1 mA cm-2 , the symmetric cell operates steadily for 4000 h. Highly reversible Zn anode is maintained even at 50 mA cm-2 . For full cells coupled with MnO2 cathode, impressive rate capability and cycling stability with a high capacity beyond 100 mAh g-1 at 1 A g-1 after 2000 cycles are achieved. The results provide new insights into Zn anodes with high reversibility for next-generation aqueous zinc ion batteries.

Development and application of a visualization method for identification of Panax species with LAMP and a DNAzyme.

Panax ginseng and Panax quinquefolium are two valuable Chinese herbal medicines that should not be mixed because they differ in drug properties and efficacy. The traditional identification method is easily affected by subjective factors and cannot effectively distinguish between ginseng products. This study aimed to develop a new chemical analysis method to visually identify P. ginseng and P. quinquefolium. In this method, a large number of sequences containing G-quadruplex were generated by loop-mediated isothermal amplification, and the combination of G-quadruplex and hemin was used to form deoxyribozyme, which catalyzed the color change of H2O2. Artificial simulation of adulteration experiments revealed that this method could detect more than 20% adulterated P. quinquefolium. Compared with the traditional identification methods, this technology was simpler and more efficient, providing a reference for developing rapid visual identification methods and reagents for P. ginseng and P. quinquefolium.

Case report: Curing a rare, unstable hemoglobin variant Hb Bristol-Alesha using haploidentical hematopoietic stem cell transplantation.

Unstable hemoglobinopathies are a rare, heterogeneous group of diseases that disrupt the stability of hemoglobin (Hb), leading to chronic hemolysis and anemia. Patients with severe phenotypes often require regular blood transfusions and iron chelation therapy. Although rare, studies have reported that hematopoietic stem cell transplantation (HSCT) seems to be an available curative approach in transfusion-dependent patients with unstable hemoglobinopathies. Here, we describe successful haploidentical HSCT for the treatment of an unstable Hb variant, Hb Bristol-Alesha, in a 6-year-old boy with severe anemia since early childhood. Two years after transplantation, he had a nearly normal hemoglobin level without evidence of hemolysis. DNA analysis showed complete chimerism of the donor cell origin, confirming full engraftment with normal erythropoiesis.

Identification of leaf chloroplast-specific promoter to efficiently control of Colorado potato beetle with reduced dsRNA accumulation in potato tubers.

BACKGROUND: By expressing double-stranded RNA (dsRNA) in potato plastids targeting the ß-Actin (ACT) gene of the Colorado potato beetle (CPB), transplastomic plants can trigger the beetle's RNA interference response to kill the CPB larvae. High expression of dsACT driven by rrn16 promoter (Prrn) in the leaf chloroplasts of transplastomic plants confers strong resistance to CPB. However, there are still residual amounts of dsRNA in the tubers, which are unnecessary for CPB control and may raise a potential food exposure issue. RESULTS: In order to reduce dsRNA accumulation in the tubers while maintaining stable resistance to CPB, we selected two promoters (PrbcL and PpsbD) from potato plastid-encoded rbcL and psbD genes and compared their activities with Prrn promoter for dsRNA synthesis in the leaf chloroplasts and tuber amyloplasts. We found that the dsACT accumulation levels in leaves of transplastomic plants St-PrbcL-ACT and St-PpsbD-ACT were significantly reduced when compared to St-Prrn-ACT, but they still maintained high resistance to CPB. By contrast, a few amounts of dsACT were still accumulated in the tubers of St-PrbcL-ACT, whereas no dsACT accumulation in tubers was detectable in St-PpsbD-ACT. CONCLUSION: We identified PpsbD as a useful promoter to reduce dsRNA accumulation in potato tubers while maintaining the high resistance of the potato leaves to CPB. © 2023 Society of Chemical Industry.

NIR-II Imaging-Guided Mitochondrial-Targeting Organic Nanoparticles for Multimodal Synergistic Tumor Therapy.

