Objective: To evaluate the effect of community comprehensive management model intervention among patients with dyslipidemia, so as to provide the reference for optimizing community management strategies and improving the target achievement rate for blood lipids among this population. Methods: From May to June 2023, a multi-stage stratified random sampling method was employed to select patients with dyslipidemia from primary healthcare institutions in Jiaxing City, Zhejiang Province. Eligible participants were randomly assigned to either a control group or an intervention group. The control group received routine management, while the intervention group was subjected to a community comprehensive management model in addition to the routine care. Both groups were followed up for 24 months. Data on demographic characteristics, lifestyle behaviors, physical examination indices, and blood biochemical indicators were collected at baseline and after the intervention through questionnaires, physical examinations, and laboratory tests. Changes in obesity rate, central obesity rate, target achievement rates for blood lipids, blood pressure, and blood glucose, as well as lifestyle modifications, were analyzed. Differences between the two groups before and after the intervention were assessed using generalized estimating equations (GEE). Results: The control group consisted of 560 patients, including 303 females (54.11%) and 430 individuals aged ≥65 years (76.79%). The intervention group also included 560 patients, with 300 females (53.57%) and 431 individuals aged ≥65 years (76.96%). Before the intervention, no statistically significant differences were observed between the two groups in terms of gender, age, educational level, history of chronic diseases, and atherosclerotic cardiovascular disease risk stratification (all P>0.05). After 24 months of intervention, interaction effects between group and time were observed for obesity rate, central obesity rate, target achievement rate for blood lipids, target achievement rate for blood glucose, composite target achievement rate, physical activity rate, and medication adherence (all P<0.05). Specifically, the intervention group demonstrated lower rates of obesity and central obesity, and higher target achievement rate of blood lipids, target achievement rate of blood glucose, composite target achievement rate, physical activity rate, and medication adherence compared to the control group. Conclusion The community comprehensive management model contributed to improvements in multiple metabolic parameters (including body weight, waist circumference, blood lipids, and blood glucose) among patients with dyslipidemia, and was associated with increased physical activity rate and medication adherence.

Objective To analyze the clinical significance of subjective visual vertical (SVV) tests at different head deflection angles in assessing utricle function in patients with benign paroxysmal positional vertigo (BPPV). Methods A total of 61 BPPV patients who were treated at the Hearing Impairment and Vertigo Diagnosis and Treatment Center of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from August 2022 to May 2023 were retrospectively included, and 29 healthy adults were selected as controls. SVV tests were performed on all research subjects at different head deflection angles: upright head (0°), left head 45° (L45°), right head 45° (R45°). The test results between the two groups were compared. Results SVV absolute value at R45° in BPPV group was lower than that in the control group (P＝0.003); there was no significant difference in SVV values at 0° and L45° between the two groups. There was no statistical difference in SVV values at different head deflection angles between the control group and the left BPPV group. SVV absolute value at R45° in right BPPV group was lower than that in the control group (P＜0.001); there was no statistical difference in SVV values at 0° and L45° between the two groups. Conclusions SVV test can provide subjective information about the utricle, and SVV tests at different head deflection angles can fine-tune evaluate the function of the utricle in BPPV patients.

