The purpose of this study was to enrich the genomic information and provide a basis for further development and utilization of Polygonatum kingianum. The fresh rhizome of P. kingianum was used as the experimental material, and the full-length transcriptome was sequenced by PacBio Sequel platform. The final measured polymerase reads were 1 120 485, with a total of 77.73 GB of data. In NR database, 41 864 homologous sequence alignments were aligned to 5 species; 40 506 were annotated in the KOG database and classified into 26 categories based on their functionality; 69 060 GO annotated 32 functional groups divided into 3 categories: cellular components, molecular functions, and biological processes; 45 779 annotations were added to 145 metabolic pathways in the KEGG database. Among them, there are 127 identified transcripts related to polysaccharide synthesis in the glycolysis/gluconeogenesis metabolic pathway, 144 in the starch and sucrose metabolic pathway, 85 in the amino acid sugar and nucleotide sugar metabolic pathway, and 69 in the fructose and mannose metabolic pathway. In addition, 1 781 transcription factors were detected, distributed in 37 transcription factor families; 180 293 SSR loci were detected, among which single base repeats accounted for the most, accounting for 30.48% of all base repeats, and at least five base repeats, accounting for only 0.14% of single base repeats. The results of this study provide important data supporting for enriching the genomic information of P. kingianum and exploring its effective biosynthetic pathway.

Objective To investigate the correlation between tongue and pulse indicators and the out-come of live birth in patients undergoing frozen-thawed embryo transfer(FET),as well as the association between these indicators and patients'endocrine parameters. Methods This study was conducted at Reproductive Medicine Center,Shuguang Hospital Af-filiated to Shanghai University of Traditional Chinese Medicine,Shanghai,China,from March 8,2021 to January 5,2022.Patients undergoing FET were divided into live birth and non-live birth groups according to their live birth outcome.The differences between the endocrine pa-rameters[basic follicle stimulating hormone(b FSH),basic luteinizing hormone(b LH),basic estradiol(b E2),basic progesterone(b P),basal endometrial thickness,follicle stimulating hormone(FSH)on endometrial transition day,luteinizing hormone(LH)on endometrial transition day,estradiol(E2)on endometrial transition day,progesterone(P)on endometrial transition day,and endometrial thickness on endometrial transition day]and the tongue and pulse indicators[tongue body(TB)-L,TB-a,TB-b,tongue coating(TC)-L,TC-a,TC-b,perAll,perPart,h1,h4,h5,t1,h1/t1,and h4/h1]of patients in the two groups were analyzed,with the correlation between these variables analyzed as well using Spearman's correlation coefficient.Multivariate logistic regression was employed to identify the influential factors in the live birth prediction models across various datasets,including Model 1 consisting of endocrine indica-tors only,Model 2 solely consisting of tongue and pulse indicators,and Model 3 consisting of both tongue,pulse,and endocrine indicators,as well as to evaluate efficacy of the models de-rived from different datasets. Results This study included 78 patients in live birth group and 144 patients in non-live birth group.Compared with non-live birth group,live birth group exhibited higher levels of TB-L(P=0.01)and TB-a(P=0.04),while demonstrated lower levels of b FSH(P=0.01),perAll(P=0.04),and h4/h1(P=0.03).The Spearman's correlation coefficient analysis revealed statisti-cally significant correlation(P<0.05)between TB-L,TB-b,TC-L,TC-b,perAll,perPart,h4,h5,t1,h1/t1 and b FSH,b LH,basal endometrial thickness,LH on endometrial transition day,E2 on endometrial transition day,P on endometrial transition day,and endometrial thickness on endometrial transition day in live birth group.The multivariate logistic regression analysis showed that the prediction Model 3 for live birth outcome[area under the curve(AUC):0.917,95%confidence interval(CI):0.863-0.971,P<0.001]surpassed the Model 1(AUC:0.698,95%CI:0.593-0.803,P=0.001),or the Model 2(AUC:0.790,95%CI:0.699-0.880,P<0.001).The regression equations for the live birth outcomes,integrating tongue and pulse indicators with endocrine parameters,included the following measures:FSH on endometrial transition day[odds ratio(OR):0.523,P=0.025],LH on endometrial transition day(OR:1.277,P=0.029),TB-L(OR:2.401,P=0.001),perPart(OR:1.018,P=0.013),h1(OR:0.065,P=0.021),t1(OR:4.354,P=0.024),and h4/h1(OR:0.018,P=0.016). Conclusion In infertility patients undergoing FET,there exists a correlation between tongue and pulse indicators and endocrine parameters.The corporation of tongue and pulse indica-tors significantly improved the predictive capability of the model for live birth outcomes.Specifically,tongue and pulse indicators such as TB-L,perPart,h1,t1,and h4/h1 exhibited a discernible correlation with the ultimate live birth outcomes.