Effectively interfering energy metabolism in tumor cells and simultaneously activating the in vivo immune system to perform immune attacks are meaningful for tumor treatment. However, precisely targeted therapy is still a huge challenge. Herein, a mitochondrial-targeting phototheranostic system, FE-T nanoparticles (FE-T NPs) are developed to damage mitochondria in tumor cells and change the tumor immunosuppressive microenvironment. FE-T NPs are engineered by encapsulating the near-infrared (NIR) absorbed photosensitizer IR-FE-TPP within amphiphilic copolymer DSPE-SS-PEG-COOH for high-performing with simultaneous mitochondrial-targeting, near-infrared II (NIR-II) fluorescence imaging, and synchronous photothermal therapy (PTT) /photodynamic therapy (PDT) /immune therapy (IMT). In tumor treatment, the disulfide in the copolymer can be cleaved by excess intracellular glutathione (GSH) to release IR-FE-TPP and accumulate in mitochondria. After 808 nm irradiation, the mitochondrial localization of FE-T NPs generated reactive oxygen species (ROS), and hyperthermia, leading to mitochondrial dysfunction, photoinductive apoptosis, and immunogenic cell death (ICD). Notably, in situ enhanced PDT/PTT in vivo via mitochondrial-targeting with FE-T NPs boosts highly efficient ICD toward excellent antitumor immune response. FE-T NPs provide an effective mitochondrial-targeting phototheranostic nanoplatform for imaging-guided tumor therapy.

Intracellular Formation of Hemicyanine Nanoparticle Enhances Tumor-Targeting Photoacoustic Imaging and Photothermal Therapy.

Alkaline phosphatase (ALP) is a tumor marker for early diagnosis and treatment. Tumor targeting can recognize and fight tumor cells more accurately from healthy cells. Glycyrrhetinic acid (GA) is a targeting ligand of liver tumors. Photoacoustic imaging (PAI) and photothermal therapy (PTT) are promising techniques for tumor diagnosis and treatment. The outstanding characteristics of Hemicyanine (HCy) dye make it suitable for tumor diagnosis and treatment. However, using HCy nanoparticle (HCy NP) for liver tumor-targeting PAI and PTT has not been reported. Herein, Probe-1 is developed to enhance PAI and PTT of liver tumors due to GA targeting and intracellular ALP-instructed self-assembly of HCy NP. Compared to Probe-2 without self-assembly ability, Probe-1 displays a 4.6-fold higher PAI signal or 1.7-fold lower half inhibitory concentrations in HepG2 cells. Moreover, Probe-1 shows extended retention time (10 vs 6 h) and 2.1-fold higher PAI signal than Probe-2 in HepG2 tumors. The HepG2 tumors in Group Probe-1 obviously increase 18 °C (Tmax : 55 °C) with a 3.3-fold decreased volume while that in Group Probe-2 mildly increase 9.8 °C (Tmax : 46.8 °C) with a 4.3-fold increased volume. It is envisioned that this smart self-assembly strategy can be easily adjusted for PAI and PTT of more tumors.

A mitochondria-targeted molecular phototheranostic platform for NIR-II imaging-guided synergistic photothermal/photodynamic/immune therapy.

Phototherapy is a conducive and non-invasive strategy for cancer therapy under light irradiation. Inspiringly, fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds a great promise for imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. However, most phototherapeutics still face great challenges, including complicated synthesis of agents, potential biotoxicity and unsatisfied therapeutic outcomes. Herein, a near-infrared laser triggered molecular photosensitizer FEPT, modified with triphenylphosphine PEGylation (PEG2000-TPP), is developed for NIR-II imaging-guided mitochondria-targeting synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/immune therapy (IMT). The mitochondria-targeting photosensitizer FEPT can produce reactive oxygen species (ROS) and hyperpyrexia upon 808 nm laser irradiation, resulting in mitochondrial dysfunction and photo-induced apoptosis via caspase-3 pathway. Phototherapy-induced hyperthermia or ROS triggers the release of immunogenic intracellular substrates from dying tumor cells, thereby promoting the activation of antitumor immunity. Herein, this work provides a practicable strategy to develop a molecular phototheranostic platform for imaging-guided cancer therapy via mitochondria-targeting.

An esterase-activatable curcumin prodrug for tumor-targeting therapy.

A tumor-targeting therapy strategy is urgently needed to increase the accumulation of drugs in tumors and reduce the side effects in normal tissues. Herein, we developed an esterase-activatable curcumin prodrug Cur-RGD for tumor-targeting therapy. Armed with the tumor-targeting RGD peptide and in situ esterase-triggered drug release, this prodrug Cur-RGD can efficiently improve the therapeutic effect of curcumin in tumors.

Performance and mechanism of simultaneous nitrification-denitrification and denitrifying phosphorus removal in long-term moving bed biofilm reactor (MBBR).

