OBJECTIVE To establish a multi-index quantitative detection method， and to evaluate the quality difference of Gleditsia sinensis from different producing areas. METHODS The contents of protocatechuic acid， vanillic acid， isoscopoletin， scoparone， isovitexin， fustin， taxifolin， fisetin， quercetin， kaempferol， echinocystic acid， betulinic acid， β -sitosterol and stigmasterol were detected by high performance liquid chromatography-quantitative analysis of multi-components by single marker （HPLC-QAMS）. The chromatographic column was Kromasil C18， the mobile phase was 0.2% phosphoric acid-acetonitrile solution （gradient elution）， the detection wavelengths were 254， 360， 210 nm for different index components， the column temperature was 30 ℃ ， the flow rate was 1.0 mL/min， and the sample injection volume was 10 μL. The contents of extract and total ash were detected according to the method of Chinese Pharmacopoeia. The quality differences of 30 batches of G. sinensis （No. S1-S30） from different producing areas were evaluated by chemometrics， weighted technique for order preference by similarity to an ideal solution （TOPSIS） analysis and Logistic regression model. RESULTS The linear ranges of 14 components were 1.55-77.50， 0.71- 35.50， 0.28-14.00， 0.96-48.00， 1.77-88.50， 0.09-4.50， 4.65-232.50， 1.49-74.50， 0.37-18.50， 1.18-59.00， 7.35-367.50， 3.58- 179.00， 0.49-24.50 and 0.21-10.50 μg/mL， respectively （all r＞0.999）. The RSDs of precision， stability （24 h） and repeatability were less than 2.00%； the average recoveries were 96.99%-100.13% （all RSDs＜2.00%）， and the relative correction factor had good repeatability. The contents of extract and total ash were Δ 基金项目 湖北省中医药科研立项青年人才项目 （No. 4.2%-12.5% and 0.5%-2.3%， respectively. There was no ZY2019Q014） significant difference in the content of 14 components measured by QAMS method and external standard method （P＞0.05）. The results of chemometrics showed that 30 batches of samples were clustered into 3 categories： S1 to S11 form one category， S12 to S20 form another category， and S21 to S30 constitute the third category. Echinocystic acid， betulinic acid， taxifolin， kaempferol， isovitexin， scoparone and protocatechuic acid may be the differential components affecting the quality of G. sinensis from different producing areas. The analysis results of the weighted TOPSIS method revealed that relative closeness （Jb） for 30 batches of G. sinensis ranged from 0.144 5 to 0.721 8， with S27 achieving the highest value （Jb） of 0.721 8. The analysis results of the Logistic regression model showed that S21-S30 batches of samples were of superior grade， S1-S11 were of intermediate grade， and S12-S20 were of inferior grade. CONCLUSIONS The established HPLC-QAMS method is simple and accurate. The comprehensive evaluation method is objective and comprehensive， and can be used to evaluate the quality difference of G. sinensis from different producing areas.

BackgroundMigraine is a common chronic neurological disease， and patent foramen ovale （PFO） has been closely associated with migraine. Current research primarily focuses on the pathological mechanism and the therapeutic effects of interventional closure， with limited attention paid to the impact of PFO on sleep quality in migraine patients. ObjectiveTo compare the difference in sleep quality between PFO-positive and PFO-negative migraine patients， and to analyzes influencing factors of sleep quality in PFO-positive migraine patients， so as to provide references for clinical interventions to improve sleep quality in PFO-positive migraine patients. MethodsA total of 673 migraine patients who met the diagnostic criteria of migraine in the International Classification of Headache Disorders， third edition （ICHD-3）， and all patients underwent contrast-enhanced transcranial Doppler （c-TCD） and transthoracic echocardiographic right heart contrast echocardiography （cTTE） in the Third Hospital of Mianyang from January 2020 to October 2024. Basic demographic data were collected using a self-designed questionnaire， headache severity was assessed with the Visual Analogue Scale （VAS）， and sleep quality was invaluated using the Pittsburgh Sleep Quality Index （PSQI）. PFO patients was diagnosed through c-TCD combined with c-TTE. Binary logistic regression analysis was employed to examine the influencing factors of sleep quality in PFO-positive migraine patients. ResultsA total of 673 （100.00%） migraine patients were enrolled， including 223 PFO-positive cases （33.14%） and 450 PFO-negative cases（66.86%）. The PFO-positive group showed significantly more severe headache severity （χ²=15.799， P<0.01） and poorer sleep quality （χ²=14.377， P<0.01） compared with PFO-negative group. PFO-positive patients demonstrated significantly higher barrier factor scores of sleep quality， sleep latency， sleep efficiency， sleep disturbance， hypnotic medication use， and daytime dysfunction compared with PFO-negative counterparts （t=3.634， 3.269， 2.785， 3.428， 2.907， 3.637， Bonferroni adjust P<0.05/7=0.007）.By contrast， no significant difference was noted in sleep duration scores between the two groups（t=2.349， Bonferroni adjust P>0.05/7=0.007）.The Binary Logistic regression analysis revealed that age （OR=1.021， 95% CI： 1.001~1.041）， headache severity （OR=6.030， 95% CI： 4.085~8.901）， and PFO grade （OR=1.893，95% CI： 1.288~2.784）were significant influencing factors for sleep quality in migraine patients with PFO. ConclusionMigraine patients with PFO-positive exhibited poorer sleep quality compared wtih PFO-negative patients. Older age， higher headache servity， and more severe PFO grade are identified as risk factors for impaired sleep quality in PFO-positive migraine patients.

