Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Rheumatoid arthritis(RA)is an autoimmune disease with the basic pathological manifestation of synovial inflammation.Symmetric poly-articular pain and swelling are the main symptoms in clinical practice,and even extra-articular manifestations and comorbidities such as interstitial fibrosis and coronary artery disease are triggered,which seriously affect the quality of life of patients.Traditional Chinese medicine(TCM)has achieved good clinical efficacy in the prevention and treatment of RA with the advantages of multi-pathway,multi-target,multi-component,and less toxic side effects,and plays an important role in the treatment of RA.Recently,many studies have demonstrated that Chinese medicine monomers and Chinese herbal compound can control inflammation,reduce angiogenesis,induce apoptosis of synovial fibroblasts,and inhibit their proliferation,invasion and migration by regulating the PI3K/Akt signaling pathway,so as to play a key role in the treatment of RA.For this reason,the article summarizes current knowledge regarding the PI3K/Akt signaling pathway and its role in RA,as well as summarizes the current research progress of TCM in the treatment of RA by regulating the PI3K/Akt signaling pathway.The aim of this review is to provide theoretical bases for the prevention and treatment of RA and the development of new drugs.

Objective To investigate the clinical efficacy of transjugular intrahepatic portosystemic shunt(TIPS)combined with indwelling catheter-directed thrombolysis for the treatment of portal vein thrombosis(PVT).Methods The clinical efficacy of 307 patients with portal hypertension complicated by PVT,who received successful TIPS combined with indwelling catheter-directed thrombolysis at the Affiliated Beijing Shijitan Hospital of Capital Medical University of China between January 2016 and December 2019,were retrospectively analyzed.Before and after TIPS,the inferior vena cava pressure(IVCP)and portal vein pressure(PVP)were measured,and the pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis portal pressure gradient(PPG,PPG=PVP-IVCP)was separately calculated.Reexamination of portal venography DSA was performed to determine the degree of PVT disappearance and whether the shunt was unobstructed.All patients were followed up for one year.Results The pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis mean PPG was(24.50±6.91)mmHg,(18.51±5.11)mmHg,and(10.17±3.97)mmHg,respectively.The post-thrombolysis mean PPG was strikingly lower than the pre-thrombolysis values,the differences were statistically significant(P＜0.001).Among the 307 patients,complete disappearance of PVT was observed in 221(72.3%),remarkable reduction of PVT in 86(27.7%),and no invalid result was seen.The patients having complete patency of the shunt flow accounted for 85.7%of the 307 patients(261/307),and the patients having partial patency of the shunt flow accounted for 14.3%of the 307 patients(46/307).Forty-two patients developed complications,and no death occurred.All patients were followed up for one year,and the main clinical symptoms were improved or completely disappeared.Among the 307 patients,an increase in thrombus volume was found in 17(5.5%)when compared to their postoperative values,which returned to the first-time postoperative level after local treatment of the thrombus via the TIPS shunt combined with catheter-directed thrombolysis.Within one year after TIPS and thrombolysis,overt hepatic encephalopathy(OHE)occurred in 54 patients(17.6%,54/307).One patient died of hepatic failure 9 months after TIPS,another patient died of cerebral hemorrhage 11 months after TIPS,and all the remaining patients were alive.Conclusion For patients with portal hypertension complicated by PVT,TIPS combined with indwelling catheter-directed thrombolysis is clinically safe and effective.The standardized,systematic management of the whole therapeutic process should be strengthened.(J Intervent Radiol,2024,32:22-27)

