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Abstract Chloroplast (cp) genome sequences have been extensively used for phylogenetic and evolutionary analyses, as many have been sequenced in recent years. Identification of Quercus is challenging because many species overlap phenotypically owing to interspecific hybridization, introgression, and incomplete lineage sorting. Therefore, we wanted to gain a better understanding of this genus at the level of the maternally inherited chloroplast genome. Here, we sequenced, assembled, and annotated the cp genomes of the threatened Quercus marlipoensis (160,995 bp) and Q. kingiana (161,167 bp), and mined these genomes for repeat sequences and codon usage bias. Comparative genomic analyses, phylogenomics, and selection pressure analysis were also performed in these two threatened species along with other species of Quercus. We found that the guanine and cytosine content of the two cp genomes were similar. All 131 annotated genes, including 86 protein-coding genes, 37 transfer RNA genes, and 8 ribosomal RNA genes, had the same order in the two species. A strong A/T bias was detected in the base composition of simple sequence repeats. Among the 59 synonymous codons, the codon usage pattern of the cp genomes in these two species was more inclined toward the A/U ending. Comparative genomic analyses indicated that the cp genomes of Quercus section Ilex are highly conserved. We detected eight highly variable regions that could be used as molecular markers for species identification. The cp genome structure was consistent and different within and among the sections of Quercus. The phylogenetic analysis showed that section Ilex was not monophyletic and was divided into two groups, which were respectively nested with section Cerris and section Cyclobalanopsis. The two threatened species sequenced in this study were grouped into the section Cyclobalanopsis. In conclusion, the analyses of cp genomes of Q. marlipoensis and Q. kingiana promote further study of the taxonomy, phylogeny and evolution of these two threatened species and Quercus.

Mycoplasma pneumoniae pneumonia （MPP） is a common cause of community-acquired pneumonia in children aged 5 and older in China. Although most affected children have favorable clinical prognosis， some cases can escalate into severe MPP due to risk factors such as pathogen resistance or co-infections， etc. These severe cases significantly jeopardize the lives of children and may lead to diverse long-term sequelae. In response to this challenge， the Children’s Medical Center of the Third Affiliated Hospital of Sun Yat-sen University， integrating current guidelines， expert consensus， and its extensive clinical experience， has devised the “412” cluster treatment strategy. This comprehensive approach encompasses treatments for anti-infection， anti-inflammatory storm， anticoagulation and antioxidant stress. Additionally， it seamlessly integrates traditional Chinese medicine with western therapies， featuring bundled respiratory management and follow-up care. This strategy provides a valuable reference for the diagnosis and treatment of severe MPP in children.

Background Against the backdrop of global aging, the number of patients with chronic diseases is increasing, and the multimorbidity is becoming more severe. Traditionally, cardiovascular diseases and type 2 diabetes are mostly considered diseases of the elderly. However, with changes in lifestyle patterns such as the pace of life and diet, many diseases are showing a trend of rejuvenation. Recent studies have also shown that individuals who develop diabetes at a young age have an increased relative risk of developing cardiovascular diseases and higher mortality rates compared to the general population. Objective To investigate the burden of cardiovascular diseases attributed to diabetes among Chinese adults from 1990 to 2019, so as to provide evidence for comorbidity prevention. Methods Based on the 2019 Global Burden of Disease (GBD) study data, indicators such as mortality rates, disability-adjusted life years (DALY) rates, and estimated annual percentage change (EAPC) were used to assess the burden of cardiovascular diseases in China (including ischemic heart disease, stroke, and peripheral arterial disease) attributed to diabetes. The analysis was stratified by age group (25-49 years, 50-69 years, ≥70 years) and gender, and the temporal trends in disease burden were finally analyzed. Results The number of cardiovascular disease deaths attributable to diabetes increased from 298 050 in 1990 to 700 340 in 2019 among people aged 25 years and older in China. The age-standardized mortality rate for CVD attributed to diabetes increased for males compared to 1990, while it decreased for females, with males consistently having higher rates than females. In 2019, the DALY for CVD attributed to diabetes was 13 585 850 person-years. The age-specific mortality rate and DALY rate increased with age. The downward trend in standardized DALY rate was more pronounced in females (EAPC=-0.32%, 95%CI=-0.49% to -0.11%) than in males (EAPC=-0.01%, 95%CI=-0.26% to 0.29%). The mortality and DALY rates for ischemic heart disease and peripheral arterial disease attributed to diabetes increased in the three age groups from 1990 to 2019, while the mortality rates for stroke attributed to diabetes declined in all three age groups in 2019 compared to 1990. The percentage of standardized DALY rates attributable to diabetes for the 3 cardiovascular diseases in cardiovascular disease fluctuated from 1990 to 2019. However, the percentage of standardized DALY rates for all 3 cardiovascular diseases attributable to diabetes was higher in 2019 than in 1990. Conclusion From 1990 to 2019, there has been an overall increasing trend in the mortality and DALY rates of cardiovascular diseases attributed to diabetes among adults in China. Population is at greater risk for comorbidities of diabetes and CVD, emphasizing the need to focus on screening for CVD among individuals with diabetes or those at high risk of developing CVD. Emphasis should be placed on males, the elderly, and younger individuals with unhealthy lifestyle habits for early health interventions to reduce the burden of comorbidities.