OBJECTIVE To comprehensively evaluate the quality of Yifei qinghua ointment by multi-component quantitative analysis combined with chemometrics and entropy weight-technique for order preference by similarity to ideal solution （TOPSIS） method. METHODS The contents of lobetyolin， syringin， calycosin 7-O-β-D-glucopyranoside， ononin， astraisoflavan-7-O-β-D- glucoside， isomucronulatol 7-O-glucoside， astragaloside Ⅳ ， deapi-platycoside E， platycoside E， platycodin D3， feretoside， asperulosidic acid， asperuloside， methylophiopogonanone A and methylophiopogonanone B in 14 batches of Yifei qinghua ointment （S1-S14） were determined by high-performance liquid chromatography method. Then， the quality of 14 batches of Yifei qinghua ointment was analyzed by chemometrics （principal component analysis and orthogonal partial least-squares discriminant analysis） and entropy weight TOPSIS method. RESULTS The results of chemometrics showed that 14 batches of Yifei qinghua ointment could be clustered into three categories， S1-S6 as the first category， S7-S10 as the second category， and S11-S14 as the third category. The values of variable importance for projection of calycosin 7-O-β-D-glucopyranoside， ononin， feretoside， astragaloside Ⅳ， astraisoflavan-7-O-β-D-glucoside， lobetyolin， methylophiopogonanone A and platycoside E were higher than 1. The results of the entropy weight TOPSIS method showed that the Euclidean closeness of the optimal solution of 14 batches of Yifei qinghua ointment were between 0.152 9 and 0.736 6， and that of sample S14 was the highest （0.736 6）. CONCLUSIONS Among 14 batches of Yifei qinghua ointment， sample S14 has the best quality， and 8 components such as calycosin 7-O-β-D-glucopyranoside and ononin may be differential markers affecting the quality of Yifei qinghua ointment.

Objective To investigate the mechanism and clinical significance of miR-18a-5p and retinoid acid receptor-related orphan receptor-α(RORA)in the proliferation and progression of colorectal cancer(CRC)cells.Methods The expressions of miR-18a-5p and RORA in CRC cells and tissues were detected via qRT-PCR,FISH,and IHC.Cell proliferation capability was detected through EdU and CFSE assay,cell apoptosis by flow cytometry assay,and cell migration and invasion abilities by cell scratch and Transwell invasion assays,respectively.The targeted regulation of miR-18a-5p on RORA was further verified via dual-luciferase reporter assay,cell function rescue test,RT-PCR,and Western blot assay.Finally,bioinformatics was used to explore the molecular mechanism of miR-18a-5p promoting malignant proliferation,invasion,and progression of CRC via regulating RORA.Results miR-18a-5p exhibited a high expression in CRC tissues and cells(P<0.05)and promoted the proliferation,migration,and invasion of CRC cells(P<0.05).In addition,RORA served as the target gene of miR-18a-5p,and its overexpression effectively reduced the promoting function of miR-18a-5p in the malignant biological phenotype of CRC cells(P<0.05).The expression of RORA in CRC tissues showed a significantly positively correlation with the infiltration of CD8+T cells and the expression of its surface marker protein CD8A.Conclusion The targeted regulation of RORA by miR-18a-5p promotes the proliferation and progression of CRC.The miR-18a-5p/RORA regulatory pathway possibly contributes to the immune microenvironment of CRC,which can be a potential therapeutic target for CRC.