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective To investigate the clinical efficacy of triamcinolone acetonide combined with punch excision in the treatment of keloids.Methods Patients with keloids diagnosed and treated in The First Affiliated Hospital,Zhejiang University School of Medicine from January 2021 to January 2022 were retrospectively collected.Patients with keloids were divided into conservative(triamcinolone acetonide and fluorouracil)and non-conservative(punch excision combined with treamcinolone acetonide and fluorouracil)according to their treatment regimens.The scores of the Patient and Observer Scar Assessment Scale(POSAS),the Vancouver Scar Scale(VSS)and the Visual Analogue Rating Scale(VAS)were compared before and after treatment,the total effective rate was calculated to evaluate,the clinical efficacy,and the occurrence of adverse events was observed to evaluate the safety.Results A total of 99 patients with keloids were included in the study,including 53 in the conservative treatment group and 46 in the non-conservative treatment group.Before treatment,there was no significant difference in POSAS score,VSS score and VAS score between the two groups(P>0.05).Compared with the conservative treatment group,the POSAS score,VSS score and VAS score of the non-conservative treatment group decreased significantly after treatment(P<0.05).The total effective rate of treatment in the non-conservative treatment group was significantly higher than that in the conservative treatment group(P<0.05).In terms of adverse reactions,the risk of bleeding increased,the incidence of skin pigmentation decreased,and the telangiecasia and skin atrophy didn't occur in the non-conservative treatment group.Conclusion Triamcinolone acetonide combined with punch excision has a significant effect on keloids,which can reduce the incidence of skin atrophy but increase the risk of bleeding.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Objective:To investigate the expression of long non-coding RNA 00665 (LINC00665) in hepatocellular carcinoma (HCC) and its regulatory effect on angiogenesis of hepatocellular carcinoma cells and its potential molecular mechanism.Methods:HCC tissues and corresponding paracancerous tissues of 100 patients with HCC in the First Affiliated Hospital of Nanjing Medical University from May 2016 to April 2017 were collected, and the survival prognosis was compared. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of LINC00665 in HCC tissues and cells. The effect of LINC00665 overexpressed Hep-3B cells on the angiogenesis of human umbilical vein endothelial cells (HUVEC) was examined by tube formation assay and chick chorioallantoic membrane assay. Bioinformatics database predicted the downstream microRNA (miRNA) and target genes of LINC00665, and the relationship between LINC00665, miR-126-5p and vascular endothelial growth factor A (VEGFA) was verified by RT-qPCR, Western blot and dual-luciferase reporter gene assay.Results:The expression level of LINC00665 in HCC (6.5±2.8) was significantly higher than that in paracancer tissues (4.8±3.1), the difference was statistically significant ( t=4.12, P<0.001). According to the median LINC00665 expression level of 100 patients with HCC, the cumulative survival rate of LINC00665 high expression group ( n=50) was lower than that of LINC00665 low expression group ( n=50), and the difference was statistically significant (χ 2=3.79, P=0.008). After co-culture with LINC00665 group (Hep-3B cells overexpressing LINC00665), the length of HUVEC cell tubule formation was (596.0±22.3) μm, and the number of HUVEC cell tubules was (36.3±4.5), which were both higher than NC group with the tubule formation length (127.0±13.5) μm and the number (9.3±1.5) of HUVEC cells co-cultured with Hep-3B cells of control group, and the differences were statistically significant ( t=31.15, 9.82, P<0.001, P=0.001). The chick chorioallantoic membrane assay results were similar to tube formation assay. Western blot detected that the relative expression of VEGFA in LINC00665 group was higher than that in NC group, the difference was statistically significant ( t=7.15, P<0.001). StarBase and DIANA database were used to predict and screen LINC00665 downstream miR-126-5p. StarBase database was used to predict the binding sites of LINC00665/miR-126-5p/VEGFA axis. In dual-luciferase reporter gene assay, the fluorescence intensity of LINC00665 and VEGFA vector co-transfected with miR-126-5p mimics decreased. Conclusion:LINC00665 is highly expressed in HCC and is associated with poor prognosis in patients with HCC. LINC00665 promotes angiogenesis of HCC by regulating the miR-126-5p/VEGFA axis.