Objective:To evaluate the incidence, clinical significance and influencing factors on in-stent stenosis(ISS) after treatment of intracranial aneurysms by Pipeline embolization device(PED).Methods:A retrospective analysis was conducted on the clinical data of 161 patients with intracranial aneurysms treated with PED at the Department of Interventional Radiology of the First Affiliated Hospital of Zhengzhou University from April 2015 to July 2021. PED was implanted into the parent artery through the femoral artery approach after general anesthesia. The first DSA follow-up duration time and imaging data were collected, and the patients were divided into ISS group and non-ISS group accordingly. The degree of aneurysm occlusion was evaluated by O′Kelly-Marotta(OKM) grading scale. Univariate and multivariate logistic regression analysis were applied to identify the factors related to ISS.Results:A total of 179 PED were employed in 161 patients with 168 aneurysms. Eighty-eight (52.38%) aneurysms were treated by PED only, and 80 (47.62%) aneurysms by PED combined with coiling. After a median follow-up of 6 (5, 7) months, 31(18.45%) aneurysms had ISS within the PED, of which 16(9.52%) cases were with mild stenosis (<50%), 13 (7.74%) were with moderate stenosis (50%-75%), and 2(1.19%) were with severe stenosis (>75%). All patients with ISS showed no relevant clinical symptoms. One (0.60%) patient with ISS underwent balloon angioplasty. Univariate analysis showed that the stent diameter, aneurysm location, triglyceride level, the diameter of distal parent artery, and the diameter of proximal parent artery were associated to ISS. Further multivariate logistic regression analysis showed the stent diameter (OR=0.332, 95%CI 0.191-0.578, P<0.001) and triglyceride level (OR=1.641, 95%CI 1.034-2.605, P=0.036) were independent factors of ISS. Conclusions:ISS is a common benign complication after PED treatment. The current results suggest that small stent diameter and high triglyceride level are independent factors of ISS.

Objective To observe the value of 3.0T multimodal MRI for preoperative evaluation of T stage and therapeutic efficacy of neoadjuvant for rectal cancer.Methods 3.0T multimodal MRI data,including T1WI,T2WI/diffusion weighted imaging(DWI),dynamic contrast enhanced MRI(DCE-MRI)and intravoxel incoherent motion DWI(IVIM-DWI)of 150 patients with rectal cancer were retrospectively analyzed,and the value of different sequences for evaluating T stage and therapeutic efficacy of neoadjuvant for rectal cancer were assessed.Results The sensitivity,specificity and accuracy of T1WI,T2WI/DWI,DCE-MRI and IVIM-DWI for evaluating T1-T2 and T3-T4 stage rectal cancer were all significantly different(all P＜0.05).The diagnostic efficacy of DCE-MRI and IVIM-DWI were all higher than that of T1WI and T2WI/DWI(all P＜0.05).Combination evaluation of DCE-MRI and IVIM-DWI for T stage of rectal cancer had good consistency with pathological results(Kappa=0.943,P＜0.05).Significant differences of volume transfer constant(Ktrans),true diffusion coefficient(D)and apparent diffusion coefficient(ADC)were found among different T stage rectal cancers(all P＜0.05).Totally 80 patients received neoadjuvant therapy,and significant differences of Ktrans,D and ADC were noticed between patients with good(n=32)or poor efficacy(n=48)(all P＜0.05).The area under the curve(AUC)of Ktrans,D and ADC for evaluating therapeutic efficacy of neoadjuvant for rectal cancer was 0.774,0.837 and 0.758,respectively,of the combination of above three was 0.929,higher than that of single indexes(all P＜0.05).Conclusion Combination of 3.0T DCE-MRI and IVIM-DWI was helpful for preoperative evaluating T stage and therapeutic efficacy of neoadjuvant for rectal cancer.