The long-term moving bed biofilm reactor (MBBR) with carrier-attached biofilm was successfully operated for simultaneous removal of nitrogen, phosphorus, and COD at various C/N ratios. Results indicated that 99.60%, 63.58%, 78.94%, and 59.64% of NH4+-N, NO3--N, TN, and TP were removed at C/N ratio, hydraulic retention time (HRT), and carrier film amount of 5, 40 h, and 1.2 mg·g-1. Nitrogen balance analysis showed that more than 89% of nitrogen (C/N = 20, 15, 10, 5) was converted to gas products. Extracellular polymeric substances (EPS), electron transport system activity (ETSA), and enzyme activity of biofilm were evaluated. Protein (PN)/polysaccharose (PS) values and ETSA decreased with the decrease of C/N ratios. Metagenomics sequencing further revealed that the prominent phyla for nitrogen and phosphorus removal were identified including Proteobacteria, Acidobacteria, Nitrospirae, and Chloroflexi. Proteobacteriaand Gammaproteobacteria were identified as the dominant denitrifying phosphate accumulating organisms (PAO) at the phylum and class level, respectively.

Chrysanthemi Flos extract alleviated acetaminophen-induced rat liver injury via inhibiting oxidative stress and apoptosis based on network pharmacology analysis.

CONTEXT: Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury. Bianliang ziyu, a variety of Chrysanthemum morifolium Ramat. (Asteraceae), has potential hepatoprotective effect. However, the mechanism is not clear yet. OBJECTIVE: To investigate the hepatoprotective activity and mechanism of Bianliang ziyu flower ethanol extract (BZE) on APAP-induced rats based on network pharmacology. MATERIALS AND METHODS: Potential pathways of BZE were predicted by network pharmacology. Male Sprague-Dawley rats were pre-treated with BZE (110, 220 and 440 mg/kg, i.g.) for eight days, and then APAP (800 mg/kg, i.g.) was used to induce liver injury. After 24 h, serum and liver were collected for biochemical detection and western blot measurement. RESULTS: Network pharmacology indicated that liver-protective effect of BZE was associated with its antioxidant and anti-apoptotic efficacy. APAP-induced liver pathological change was alleviated, and elevated serum AST and ALT were reduced by BZE (440 mg/kg) (from 66.45 to 22.64 U/L and from 59.59 to 17.49 U/L, respectively). BZE (440 mg/kg) reduced the ROS to 65.50%, and upregulated SOD and GSH by 212.92% and 175.38%, respectively. In addition, BZE (440 mg/kg) increased levels of p-AMPK, p-GSK3ß, HO-1 and NQO1, ranging from 1.66- to 10.29-fold compared to APAP group, and promoted nuclear translocation of Nrf2. BZE also inhibited apoptosis induced by APAP through the PI3K-Akt pathway and restored the ability of mitochondrial biogenesis. DISCUSSION AND CONCLUSIONS: Our study demonstrated that BZE protected rats from APAP-induced liver injury through antioxidant and anti-apoptotic pathways, suggesting BZE could be further developed as a potential liver-protecting agent.

Cinnamic Acid Ameliorates Nonalcoholic Fatty Liver Disease by Suppressing Hepatic Lipogenesis and Promoting Fatty Acid Oxidation.

BACKGROUND: Cinnamic acid (CA) has been shown to have many beneficial effects including regulating lipid metabolism and reducing obesity. However, its effect on nonalcoholic fatty liver disease (NAFDL) has not been investigated in detail. Thus, we performed this study in order to explore CA's effect on hepatic lipid metabolism and the underlying mechanisms. METHOD: Oleic acid (OA) was used to induce lipid accumulation in HepG2 cells. After coincubation with CA, the cells were stained with oil red O and the triglyceride (TG) content was assessed. Key genes in lipogenesis and fatty acid oxidation pathways were tested. Additionally, db/db and wt/wt mice were divided into three groups, with the wt/wt mice representing the normal group and the db/db mice being divided into the NAFLD and CA groups. After 4 weeks of oral treatment, all mice were sacrificed and the blood lipid profile and liver tissues were assessed. RESULTS: CA treatment reduced the lipid accumulation in HepG2 cells and in db/db mouse livers. ACLY, ACC, FAS, SCD1, PPARγ, and CD36 were significantly downregulated, while CPT1A, PGC1α, and PPARα were significantly upregulated. CONCLUSION: CA's therapeutic effect on NAFLD may be attributed to its ability to lower hepatic lipid accumulation, which is mediated by suppression of hepatic lipogenesis and fatty acid intake, as well as increased fatty acid oxidation.