ObjectiveThis study sought to investigate the impact of exosomes derived from LoVo cells (LoVo-Exos) in colorectal cancer (CRC) on tumor angiogenesis, as well as to elucidate the potential molecular mechanisms underlying their pro-angiogenic effects. MethodsLoVo-Exos were isolated via ultracentrifugation, and their internalization into recipient human umbilical vein endothelial cells (HUVECs) was visualized using confocal microscopy. The influence of LoVo-Exos on angiogenesis was assessed through an in vitro tube formation assay. Additionally, the pro-angiogenic effects of LoVo-Exos were evaluated in vivo using a matrix gluing assay in mice. To investigate the molecular mechanisms through which LoVo-Exos facilitate angiogenesis, Western blot analysis was employed to examine the transfer of pEGFR by LoVo-Exos into recipient cells. Both Western blot and ELISA were utilized to assess the expression levels of key signaling proteins within the EGFR-ERK pathway, as well as the expression of downstream angiogenic core molecules. Furthermore, the impact of EGFR knockdown and ERK inhibitor treatment on angiogenesis was evaluated, with subsequent analysis of the expression of downstream angiogenic core molecules following these interventions. ResultsConfocal microscopy demonstrated the internalization of LoVo-Exos into HUVECs. In vitro angiogenesis assays further indicated that LoVo-Exos significantly enhanced the formation of tubular structures in HUVECs. Additionally, macroscopic examination of subcutaneous matrix plug formation in mice revealed a substantial increase in vascular-like structures within the matrix plugs following the administration of LoVo-Exos, compared to the PBS control group. Hematoxylin and eosin (HE) staining revealed the presence of erythrocyte-filled microvessels within the matrix plugs combined with LoVo-Exos. Furthermore, immunohistochemical analysis demonstrated the expression of the endothelial cell marker CD31 in these matrix plugs. The presence of CD31-positive cells in the LoVo-Exos-treated matrix plugs was associated with a significant enhancement in the formation of luminal structures. These findings suggest that LoVo-Exos facilitate the in vivo development of vascular-like structures. Subsequent investigations demonstrated that LoVo-Exos facilitated the delivery of pEGFR to HUVEC, thereby enhancing angiogenesis. Conversely, LoVo-Exos with EGFR knockdown exhibited a diminished capacity to promote angiogenesis, an effect that was further attenuated by the ERK phosphorylation inhibitor U0126. Western blot analysis assessing the activation of the EGFR-ERK signaling pathway in HUVEC indicated that LoVo-Exos augmented angiogenesis through the activation of this pathway. Furthermore, analysis of the impact of LoVo-Exos on the expression of downstream angiogenic core molecules revealed an increase in interleukin-8 (IL-8) secretion in HUVEC. The enhancement observed was diminished in LoVo-Exos following EGFR knockdown, and this reduction was counteracted by the ERK phosphorylation inhibitor U0126. ConclusionThe underlying mechanism may involve the delivery of pEGFR in LoVo-Exos to HUVECs, leading to increased IL-8 secretion via the EGFR-ERK signaling pathway, thereby enhancing the angiogenic potential of HUVECs. This finding may offer new insights into the mechanisms underlying cancer metastasis.

ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

Japanese spotted fever(JSF)is an infectious disease caused by Rickettsia japonica,with nonspecific clinical symptoms and a high risk of misdiagnosis.We reported a case of JSF,in which Rickettsia japonica was detected in blood cells by metagenomic next-generation sequencing.The patient recovered after treatment with doxycycline.This report provides a reference for the clinical diagnosis and treatment of JSF.
Humans ; High-Throughput Nucleotide Sequencing ; Metagenomics ; Rickettsia/isolation & purification* ; Spotted Fever Group Rickettsiosis/microbiology*

Objective: To investigate the trend in mortality of injury in Jiaxing City, Zhejiang Province, from 2010 to 2022, so as to provide the evidence for developing injury prevention and intervention strategies. Methods: Data on injury mortality in Jiaxing City from 2010 to 2022 were obtained from the Jiaxing Chronic Disease Monitoring Information Management System. Crude mortality was calculated, and standardized mortality was computed using data of the Sixth National Population Census in 2010. Descriptive analysis of injury mortality and cause of injury death was conducted by gender and age. The average annual percent change (AAPC) was used to analyze the trend in mortality of injury from 2010 to 2022. Results: From 2010 to 2022, the crude injury mortality in Jiaxing City was 79.24/100 000, and the standardized mortality was 47.08/105. The crude injury mortality was higher in males than in females (80.51/100 000 vs. 78.01/100 000, P<0.05). The standardized injury mortality for the total population, males, and females showed significant declining trends (AAPC=-2.011%, -2.373% and -1.542%, all P<0.05). The crude injury mortality increased with age (P<0.05), peaking in the age group of ≥85 years (1 806.46/100 000). Decreasing trends were observed in the age groups of 0-<15 years, 15-<45 years, and 45-<65 years (AAPC=-7.794%, -4.698% and -4.521%, all P<0.05), while no significant trend was found in the age group of ≥65 years. The top five causes of injury death were falls (29.96/100 000), motor vehicle traffic accidents (17.81/100 000), drowning (6.50/100 000), suicide (5.40/100 000), and poisoning (0.69/100 000). Drowning was the leading cause of injury death in the age group of 0-<15 years, while falls were the primary cause in the age group of ≥65 years. Motor vehicle traffic accidents were the top cause of injury death in age groups of 15-<45 years and 45-<65 years. From 2010 to 2022, the standardized mortality of falls showed an upward trend (AAPC=1.094%, P<0.05), while the standardized mortality of motor vehicle traffic accidents, drowning, and suicide demonstrated downward trends (AAPC=-7.576%, -2.745% and -2.786%, all P<0.05). Conclusions The standardized injury mortality in Jiaxing City showed an overall downward trend from 2010 to 2022. Falls were the leading cause of injury death, and particular attention should be paid to the prevention and control of falls among the elderly aged ≥65 years.

