[摘 要] 目的：探讨安罗替尼联合免疫检查点抑制剂（ICI）作为一线方案治疗晚期肺鳞状细胞癌（LUSC）的有效性及安全性。方法：采用单中心回顾性队列设计，连续纳入2018年10月至2023年12月福建省福州肺科医院收治的37例初治晚期LUSC患者。所有患者接受安罗替尼（剂量为8、10或12 mg/d，用药2周/停药1周）联合ICI治疗。主要终点为无进展生存期（PFS），次要终点包括客观缓解率（ORR）、疾病控制率（DCR）及治疗相关不良事件（TRAE）。结果：全组患者中位随访15.2个月，ORR达54.1%（20/37），DCR为97.3%（36/37），中位PFS为11.8个月（95%CI：8.3~NA），12个月PFS率为48.6%。探索性亚组分析显示：安罗替尼12 mg剂量组的中位PFS（未达到 vs 7.5个月，HR = 0.09，95%CI：0.01~0.67，P < 0.01）及ORR（100% vs 42.9%，P < 0.01）均显著优于8/10 mg组。分期分层显示ⅢB/ⅢC期患者ORR显著优于Ⅳ期（84.6% vs 41.7%，P = 0.02）。安全性方面，62.2%（23/37）的患者发生TRAE，以1~2级高血压[29.7%（11/37）]、手足综合征[21.6%（8/37）]为主，3例（8.1%）因3级TRAE终止治疗。结论：安罗替尼联合ICI作为晚期LUSC一线治疗方案具有良好的疗效前景和可管理的安全性。其中，12 mg剂量组在探索性分析中显示出更优疗效的潜在信号，早期分期患者ORR更高。该结果值得开展大规模前瞻性研究进行进一步验证。

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

OBJECTIVES: A ventricular assist device (VAD) is an electromechanical device used to assist cardiac blood circulation, which can be employed for the treatment of end-stage heart failure and is most commonly placed in the left ventricle. Despite enhancing perfusion performance, the implantation of left ventricular assist device (LVAD) transforms the local intraventricular flow and thus may increase the risk of thrombogenesis. This study aims to investigate fluid-particle interactions and thromboembolic risk under different LVAD configurations using three-dimensional (3D) reconstruction models, focusing on the effects of outflow tract orientation and blood flow rates. METHODS: A patient-specific end-diastolic 3D reconstruction model was initially constructed in stereo lithography (STL) format using Mimics software based on CT images. Transient numerical simulations were performed to analyze fluid-particle interactions and thromboembolic risks for LVAD with varying outflow tract orientations under 2 flow rates (4 L/min and 5 L/min), using particles of uniform size (2 mm), and a blood flow rate optimization protocol was implemented for this patient. RESULTS: When the LVAD flow rate was 5 L/min, helicity and flow stagnation of the blood flow increased the particle residence time (RT) and the risk of thrombogenesis of the aortic root. The percentage of particles traveling toward the brachiocephalic trunk was up to 20.33%. When the LVAD flow rate was 4 L/min, blood turbulence in the aorta was reduced, the RT of blood particles was shortened, and then the percentage of particles traveling toward the brachiocephalic trunk decreased to 10.54%. When the LVAD blood flow rate was 5 L/min and the direction of the outflow pipe was optimal, the RT of blood particles was shortened, and then the percentage of particles traveling toward the brachiocephalic trunk decreased to 11.22%. A 18-month follow-up observation of the patient revealed that the LVAD was in good working order and the patient had no complications related to the implantation of LVAD. CONCLUSIONS Implantation of LVAD results in a higher risk of cerebral infarction; When implanting LVAD with the same outflow tract direction, optimizing flow velocity and outflow tract can reduce the risk of cerebral infarction occurrence.
Heart-Assist Devices/adverse effects* ; Humans ; Heart Failure/physiopathology* ; Blood Flow Velocity ; Thromboembolism/prevention & control* ; Models, Cardiovascular ; Heart Ventricles/physiopathology* ; Imaging, Three-Dimensional