Comparison of physical electrical conductivity and acupuncture de-qi sensation between stainless steel needling and supercritical fluid-treated needling.

BACKGROUND: While acupuncture has been used for thousands of years, modern technology to develop new needle materials has rarely been discussed. We aim to explore a new acupuncture needle material and compare the differences in the needling sensations between the acupuncture needle surface treated with nitrogen applied supercritical fluid (SCF-N) and conventional stainless steel needles. METHODS: This was a double-blind cohort study. The acupuncture needles were randomly used in this experiment, including the SCF-N-treated needles and the control stainless steel needles. LI 4 (Hegu) and LI 11 (Quchi) acupuncture points in the Yangming Large Intestine Meridian of Hand were treated. Physical electrical resistance, scanning electron microscopy, energy dispersive spectrometry, and visual analog scale (VAS) score including the sensations of soreness, numbness, distention, and heaviness were assessed. RESULTS: The proportion of nitrogen (N) was significantly higher in the SCF-N-treated needles than in the stainless steel needles group (2.3 ± 0.2% vs 0.0 ± 0.0%, P < 0.01). The cumulative de-qi sensation score at the LI 4 Hegu acupoint (1.87 ± 1.88 vs 1.54 ± 1.62, P = 0.014), especially the sensation of soreness score (2.76 ± 2.06 vs 2.13 ± 1.85, P = 0.045), revealed statistically significant differences between both groups. SCF-N surface treatment of acupuncture needles may lower the electrical resistance more than the control stainless steel needles (24.67 ± 0.88 kW vs 26.45 ± 0.75 kW, p < 0.01). CONCLUSION: Acupuncture needles modified with SCF-N surface treatment can enhance de-qi sensations to improve electrical conductivity of the meridian and therapeutic effects on the Yangming Large Intestine Meridian of Hand. SCF-N surface treated needles can be as a new acupuncture needle material in the future.

The Activity of Small Urea-γ-AApeptides Toward Gram-Positive Bacteria.

Host Defense Peptides (HDPs) have gained considerable interest due to the omnipresent threat of bacterial infection as a serious public health concern. However, development of HDPs is impeded by several drawbacks, such as poor selectivity, susceptibility to proteolytic degradation, low-to-moderate activity and requiring complex syntheses. Herein we report a class of lipo-linear α/urea-γ-AApeptides with a hybrid backbone and low molecular weight. The heterogeneous backbone not only enhances chemodiversity, but also shows effective antimicrobial activity against Gram-positive bacteria and is capable of disrupting bacterial membranes and killing bacteria rapidly. Given their low molecular weight and ease of access via facile synthesis, they could be practical antibiotic agents.

Tumour-specific amplitude-modulated radiofrequency electromagnetic fields induce differentiation of hepatocellular carcinoma via targeting Cav3.2 T-type voltage-gated calcium channels and Ca2+ influx.

BACKGROUND: Administration of amplitude modulated 27·12 MHz radiofrequency electromagnetic fields (AM RF EMF) by means of a spoon-shaped applicator placed on the patient's tongue is a newly approved treatment for advanced hepatocellular carcinoma (HCC). The mechanism of action of tumour-specific AM RF EMF is largely unknown. METHODS: Whole body and organ-specific human dosimetry analyses were performed. Mice carrying human HCC xenografts were exposed to AM RF EMF using a small animal AM RF EMF exposure system replicating human dosimetry and exposure time. We performed histological analysis of tumours following exposure to AM RF EMF. Using an agnostic genomic approach, we characterized the mechanism of action of AM RF EMF. FINDINGS: Intrabuccal administration results in systemic delivery of athermal AM RF EMF from head to toe at levels lower than those generated by cell phones held close to the body. Tumour shrinkage results from differentiation of HCC cells into quiescent cells with spindle morphology. AM RF EMF targeted antiproliferative effects and cancer stem cell inhibiting effects are mediated by Ca2+ influx through Cav3·2 T-type voltage-gated calcium channels (CACNA1H) resulting in increased intracellular calcium concentration within HCC cells only. INTERPRETATION: Intrabuccally-administered AM RF EMF is a systemic therapy that selectively block the growth of HCC cells. AM RF EMF pronounced inhibitory effects on cancer stem cells may explain the exceptionally long responses observed in several patients with advanced HCC. FUND: Research reported in this publication was supported by the National Cancer Institute's Cancer Centre Support Grant award number P30CA012197 issued to the Wake Forest Baptist Comprehensive Cancer Centre (BP) and by funds from the Charles L. Spurr Professorship Fund (BP). DWG is supported by R01 AA016852 and P50 AA026117.