Objective:To evaluate the role of ketamine in postoperative cognitive dysfunction (POCD) and to clarify the association with subdiaphragmatic vagus nerve in mice.Methods:One hundred and forty-four SPF healthy male C57BL/6J mice, aged 18 months, weighing 32-35 g, were divided into 8 groups ( n=18 each) using a random number table method: sham operation group (group C), surgery group (group S), ketamine + surgery group (group SK), ketamine + surgery + subdiaphragmatic vagotomy group (group SK+ SDV), pseudo germ-free mice+ normal saline group (group GM+ V), pseudo germ-free mice that received fecal microbiota transplantation (FMT) from group S mice group (group GM+ S), pseudo germ-free mice that received FMT from group SK mice group (group GM+ SK), and pseudo germ-free mice received subdiaphragmatic vagotomy and FMT from group SK mice group (group GM+ SDV+ SK). Tibial fracture internal fixation was performed under anesthesia with 2.0% isoflurane. Ketamine 50 mg/kg was intraoperatively administered at the beginning of the suture in group SK. The fecal samples were collected at 24 h after surgery to prepare fecal bacteria filtrate in S and SK groups. The dorsal and ventral branches of subdiaphragmatic vagus nerve were cut prior to ketamine administration in SK+ SDV group and prior to FMT in GM+ SDV+ SK group. Broad-spectrum antibiotics dissolved in drinking water were given ad libitum to mice for 14 consecutive days at 2 weeks before FMT or subdiaphragmatic vagotomy and replaced once every 2 days to establish the pseudo germ-free model. Pseudo germ-free mice were gavaged with normal saline or fecal suspension 200 μl obtained from mice for 14 consecutive days at fixed time starting from 14 days after antibiotic intervention in GM+ SK and GM+ SDV+ SK groups. While normal saline was given instead for 14 consecutive days in GM+ V group. The fecal samples were collected after tibial fracture internal fixation or at 24 h after completion of FMT for 16S rRNA gene sequence analysis. The contents of interleukin-6 (IL-6), IL-17, tumor necrosis factor-alpha (TNF-α), IL-4 and IL-10 in the hippocampus were measured by enzyme linked-immuno-sorbent assay at 24 h after surgery or FMT. The spatial memory and learning ability was assessed by the Morris water maze test at 24 h after surgery or FMT. Results:Compared with group Sham, Simpson′s diversity index, Shannon index and Ace index were significantly decreased, the contents of IL-6, IL-17 and TNF-α were increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group S ( P<0.05). Compared with group S, Simpson′s diversity index, Shannon index and Ace index were significantly increased, the contents of IL-6, IL-17 and TNF-α were decreased, contents of IL-4 and IL-10 were increased, the escape latency in the training and testing phases and swimming distance were shortened, and the time spent in the target quadrant was prolonged in group SK ( P<0.05). Compared with group SK, Simpson′s diversity index, Shannon index and Ace index were significantly decreased, the contents of IL-6, IL-17 and TNF-α were increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group SK+ SDV ( P<0.05). Compared with group GM+ V, the contents of IL-6, IL-17 and TNF-α were significantly increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group GM+ S ( P<0.05). Compared with group GM+ S, the contents of IL-6, IL-17 and TNF-α were significantly decreased, contents of IL-4 and IL-10 were increased, the escape latency in the training and testing phases and swimming distance were shortened, and the time spent in the target quadrant was prolonged in group GM+ S ( P<0.05). Compared with group GM+ SK, the contents of IL-6, IL-17 and TNF-α were significantly increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group GM+ SDV+ SK ( P<0.05). Conclusions:Ketamine can improve intestinal flora disorders and reduce POCD in mice, and the mechanism may be related to subdiaphragmatic vagal nerve conduction.