Background Lipid metabolism of middle-aged and older adults may be influenced by their late bedtime behavior, but the association between the above two still needs to be analyzed in-depth. Objective To explore the association between chronotype and dyslipidemia among populations with different gender, central obesity, late evening snacks and smoking. Methods A questionnaire survey was conducted among the population aged 40-65 years who received health examination in physical examination center, the First People's Hospital of Fuquan City from March to August, 2022 (n=697). General information and sleep conditions of the included patients were collected and chronotype was evaluated by single-item question of the Morning and Evening Questionnaire. Unconditional binary Logistic regression model was used to evaluate the association between chronotype and the risk of dyslipidemia. Stratified analysis was also performed by gender, central obesity and late evening snacks among the whole population, and performed by smoking among male population. Sensitivity analysis was used to exclude the effect of shift work. Results Among the included subjects, morningness preference chronotype accounted for 56.4% (n=393), while eveningness preference chronotype accounted for 43.6% (n=304), with 334 cases (47.9%) detected with dyslipidemia. Unconditional binary Logistic regression analysis showed that chronotype was an influencing factor of dyslipidemia〔OR (95%CI) =1.54 (1.10, 2.16) 〕, the risk of hypertriglyceridemia〔OR (95%CI) =1.48 (1.04, 2.12) 〕and low high-density lipoprotein cholesterol〔OR (95%CI) =1.79 (1.18, 2.72) 〕was higher in the adults with eveningness chronotype than those with morningness chronotype (P0.05). The stratified analysis by smoking in male population showed that the risk of low high-density lipoprotein cholesterol was 1.83 times (95%CI: 1.03, 3.26) in adults with eveningness chronotype of that in adults with morningness chronotype in smoking population (P0.05) . Conclusion Eveningness preference chronotype may be a risk factor for dyslipidemia in adults aged 40-65 years, and the associations between dyslipidemia and chronotype may vary across populations with different gender, central obesity, late evening snacks, and smoking status.

Objective To observe the clinical efficacy of CT-guided pulsed radiofrequency combined with platelet-rich plasma （PRP） in the treatment of postherpetic neuralgia. Methods Sixty patients with postherpetic neuralgia were divided into the pulsed radiofrequency plusglucocorticoid group （glucocorticoid group） and pulsed radiofrequency plus PRP group （PRP group） using the random number table method， with 30 patients in each group. The pain visual analogue score （VAS）， Pittsburgh sleep quality index （PSQI）， the average temperature difference （∆T） between the skin lesion area and the corresponding healthy skin area of all patients in two groups were observed before treatment， 1 d， 2 weeks， 4 weeks and 3 months after treatment， respectively. The incidence of complications was also recorded. Results The VAS score and PSQI at 1 d， 2 weeks， 4 weeks and 3 months after treatment were significantly improved compared to those before treatment in two groups （all P < 0.05）. In addition， the ∆T at 4 weeks and 3 months after treatment were significantly improved than those before treatment in two groups （all P < 0.05）. At 3 months after treatment， the VAS score and PSQI in the PRP group were significantly lower than those in the glucocorticoid group （both P < 0.05）. At 1 day， 2 weeks， 4 weeks and 3 months after treatment， the ∆T in the PRP group were significantly lower than those in the glucocorticoid group （all P < 0.05）. No severe adverse reactions occurred in two groups. Conclusions CT-guided pulsed radiofrequency combined with PRP can effectively treat postherpetic neuralgia， and the therapeutic effect is better than that of traditional pulsed radiofrequency combined with glucocorticoid therapy.