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

This study investigated the mechanism of Gegen Qinlian Decoction(GQD) in improving glucose metabolism in vitro and in vivo by alleviating endoplasmic reticulum stress(ERS). Molecular docking was used to predict the binding affinity between the main effective plasma components of GQD and ERS-related targets. Liver tissue samples were obtained from normal rats, high-fat-induced diabetic rats, rats treated with metformin, and rats treated with GQD. RNA and protein were extracted. qPCR was used to measure the mRNA expression of ERS marker glucose-regulated protein 78(GRP78), and unfolded protein response(UPR) genes inositol requiring enzyme 1(Ire1), activating transcription factor 6(Atf6), Atf4, C/EBP-homologous protein(Chop), and caspase-12. Western blot was used to detect the protein expression of GRP78, IRE1, protein kinase R-like ER kinase(PERK), ATF6, X-box binding protein 1(XBP1), ATF4, CHOP, caspase-12, caspase-9, and caspase-3. The calcium ion content in liver tissues was determined by the colorimetric assay. The ERS-HepG2 cell model was established in vitro by inducing with tunicamycin for 6 hours, and 2.5%, 5%, and 10% GQD-containing serum were administered for 9 hours. The glucose oxidase method was used to measure extracellular glucose levels, flow cytometry to detect cell apoptosis, glycogen staining to measure cellular glycogen content, and immunofluorescence to detect the expression of GRP78. The intracellular calcium ion content was measured by the colorimetric assay. Whereas Western blot was used to detect GRP78 and ERS-induced IRE1, PERK, ATF6, and eukaryotic translation initiation factor 2α(eIF2α) phosphorylation. Additionally, the phosphorylation levels of insulin receptor substrate 1(IRS1), phosphatidylinositol 3-kinase regulatory subunit p85(PI3Kp85), and protein kinase B(Akt), which were involved in the insulin signaling pathway, were also measured. In addition, the phosphorylation levels of c-Jun N-terminal kinases(JNKs), which were involved in both the ERS and insulin signaling pathways, were measured by Western blot. Molecular docking results showed that GRP78, IRE1, PERK, ATF4, and various compounds such as baicalein, berberine, daidzein, jateorhizine, liquiritin, palmatine, puerarin and wogonoside had strong binding affinities, indicating that GQD might interfere with ERS-induced UPR. In vivo results showed that GQD down-regulated the mRNA transcription of Ire1, Atf6, Atf4, Grp78, caspase-12, and Chop in diabetic rats, and down-regulated GRP78, IRE1, PERK, as well as ERS-induced apoptotic factors ATF4 and CHOP, caspase-12, caspase-9, and caspase-3, while up-regulating XBP1 to enhance adaptive UPR. In addition, GQD increased the calcium ion content in liver tissues, which facilitated correct protein folding. In vitro results showed that GQD increased glucose consumption in ERS-induced HepG2 cells without significantly affecting cell viability, increased liver glycogen synthesis, down-regulated ATF6 and p-eIF2α(Ser51), and down-regulated IRE1, PERK, and GRP78, as well as p-IRS1(Ser312) and p-JNKs(Thr183/Tyr185), while up-regulating p-PI3Kp85(Tyr607) and p-Akt(Ser473). These findings suggested that GQD alleviates excessive ERS in the liver, reduces insulin resistance, and improves hepatic glucose metabolism in vivo and in vitro.
Rats ; Animals ; Proto-Oncogene Proteins c-akt ; Endoplasmic Reticulum Chaperone BiP ; Caspase 3 ; Caspase 9 ; Diabetes Mellitus, Experimental ; Caspase 12 ; Calcium/pharmacology* ; Molecular Docking Simulation ; Endoplasmic Reticulum Stress ; Protein Serine-Threonine Kinases/genetics* ; Liver ; Apoptosis ; Insulin ; Glucose ; Glycogen/pharmacology* ; RNA, Messenger

OBJECTIVE: Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN. METHODS: Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4^-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN. RESULTS: The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4^-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure. CONCLUSION TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.
Animals ; Mice ; TRPV Cation Channels/metabolism* ; Intermediate Filaments/metabolism* ; Hippocampus/metabolism* ; Neurons/metabolism* ; Memory Disorders/metabolism*