Objective:To investigate the workflow, feasibility and advantages of respiratory navigator-guided stereotactic body radiation therapy (SBRT) of liver malignancies on the magnetic resonance linear accelerator (MR-linac).Methods:Clinical data of 10 patients with liver cancer treated with respiratory navigator-guided SBRT on the MR-linac from September to December 2021 were analyzed retrospectively. All patients underwent CT and MR simulated localization, and plain, enhanced and 4D CT scan, and T 1 3D MR and T 2 3D MR images were collected. The expiratory 4D CT was chosen to design the reference plan. The T 2 3D navigator MR image (end-exhalation) was collected before treatment, the target position was adjusted or the target shape was modified in combination with the real-time monitoring 2D MR image and appropriate online adaptive planning process was selected. Then, the ability of CT, T 2 3D and T 2 3D navigator MR images to display the tumor was evaluated by naked eye. The changes of target volume were calculated. Dosimetric differences between the adaptive and reference plans were compared. The efficacy and adverse reactions of patients were evaluated. Results:In the free breathing state, the T 2 3D navigator MR image was significantly better than T 2 3D MR image to clearly display the tumor and its boundary. The adaptive plans of adapt-to-position (ATP) and adapt-to-shape (ATS) adopted by 10 patients was 37 times and 22 times respectively. The tumor subsided significantly in 3 patients. The average target conformal index (CI) of the adaptive plans was no different from that of the reference plans, but the gradient index (GI) was higher ( P<0.05), especially in the ATS plans. Compared to the reference plans, the normal liver V 5 Gy, V 10 Gy and D mean were almost the same, but the average MU was increased with a significant difference in the ATP adaptive plans ( P<0.05). The average of MU, segments and normal liver D mean and V 10 Gy in the ATS adaptive plans were lower than those in the reference plans, and the liver V 5 Gy was slightly increased. Seven patients were evaluated after 1 month and 3 months. The local control of lesions was promising. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusion:Respiratory navigator on MR-linac improves the visual clarity of tumors and online MR images, and shows its advantages to guide the adaptive precision radiotherapy of liver tumors, especially in SBRT.

Objective:To study the impact on dose accuracy for the treatment planning by manually assigning accurate electron density for CT image-based tumor tissues and organs at risk.Methods:Twenty cases of retrospective postoperative cervical cancer radiotherapy plans were selected. The body electron density of the corresponding organs was derived from the ICRU 46 report and assigned in the treatment planning system (Monaco5.11, Sweden), including the bladder, rectum, intestine, kidney, spinal cord, femoral head, and ilium. The original plans were double-arc volumetric modulated arc therapy plan (360° VMAT), using Monte Carlo algorithm, the calculation grid was 0.3 cm × 0.3 cm × 0.3 cm, and the minimum subfield width was 0.6 cm. Keep the original plan fluence unchanged and recalculate the dose to generate a new plan. The two-dimensional dose distribution and dose-volume histogram (DVH) were used to compare the differences between the two plans. The difference was compared between the two group plans by using the dosimetry parameters and DVH two dimension curve.Results:For the planning of assigning bulk electron density (Plan RED), the deviation of the patient′s target dose parameters and the original plan (Plan ref) was <2%, and the average deviation of all target regions D2, D98, Dmean was < 0.7%, only 2 of the 180 data were between 2% and 3%. The average deviation of V20, V30, D1 cm 3, Dmean of the bladder, rectum, and small intestine, the original Plan ref was less than 0.6%, and 4 out of 240 data had values > 2%. Plan RED′s average hop count was 0.9% higher than Plan ref, and the total number of subfields remains unchanged. The planned dose generated by manually assigning the electron density in Plan RED was higher than that in Plan ref, but met the clinical requirements. The two-dimensional curves of the DVH diagram for targets and OARs almost completely overlapped, and there was no obvious difference in the dose distribution diagram of the same cross section. The statistical result of all parameters showed that the difference in planned dose parameters between the two groups was not statistically significant( P>0.05). Conclusions:The overall deviation of dose accuracy between Plan RED and Plan ref is <2%, which meets the clinical requirements and provides a reference for realizing MRI-only treatment planning.