Objective:To analyze the correlation between the posterior malleolus fracture and fixation and the rotational stability of the ankle and to explore the surgical indications for posterior malleolus fracture aiming to provide the theories for the diagnosis and treatment of disorder.Methods:Twenty fresh frozen cadaver specimens were selected. Further, the extent of the tibial insertion of the posterior inferior tibiofibular ligament (PITFL) and inferior transverse tibiofibular ligament (ITTFL) complex was dissected and measured. Based on the tibial insertion of the ligament complex, the model for the supination-external rotation degree 3 ankle fracture with a posterior malleolar fragment and syndesmosis diastasis was created. Moreover, the area threshold of the posterior tibial insertion of posterior malleolus fracture was biomechanically assessed. The difference of the antirotating ability of the ankle-stiffness between simple posterior malleolus fixation and simple syndesmotic fixation was analyzed statistically.Results:The PITFL and ITTFL were presented in all specimens with relatively broad in PITFL tibial insertion. The PITFL was attached to the posterolateral tibia. The distance between the highest point of the tibial insertion and the articular line was 45.2±5.6 mm, while the ITTFL was attached to the posterior distal tibia. The distance between the highest point of the tibial insertion and the articular line was 5.5±1.0 mm. The width of the tibial insertion of the PITFL and ITTFL complex decreased as the distance from the joint line increased. Biomechanical analysis showed that the threshold of posterior area of posterior malleolus fracture was 1/4S. The stiffnesses of posterior malleolus fixation and syndesmosis stabilization were 0.264±0.080 N·m/° and 0.164 ± 0.061 N·m/°, respectively. The percentage of stiffness restored by posterior ankle fixation was 60.9%±10.2%, which was greater than that by syndesmosis stabilization 37.5%±7.9% ( t=17.09, P<0.001) . Conclusion:The surgical technique for posterior malleolus fracture should consider restoration of the axial and rotational stability of the ankle simultaneously. Posterior malleolus fracture fixation is recommended when the syndesmosis is unstable with the area ratio of posterior tibial insertion of posterior malleolus fracture greater than or equal to 1/4. Syndesmotic fixation is proposed to restore and maintain the rotational stability of the ankle when the syndesmosis is unstable with the area ratio less than 1/4. Regardless of the area ratio, the surgical indications for stable syndesmosis depend on the impact of the posterior malleolus fracture on the axial stability of tibiotalar joint, on the involved articular surface area and on the displacement degree of posterior malleolus fragment.

Objectives:To investigate the effects of morning blood pressure on vascular endothelial function and chronic inflammatory response in the elderly.Methods:349 elderly people aged ≥60 who underwent 24-hour ambulatory blood pressure monitoring in Gaomi Municipal Hospital from April 2018 to October 2019 were selected to detect brachial artery flow mediated vasodilation (FMD) and chronic inflammatory factors [high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α) and interleukin (IL)-17] levels. According to the results of 24-hour ambulatory blood pressure monitoring, the subjects were divided into normal blood pressure group ( n=108), simple morning hypertension group ( n=114) and hypertension group ( n=127). The clinical data, 24-hour ambulatory blood pressure parameters, vascular endothelial function and inflammatory factors of the three groups were compared. The correlation between 24-hour ambulatory blood pressure parameters and FMD and inflammatory factors was analyzed by partial correlation. Results:Compared with the normal blood pressure group, the simple morning hypertension group and the hypertension group had lower FMD (all P<0.05), higher serum hsCRP and TNF-α , IL-17 levels (all P<0.05). Compared with the simple morning hypertension group, the hypertension group had lower FMD ( P<0.05), higher serum hsCRP, TNF-α and IL-17 levels (all P<0.05). After controlling for age, sex, smoking history, drinking history, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood glucose and 24 h average blood pressure, the morning systolic blood pressure was negatively correlated with FMD ( P<0.05), and positively correlated with serum hsCRP and TNF-α and IL-17 levels (all P<0.05); the morning diastolic blood pressure was negatively correlated with FMD ( P<0.05) and positively correlated with serum hsCRP and TNF-α levels (all P<0.05). Conclusions:Morning blood pressure level is closely related to vascular endothelial function and chronic inflammation level, and is independent of 24-hour average blood pressure. The increase of morning blood pressure may be an important risk factor for endothelial dysfunction and chronic inflammation in the elderly.