Background People with normal weight obesity (NWO) are prone to cardiovascular diseases in their middle and old age. High-intensity interval training (HIIT) has been demonstrated to effectively improve cardiovascular health. However, whether HIIT can decrease the risk of cardiovascular diseases in NWO population is not clear. Objective To explore the effects of HIIT on the advanced glycation end-products (AGEs) and the risk of cardiovascular disease in NWO female university students. Methods From November to December 2020, 137 female college students were recruited in Shanghai University of Medicine & Health Sciences, among whom 40 NWO cases were screened out as subjects by the Asian female NWO standard. They were equally and randomly divided into a control group (n=20) and a HIIT intervention group (n=20) to receive no interventions or weekly five-day interventions, for consecutive four weeks after one-week adaptive training. Body weight, body mass index (BMI) , body fat percentage (BF%) , visceral fat level (VFL) , visceral fat area (VFA) , waist circumference, levels of four blood lipids 〔high-density lipoprotein (HDL) , low-density lipoprotein (LDL) , triglyceride (TG) , and total cholesterol (TC) 〕, cardiovascular disease risk (assessed by the China-PAR model) , AGEs, and fasting blood glucose of two groups were observed before and after intervention. The correlation between AGEs and cardiovascular disease risk was analyzed. Results Except for 10 dropouts, the remaining 30 cases (13 in the control group and 17 in the HIIT intervention group) were finally included for analysis. After intervention, the average BMI, BF%, VFA, VFL, waist circumference, TC/HDL ratio, LDL/HDL ratio, TG/HDL ratio, AGEs and fasting blood glucose in HIIT intervention group were lower than those in control group (P

Background Bariatric surgery is the effective treatment for obesity, however, the effect of surgery on patients' psychological status is still unclear. Objective To investigate the treatment effects of bariatric surgery on patients' psychological status one year after the surgery. Methods This is a retrospective cross-sectional study. This study selected 172 patients who underwent bariatric surgery in the department of general surgery, First Affiliated Hospital of Nanjing Medical University during June 2019 to June 2020, and collected their clinical data. The indicators of the treatment effects of bariatric surgery include body composition indicators〔Weight, Body mass index (BMI) , Percentage of excess weight loss (EWL%) , Body muscle mass (BM) , Body fat mass (BF) , Visceral fat (VSF) , metabolism-related biochemical indexes〔Alanine aminotransferase (ALT) , Aspartate aminotransferase (AST) , Total protein (TP) , Albumin (ALB) 〕, preoperative comorbidities, relief of comorbidities after surgery, postoperative complications, postoperative complaints, surgery methods; Indicators of the postoperative psychological status include quality of life, perceived stress, general well-being and satisfaction degree of surgery. This study used the12-item Short Form Survey (SF-12) , Chinese version of the Perceived Stress Scale (CPSS) , General Well-being Schedule (GWS) , Questionnaire of Bariatric Surgery Patient' Satisfaction Survey to investigate the psychological status. This study used the Pearson correlation analysis and Spearman rank correlation analysis to explore the correlation between body composition indicators and metabolic-related biochemical indexes and postoperative psychological status, used the multivariate linear regression analysis to explore the factors that affect postoperative psychological status. Results One year after surgery, EWL% was (82.7±31.7) %, and BMI decreased by (10.3±4.3) kg/m2. 96 patients (55.8%) had metabolic-related comorbidities such as type 2 diabetes mellitus, hypertension, fatty liver before surgery, 48 patients (27.9%) achieved complete remission, 30 patients (17.4%) achieved partial remission, and 18 patients (10.5%) had no remission after surgery. Patients'weight, BMI, BM, BF, VSF, ALT, AST were lower than those before surgery, the TP and ALB were higher than those before surgery (P

Objective To deepen the understanding of clinicians for giant subgaleal hematoma complicated with intraorbital hematoma as the first presentation of chronic myeloid leukemia in chronic phase （CML-CP）. Methods The diagnosis and treatment of one case of giant subgaleal hematoma complicated with intraorbital hematoma as the first presentation of CML were reported. Literature review was conducted by using the keywords of subgaleal hematoma and chronic myeloid leukemia in English and Chinese from PubMed, Wanfang Data, Chongqing VIP, SinoMed and CNKI.Results The male patient was aged 14 years old. Skull MRI showed subgaleal hematoma complicated with intraorbital hematoma. He was diagnosed with CML-CP by myelogram analysis. He received ultrasound-guided hematoma puncture with pressure dressing, given with leukapheresis, hydroxyurea, cytarabine and imatinib, a tyrosine kinase inhibitor. During 2-year follow-up, he obtained stable condition and normal quality of life. Two cases of CML presenting with subgaleal hematoma as the initial manifestation were retrieved. One case received cranial CT scan and found no abnormality, and CT scan of the other case prompted subgaleal hematoma; one case underwent hematoma puncture combined with pressure dressing, and the other case received incision and drainage of subgaleal hematoma. Fair clinical prognosis was achieved in two cases. Conclusions CML-CP patients presenting with giant subgaleal hematoma complicated with intraorbital hematoma should promptly receive hematoma puncture in combination with chemotherapy and leukapheresis, etc. In addition, tyrosine kinase inhibitor should be promptly given to enhance clinical prognosis.