Diachronic changes in craniofacial morphology among the middle-late Holocene populations from Hehuang region, Northwest China.

OBJECTIVES: This study analyzes craniofacial shape variation in the Hehuang region of Northwest China within a population genetic framework, and takes a diachronic approach to explore the relationship betwee cultural discontinuity and biological continuity/discontinuity in the Hehuang region during the middle to late Holocene. MATERIALS AND METHODS: The sample comprises 76 adult skulls from five archaeological sites, ranging from 4,500 to 1,530 BP. 3D geometric morphometrics, multivariate statistics, quantitative evolutionary genetic and biodistance analyses were performed to study the diachronic variation in craniofacial morphology. Analyses were performed on two cranial modules: the face and the cranial vault, across three major diachronic groups representing the late Neolithic (LNA), the Bronze Age (BA), and the Han-Jin dynasty (HD). RESULTS: Average regional FST for both cranial modules was low, indicating relatively greater variation within diachronic groups than among them. While the LNA and BA groups did not show any significant differences in facial and vault shape, significant craniofacial shape changes were detected between the BA and HD groups. DISCUSSION: The consistent craniofacial morphology during the LNA and the BA, and the shift in morphology between the BA and the HD indicates that cultural discontinuity does not always coincide with biological discontinuity. The Hehuang population evolved in situ with few changes, despite cultural and dietary changes, until the HD when migrations from the Central Plains are associated with extra-local gene flow to the area.

Genomic Signature of Driver Genes Identified by Target Next-Generation Sequencing in Chinese Non-Small Cell Lung Cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most common human malignancies and the leading cause of cancer-related death. Over the past few decades, genomic alterations of cancer driver genes have been identified in NSCLC, and molecular testing and targeted therapies have become standard care for lung cancer patients. Here we studied the unique genomic profile of driver genes in Chinese patients with NSCLC by next-generation sequencing (NGS) assay. MATERIALS AND METHODS: A total of 1,200 Chinese patients with NSCLC were enrolled in this study. The median age was 60 years (range: 26-89), and 83% cases were adenocarcinoma. NGS-based genomic profiling of major lung cancer-related genes was performed on formalin-fixed paraffin-embedded tumor samples and matched blood. RESULTS: Approximately 73.9% of patients with NSCLC harbored at least one actionable alteration recommended by the National Comprehensive Cancer Network guideline, including epidermal growth factor receptor (EGFR), ALK, ERBB2, MET, BRAF, RET, and ROS1. Twenty-seven patients (2.2%) harbored inherited germline mutations of cancer susceptibility genes. The frequencies of EGFR genomic alterations (both mutations and amplification) and ALK rearrangement were identified as 50.1% and 7.8% in Chinese NSCLC populations, respectively, and significantly higher than the Western population. Fifty-six distinct uncommon EGFR mutations other than L858R, exon19del, exon20ins, or T790M were identified in 18.9% of patients with EGFR-mutant NSCLC. About 7.4% of patients harbored both sensitizing and uncommon mutations, and 11.6% of patients harbored only uncommon EGFR mutations. The uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. In patients <40 years of age, the ALK-positive percentage was up to 28.2%. Moreover, 3.2% of ALK-positive patients harbored multi ALK rearrangements, and seven new partner genes were identified. CONCLUSION: More unique features of cancer driver genes in Chinese NSCLC were identified by next-generation sequencing. These findings highlighted that NGS technology is more feasible and necessary than other molecular testing methods, and suggested that the special strategies are needed for drug development and targeted therapy for Chinese patients with NSCLC. IMPLICATIONS FOR PRACTICE: Molecular targeted therapy is now the standard first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). Samples of 1,200 Chinese patients with NSCLC were analyzed through next-generation sequencing to characterize the unique feature of uncommon EGFR mutations and ALK fusion. The results showed that 7.4% of EGFR-mutant patients harbored both sensitizing and uncommon mutations and 11.6% harbored only uncommon mutations. Uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. ALK fusion was more common in younger patients, and the frequency decreased monotonically with age. 3.2% of ALK-positive patients harbored multi ALK rearrangement, and seven new partner genes were identified.