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

OBJECTIVES: To investigate the effects of Naoluo Xintong Decoction (NLXTD) on proliferation of rat brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation/reoxygenation (OGD/R) injury and role of the HIF-1α/VEGF pathway in mediating its effect. METHODS: Using a BMEC model of OGD/R, we tested the effects of 10% NLXTD-medicated rat serum, alone or in combination with 2ME2 or 10% NAKL, on cell proliferation, migration, tube-forming ability and permeability using CCK-8 assay, Transwell chamber assay, tube formation assay and permeability assay. Cellular expressions of VEGF and Notch were detected using ELISA and laser confocal immunofluorescence analysis, and the expressions of HIF-1α, VEGFR2, Notch1, ERK and P-ERK1/2 proteins were detected with Western blotting. RESULTS: OGD/R injury significantly decreased viability of BMECs. NLXTD treatment of the cells with OGD/R could significantly promoted cell proliferation, migration and tube formation ability, but these effects were strongly attenuated by application of 2ME2. NLXTD treatment also significantly increased the percentages of VEGF- and Notch-positive cells in the cell models and obviously enhanced the expression levels of HIF-1α, VEGFR2, Notch1 and P-ERK1/2. CONCLUSIONS NLXTD promotes proliferation, migration, and tube formation of rat BMECs after OGD/R injury possibly by activating the HIF-1α/VEGF signaling pathway.
Animals ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Rats ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Glucose ; Brain/blood supply* ; Cells, Cultured ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor Receptor-2/metabolism* ; Oxygen/metabolism* ; Cell Hypoxia

BACKGROUND:Cross-sectional area and fat infiltration are the standard parameters for quantifying paravertebral muscle,but it is too cumbersome and time-consuming to introduce new quantifying indicators. OBJECTIVE:To investigate the relationship between paravertebral muscle and spinopelvic sagittal parameters and the predictive value of lumbar indentation value for sagittal balance in patients with isthmic spondylolisthesis.METHODS:The study included 87 patients diagnosed with spondylolisthesis,all of whom had grade Ⅱ spondylolisthesis according to Meyerding classification,including 40 males and 47 females,with a mean age of (51.4±9.1) years. The sagittal vertical axis,pelvic incidence angle,pelvic inclination angle,sacral inclination angle,lumbar lordosis,thoracic kyphosis,and the difference between pelvic incidence and lumbar lordosis were measured. The total cross-sectional area,functional cross-sectional area,and fat infiltration of lumbar paracolateral muscles were measured. Pearson correlation analysis was used to investigate the correlation between sagittal parameters and paravertebral muscle measurements. Multiple linear regression was used to analyze the effects of lumbar indentation value,age,sex,and body mass index on spinopelvic sagittal balance. The receiver operating characteristic curve was used to find the best cut-off point of the indentation value of the lumbar spine,and the relationship of sagittal vertical axis and pelvic incidence with lumbar lordosis was evaluated.RESULTS AND CONCLUSION:(1) According to Pearson correlation analysis,the total cross-sectional area of the multifidus muscle was significantly correlated with lumbar lordosis (r=0.464,P<0.01) and the difference between pelvic incidence and lumbar lordosis (r=-0.306,P<0.01). The functional cross-sectional area of multifidus muscle was significantly correlated with lumbar lordosis (r=0.367,P<0.01) and the difference between pelvic incidence and lumbar lordosis (r=-0.228,P<0.05). The indentation value of lumbar spine was significantly correlated with the sagittal vertical axis (r=-0.300,P<0.01),lumbar lordosis(P=0.417,P<0.01),thoracic kyphosis (r=0.351,P<0.01),and the difference between pelvic incidence and lumbar lordosis (r=-0.319,P<0.01). (2) According to multiple linear regression analysis,the indentation value of lumbar spine was independently correlated with the difference between pelvic incidence and lumbar lordosis and the sagittal vertical axis. 55％ (11/20) of patients with lumbar indentation value ≤11.5 mm had sagittal vertical axis ≤ 50 mm,while 96％(64/67) of patients with lumbar indentation value>11.5 mm had sagittal vertical axis ≤ 50 mm. 30％ (6/20) of patients with the difference between pelvic incidence and lumbar lordosis ≤ 11.5 mm had the difference between pelvic incidence and lumbar lordosis ≤ 10°,while 66％ (44/67) of patients with lumbar indentation value>11.5 mm had the difference between pelvic incidence and lumbar lordosis ≤ 10°. (3) It is concluded that both total cross-sectional area and functional cross-sectional area were significantly correlated with lumbar lordosis and the difference between pelvic incidence and lumbar lordosis. Lumbar indentation value,as a new indicator for the evaluation of paravertebral degeneration,was independently correlated with the sagittal vertical axis and the difference between pelvic incidence and lumbar lordosis,and had certain predictive value for postoperative sagittal plane correction. It was a simple and practical method for the evaluation of spinopelvic sagittal plane and paravertebral muscle degeneration. The degeneration of the paravertebral muscle is related to spinopelvic sagittal balance.