Objective:To investigate the efficacy and safety of venetoclax and azacitidine combined with GHA (human granulocyte colony stimulating factor, homoharringtonine and low-dose cytarabine) priming regimen in treatment of patients with relapsed/refractory acute myeloid leukemia.Methods:A retrospective case series study was conducted. Twenty-three patients with relapsed/refractory acute myeloid leukemia (non-acute promyelocytic leukemia) who received treatment with the combination of venetoclax and azacitidine with GHA priming regimen at the Second Affiliated Hospital of Xi'an Jiaotong University from October 2020 to July 2024 were selected, and the treatment efficacy, minimal residual disease (MRD)-negative rate in patients with comprehensive complete remission (cCR) (including complete remission, complete remission with partial hematologic recovery and complete remission with incomplete hematologic recovery) and the adverse reactions were analyzed; patients were followed-up, and their overall survival (OS) was analyzed by using Kaplan-Meier method.Results:The median age of the 23 patients was 60 years (range: 21-79 years), including 10 males and 13 females. The cCR rate for 1 course of treatment was 52.2% (12/23), with 4 cases of MRD negative among cCR patients; 5 cases received 2 courses of treatment, with 3 cases achieving cCR, of which 2 cases were MRD negative; 2 cases received 3 courses of treatment, with 1 case achieving complete remission with incomplete hematologic recovery. Six patients underwent allogeneic hematopoietic stem cell transplantation. The patients were followed up until July 31, 2024, and the median follow-up period was 5.3 months (range: 1.1-41.7 months). Ten cases survived, 12 cases died, 1 case was lost to follow-up, and the median OS time of 23 patients was 7.9 months. The 6-month OS rate was 60.2% (95% CI: 42.7%-84.8%), and the 12-month OS rate was 44.6% (95% CI: 26.8%-74.3%). Common adverse reactions during treatment included infection [69.6% (16/23)], nausea [56.5% (13/23)], febrile neutropenia [52.2% (12/23)], bleeding [52.2% (12/23)], vomiting [34.8% (8/23)], and pneumonia [34.8% (8/23)]. Conclusions:The combination of vinaclotide and azacitidine with GHA priming regimen has certain efficacy and good safety in the treatment of relapsed/refractory acute myeloid leukemia.

Objective To explore the correlation between the actual age and the pulp chamber volume(PCV)and pulp dentinal index(PDI)of the right first molars based on cone beam computed tomog-raphy(CBCT)technology,and to construct an accurate and convenient model for age estimation.Methods CBCT image data of 1 857 Han adults(883 males and 974 females)from the Department of Stomatology,Affiliated Hospital of North Sichuan Medical College were collected.The data were di-vided into training and validation sets at a ratio of 8∶2.A total of 1 485 training samples were used to construct the age estimation model,and 372 samples were used to validate the accuracy of the model.The Mimics 21.0 software was used to measure the PCV and calculate the PDI of the right first molars.Their correlations with age and the differences between different sexes and tooth positions were analyzed.Results Both the PCV and the PDI of the first molars showed strong negative correla-tions with the actual age(r values ranged from 0.82 to 0.89).The differences in PCV and PDI be-tween different sexes and tooth positions were statistically significant(P<0.05).The age estimation model based on PDI was superior to that based on PCV.The model based on the PDI values of the two right first molars(y=73.72-44.15 x3-28.27 x4,where x3 and x4 are the PDI values of the right maxil-lary and mandibular first molars,respectively)was the best,with the R2 of 0.79 and the mean abso-lute error of 4.90 years.Conclusion Both PCV and PDI of the first molars are effective indicators for age estimation.The age estimation model based on the PDI is more convenient and accurate than that based on the PCV,providing a more effective method for age estimation in forensic practice.