Objective:To evaluate the effects of intraoperative fluid therapy guided by different stroke volume variation (SVV)s on bleeding during laparoscopic hepatolobectomy and postoperative renal function.Methods:A total of 135 American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients of both sexes, aged 25-64 yr, scheduled for elective laparoscopic hepatolobectomy under general anesthesia, were divided into 3 groups ( n=45 each) using a random number table method: low SVV group (group L), medium SVV group (group M) and high SVV group (group H). In group L, group M and group H, SVVs were maintained at 10%-15%, 16%-20% and more than 21%, respectively.Before surgery and at 1, 3 and 5 days after the surgery, blood samples from the peripheral vein were taken for determination of serum blood urea nitrogen, creatinine and procalcitonin (PCT) concentrations.The occurrence of conversion to laparotomy, intraoperative volume of blood loss, volume of blood transfused, urine volume, operation duration, length of hospital stay and time to first flatus were recorded.On admission to the operating room (T 0), at skin incision (T 1), at the beginning of resection of the liver (T 2), after resection of the lobes of the liver (T 3) and at the end of the surgery (T 4), mean arterial pressure (MAP), heart rate (HR) and lactic acid (Lac) were recorded.The consumption of intraoperative norepinephrine, hypotension, arrhythmia and postoperative adverse reactions were recorded. Results:Compared with group L, the intraoperative volume of blood loss and consumption of intraoperative norepinephrine in group M and intraoperative volume of blood loss, the total amount of fluid infused and urine volume in group H were significantly decreased, consumption of furosemide and nitroglycerin in group H and the total amount of red blood cells infused in M and H groups were increased, length of hospital stay and time to first flatus in group M were shortened, concentration of serum PCT at 1 day after surgery was decreased in group M, MAP at T 3, 4 was increased in group M, and Lac at T 2-4 was increased in group H ( P<0.05). Compared with group M, the intraoperative volume of blood loss, consumption of intraoperative norepinephrine and consumption of furosemide and nitroglycerin were significantly increased, the total amount of fluid infused and urine volume were decreased, length of hospital stay and time to first flatus in group M were prolonged, concentration of serum PCT at 1 day after surgery was increased, MAP at T 3, 4 was decreased in group M, and Lac at T 2-4 was increased in group H ( P<0.05). There was no significant difference in the incidence of postoperative adverse reactions and intraoperative hypotension and arrhythmia among the 3 groups ( P>0.05). Conclusion:Intraoperative fluid therapy guided by SVV at 16%-20% during laparoscopic hepatolobectomy can decrease the intraoperative volume of blood loss and has less effect on renal function, which is helpful for postoperative outcomes.

Objective:To investigate the safety and mid-term efficacy of robotic versus laparoscopic total mesorectal excision surgery in rectal cancer.Methods:A total of 240 patients were diagnosed with rectal cancer at the Anorectal Department of Gansu Provincial Hospital from Aug 2015 to Mar 2021, 112 patients underwent laparoscopic total mesorectal excision (L-TME group) and 128 patients did robotic-assisted total mesorectal excision (R-TME group).Results:Compared to the R-TME group, the L-TME group had higher conversion rate (5.4% vs. 0.8%, χ2=4.417, P=0.036), higher incidence of complications (32.1% vs. 17.2%, χ2=7.290, P=0.007), higher circumferential resection margin involvement (7.1% vs. 1.6%, χ2=4.658, P=0.031), lower 3-year DFS and OS(74.1% vs. 85.2%, χ2=4.962, P=0.026) and (81.3% vs. 91.4%, χ2=5.494, P=0.019), lower 3-year DFS and OS in AJCC stage Ⅲ(52.5% vs. 76.1%, χ2=5.799, P=0.016) and (65.0% vs. 84.8%, χ2=4.787, P=0.029). Conclusion:R-TME can achieve better oncological outcomes and is more beneficial for RC patients compared with L-TME, especially for those with stage Ⅲ rectal cancers.

OBJECTIVE: Discuss the working ideas of the dynamic adjustment mechanism of medical device classification in the United States, and provide reference for the construction of medical device related mechanisms in China. METHODS: Collect and interpret the documents of regulatory background, procedures and orders of the dynamic adjustment mechanism of the medical device classification in the United States, and summarize the overall situation and specific cases of the medical device classification adjustment under this mechanism in recent years. RESULTS: The US work idea of the medical device classification dynamic adjustment mechanism is based on the latest valid scientific evidence, conducting risk analysis and identification, and determining the corresponding measures. CONCLUSIONS During the adjustment process, industry stakeholders have repeatedly discussed and achieved final agreement. Its procedures and working ideas can be used as a reference for China's work.
China ; United States ; United States Food and Drug Administration