Objective To investigate the role of arachidonic acid (AA) metabolism-related endoplasmic reticulum genes in the development of HCC in a mouse hepatocellular carcinoma (HCC) microenvironment. Methods The function of differentially expressed endoplasmic reticulum membrane genes (ADEGs) involved in AA metabolism was analyzed by RNA-seq and bioinformatics using AA metabolism-related genes as the background, tumor tissues and paracancer tissues of mice were collect as the sample materials, and the expression of ADEGs was verified by RT-qPCR. Results There was a total of 35 ADEGs in HCC (gene expression in per million per thousand transcripts in sequencing base sequencing contained in the base sequence fragment number (FPKM) ≥2 or ≤0.5, and false positive rate (FDR) was ≤0.05), they were involved in the two biological applications (BPs), five cellcomponents (CCs), nine molecular functions(MFs), a protein loci sequence characteristics (US) and six(KPs) signal channel. The function of these genes was mainly focused on the endoplasmic reticulum membrane, especially the effect of iron ion binding(IIB)on the epoxygenase P450 pathway (EPP). Further analysis revealed that ADEGs in IIB had extensive single nucleotide site variation (SNV) and insertion and deletion (INDEL) in the HCC microenvironment, and its occurrence frequency was positively correlated with gene expression (r=0.83). Conclusions ADEGs in HCC microenvironment may cause EPP abnormalities mainly through IIB in the endoplasmic reticulum, thus playing an important role in the development and progression of HCC, SNV and INDEL may be important ways to regulate gene expression.

TP53 is the most commonly mutated gene in head and neck cancer (HNSCC), with mutations being associated with resistance to conventional therapy. Restoring normal p53 function has previously been investigated via the use of RITA (reactivation of p53 and induction of tumor cell apoptosis), a small molecule that induces a conformational change in p53, leading to activation of its downstream targets. In the current study we found that RITA indeed exerts significant effects in HNSCC cells. However, in this model, we found that a significant outcome of RITA treatment was accelerated senescence. RITA-induced senescence in a variety of p53 backgrounds, including p53 null cells. Also, inhibition of p53 expression did not appear to significantly inhibit RITA-induced senescence. Thus, this phenomenon appears to be partially p53-independent. Additionally, RITA-induced senescence appears to be partially mediated by activation of the DNA damage response and SIRT1 (Silent information regulator T1) inhibition, with a synergistic effect seen by combining either ionizing radiation or SIRT1 inhibition with RITA treatment. These data point toward a novel mechanism of RITA function as well as hint to its possible therapeutic benefit in HNSCC.

Notch signaling involves ligand-receptor interactions through direct cell-cell contact. Multiple Notch receptors and ligands are expressed in the epidermis and hair follicles during embryonic development and the adult stage. Although Notch signaling plays an important role in regulating differentiation of the epidermis and hair follicles, it remains unclear how Notch signaling participates in late-stage epidermal differentiation and postnatal hair cycle homeostasis.We applied Cre/loxP system to generate conditional gene targeted mice that allow inactivation of critical components of Notch signaling pathway in the skin. Rbpj, the core component of all four Notch receptors, and Pofut1, an essential factor for ligand-receptor interactions, were inactivated in hair follicle lineages and suprabasal layer of the epidermis using the Tgfb3-Cre mouse line. Rbpj conditional inactivation resulted in granular parakeratosis and reactive epidermal hyperplasia. Pofut1 conditional inactivation led to ultrastructural abnormalities in the granular layer and altered filaggrin processing in the epidermis, suggesting a perturbation of the granular layer differentiation. Disruption of Pofut1 in hair follicle lineages resulted in aberrant telogen morphology, a decrease of bulge stem cell markers, and a concomitant increase of K14-positive keratinocytes in the isthmus of mutant hair follicles. Pofut1-deficent hair follicles displayed a delay in anagen re-entry and dysregulation of proliferation and apoptosis during the hair cycle transition. Moreover, increased DNA double stand breaks were detected in Pofut1-deficent hair follicles, and real time PCR analyses on bulge keratinocytes isolated by FACS revealed an induction of DNA damage response and a paucity of DNA repair machinery in mutant bulge keratinocytes.our data reveal a role for Notch signaling in regulating late-stage epidermal differentiation. Notch signaling is required for postnatal hair cycle homeostasis by maintaining proper proliferation and differentiation of hair follicle stem cells.