Objective:To assess the feasibility and efficacy of transperineal laser ablation(TPLA)with single laser fiber in treating benign prostatic obstruction(BPO).Methods:From April 2021 to March 2024,a total of 13 BPO patients were selected from Beijing Friendship Hospital.TPLA was performed using a single laser fiber,which was guided by transrectal biplane ultrasound.The single laser fiber was used to undergo TPLA under the guidance of trans-rectal dual-plane ultrasound.The intraoperative time,ablation time,energy consumption,indwelling time of catheter,and complications were observed.The postoperative 6 months was chosen as the cut-off point of follow-up,and the pre and postoperative changes of international prostate symptom score(IPSS),quality of life index(QoL),prostate volume(PV),residual urine volume(RUV)and the maximum urine flow rate(Qmax)were compared.Results:All 13 patients successfully underwent TPLA with single laser fiber.The average operation time was(55.1±18.3)min,and the average ablation time was(16.3±1.7)min,and average energy consumption was(3951.6±459.7)J,and the median value of indwelling time of catheter was 7(7,10)days.The number of postoperative complication was 2 cases,and both them belonged to Clavien-Dindo grade II complication.At the postoperative 6th month,the IPSS,QoL,PV,Qmax and RUV of all patients were improved,all of which were better than preoperative these indicators,and the differences were significant(t=12.102,-3.228,-3.181,-2.581,-2.936,P<0.05).Conclusion:The application of single laser fiber in conducting TPLA operation is feasibility at technical aspect,and it can achieve the therapeutic goals of improving patients'symptoms and enhancing their quality of life.Although its operational time is slightly longer than that of using multiple fibers simultaneously,it can effectively reduce the cost of expenditure for consumables.

[Purpose]To analyze the incidence and mortality of oral and pharyngeal cancer in can-cer registration areas of Hunan Province in 2021 and the trend changes from 2012 to 2021.[Methods]Data on oral and pharyngeal cancer incidence and mortality from 2012 to 2021 were collected from 78 quality-controlled cancer registries in Hunan Province,with population data sourced from household registration statistics provided by public security authorities.Indicators such as crude incidence and mortality rates,age-standardized incidence and mortality rates by Chinese standard population(ASIRC/ASMRC),and world standard population(ASIRW,ASMRW)in 2021 were calculated.The Chinese standard population(2000 national census)and Segi's world standard population were used for standardization.Joinpoint Regression Program 4.9.0.0 software was used to fit a Log-linear regression model,and the average annual percentage change(AAPC)of ASIRC/ASMRC of oral and pharyngeal cancer from 2012 to 2021 was calculated to analyze the changing trends.[Results]In 2021,the crude incidence rate of oral and pharyngeal cancer in cancer registration areas of Hunan Province was 9.28/105(15.14/105 for males and 3.07/105 for fe-males),with an ASIRC of 6.10/105;the crude mortality rate was 3.75/105(6.19/105 for males and 1.16/105 for females),with an ASMRC of 2.16/105.Both the incidence and mortality rates in male were significantly higher than those in female.Age distribution analysis showed that the incidence rate of oral and pharyngeal cancer increased with age after 30 years old,peaking in the age group of 60～64 years old(22.29/105);the mortality rate continued to rise after 35 years old,reaching the peak in the population aged ≥85 years old(14.52/105).Trend analysis from 2012 to 2021 indicated that the crude incidence rate and ASIRC of oral and pharyngeal cancer increased from 3.50/105 and 2.63/105 in 2012 to 9.28/105 and 6.10/105 in 2021,with AAPC of 12.33％and 10.80％,re-spectively;the crude mortality rate and ASMRC also showed upward trends(AAPC of 9.87％and 7.21％,respectively);all trend changes were statistically significant(all P＜0.05).Sex stratification revealed that the AAPC of ASIRC and ASMRC of oral and pharyngeal cancer in male were higher than those in female(AAPC of ASIRC:12.65％for males vs 4.28％for females;AAPC of ASMRC:8.79％for males vs 4.13％for females).Age-specific trend analysis found that the ASIRC of oral and pharyngeal cancer in the population aged ≤ 44 years old showed an upward trend(AAPC=11.73％,P＜0.001),with the AAPC of male in this group reaching 14.57％;the AAPC of ASIRC for the age groups of 45～64 years old and ≥65 years old were 11.03％and 9.74％,respectively,and the AAPC of ASMRC for these two groups were 10.05％and 8.19％,respectively,with all trend changes being statistically significant(all P＜0.05);there was no statistically significant change in the ASMRC of the population aged ≤44 years old(AAPC=5.66％,P=0.087).[Conclusion]The incidence and mortality rates of oral and pharyngeal cancer in cancer registration areas of Hunan Province remain high and show an upward trend,with a tendency of younger onset.Males and middle-aged and elderly populations are the key focuses of prevention and control.