Objective:To propose a new classification of posterior malleolus fracture to further clarify its pathoanatomy.Methods:Twenty fresh frozen cadaver specimens of normal morphology of lower limbs were selected and dissected and the extent of the tibial insertion of posterior malleolus associated ligaments was measured. At the same time, a retrospective case series analysis was made on the clinical and CT information of 296 patients with posterior malleolus fracture treated at Tongji Hospital of Tongji University from January 2012 to July 2020 or at Karamay Central Hospital from January 2018 to July 2020. The percentage of articular involvement of the fracture, proximal displacement of the posterior malleolus fracture and extent of posterior talar subluxation were measured. A clinically practical new classification system for posterior malleolus fracture was created by correlating posterior malleolus associated ligaments with CT images of posterior malleolus fracture. The new classification included three types: type I was posterior malleolus fracture with only the tibial insertion of inferior transverse tibiofibular ligament involved; type II was posterior malleolus fracture with both the tibial insertions of inferior transverse tibiofibular ligament and posterior inferior tibiofibular ligament involved, which was divided into subtypes IIA and IIB based on the presence of articular cartilage and subchondral bone damage, compression or Die-Punch fragments; type III was posterior malleolus fracture that involved all the tibial insertions of inferior transverse tibiofibular ligament, posterior inferior tibiofibular ligament and posterior tibiotalar ligament, which was sub-classified into subtypes III A and III B according to number of fracture fragments. Anatomic characteristics of the extent of the tibial insertion of posterior malleolus associated ligament, CT imaging parameters for posterior malleolus fracture and corresponding fracture typing were determined. In addition, the new classification system for posterior malleolus fracture was compared with Haraguci classification and Mason classification.Results:Posterior malleolus associated ligaments included the posterior inferior tibiofibular ligament, inferior transverse tibiofibular ligament and posterior tibiotalar ligament from posterolateral to posteromedial tibia. The posterior inferior tibiofibular ligament was attached to the posterolateral tibia and the distance between the highest point of its tibial insertion and the joint line was (45.2±5.6)mm. The inferior transverse tibiofibular ligament was attached to the posterior distal tibia and the distance between the highest point of its tibial insertion and the joint line was (5.5±1.0)mm. The posterior tibiotalar ligament was attached to the posterior colliculus and intercollicular groove of the medial malleolus and the distance between the center of its tibial insertion and the intercollicular groove was (2.5±0.6)mm. Among 296 patients with posterior malleolus fracture, there were 36 patients with type I, 229 with type II (150 type IIA, 79 type IIB) and 31 with type III (11 type IIIA, 20 type IIIB). The percentage of articular involvement of the fracture, proximal displacement of posterior malleolus fracture and extent of posterior talar subluxation in type IIB fracture were significantly greater than those in type II A fracture [23.7(18.6, 28.8)% vs. 18.4(12.7, 21.7)%, 4.1(2.1, 6.0)mm vs. 1.9(0.2, 3.0)mm, 4.7(1.5, 6.2)mm vs. 2.3(1.1, 3.0)mm] (all P<0.01). The proximal displacement of posterior malleolus fracture and extent of posterior talar subluxation in type III fracture were significantly greater than those in type II fracture [7.2(6.0, 8.2)mm vs. 2.7(0.4, 4.0)mm, 10.1(6.0, 15.0)mm vs. 3.1(1.1, 5.0)mm] (all P<0.01). The new classification for posterior malleolus fracture combined the posterior malleolus ligament and injury mechanism of posterior malleolus fracture as compared with Haraguchi classification, which not only further detailed the classification, but also was more practical in clinic for increased the severity of injury was elevated with higher classification level. The new classification was more comprehensive as compared with Mason classification for it mainly added the type of simple-rotation-type posterior malleolus fracture (type IIA of the new classification). Conclusions:In combination with posterior malleolus associated ligaments, injury mechanism and fracture morphology, posterior malleolus fracture is divided into three types. The new classification system more comprehensively describes pathoanatomy of posterior malleolus fracture that contributes to related basic research and clinical diagnosis and treatment.

Objective:To explore the safety of cyclophosphamide combined with taxane chemotherapy in triple-negative breast cancer patients with chronic renal failure and the management strategy of complications.Methods:Data of 8 patients with triple-negative breast cancer and chronic renal failure admitted to our hospital from Jun 2016 to Dec 2019 were retrospectively analyzed.Results:Eight patients received standard cyclophosphamide combined with taxane (TC regimen) chemotherapy after operation, 5 of which received docetaxel 75 mg/m 2 + cyclophosphamide 600 mg/m 2, and 3 received albumin paclitaxel 260 mg/m 2+ cyclophosphamide 600 mg/m 2, during chemotherapy, only leukopenia, hair loss and gastrointestinal reactions occurred in grades 3 to 4, and the incidence was 25%, 25% and 12%, respectively. Four patients adjusted the dosage due to adverse reactions. One patient quit, the remaining patients successfully completed 4 cycles of chemotherapy. The average serum creatinine before chemotherapy was (498±63) μmol/L, and after chemotherapy, it was (518±61) μmol/L ( t=-2.335, P>0.05). Conclusions:Combined with chronic renal failure is not a contraindication to postoperative chemotherapy for patients with breast cancer. It is safe to choose standard TC regimen and adjust the dose of adjuvant chemotherapy for patients with triple-negative breast cancer.