Objective To verify the safety and effectiveness of a new percutaneous controllable curved plasma radiofrequency instrument for nucleus pulposus ablation. Methods A new percutaneous controllable curved plasma radiofrequency instrument were designed (controllable curved group), and its ablation effect was compared with the currently used straight head non-bendable plasma ablation instrument (non-bendable group) on gross specimens. The ablation instrument was placed through the right intervertebral foramen, and continuous ablation on the same intervertebral disc was conducted for three times. The ablation range and trajectory were recorded, and the temperature changes in the front, back, left, and right of the ablation center during and 15 seconds after ablation were monitored by the inserted temperature probe. Results There were no difference in temperature changes in the front, back, right regions of the ablation center during and 15 seconds after ablation between the two groups. The temperature changes in the left region of the ablation center both during and 15 seconds after 3rd ablation were larger than those in the non-bendable group (P＜0.01). Compared with the non-bendable group, the controllable curved group achieved angle control and larger single ablation area (2.282 5 mm² vs 1.135 8 mm², P＜0.000 1). Conclusions This new percutaneous controllable curved plasma ablation instrument can achieve angle control and ablation on the side opposite to the puncture site, increase ablation volume, and is safe.

Objective To explore the risk factors that may cause recurrent retinal detachment in rhegmatogenous retinal detachment(RRD)patients after surgery.Methods A total of 403 patients(403 eyes)with RRD diagnosed in the Department of Ophthalmology of the First Affiliated Hospital of Soochow University from October 2020 to April 2022 were included in this study.Among them,35 patients underwent the scleral buckling,79 patients underwent the pars plana vit-rectomy(PPV)+intravitreal gas tamponade,222 patients underwent the PPV+intravitreal silicone oil tamponade,and 67 patients underwent the PPV+vitreous silicone oil tamponade+silicone oil removal.The postoperative follow-up lasted for at least 3 months.Risk factors affecting one-time retinal reattachment after RRD surgery were analyzed by univariate and multivariate Logistic analyses,and Logistic regression was applied to construct a risk prediction model.Results Among the 403 eyes with RRD,369 eyes had retinal reattachment on the first try,and 34 eyes did not,with a one-time reat-tachment rate of 91.6％.The univariate analysis showed that the differences in axial length(AL),surgical approach,loca-tion of the tear,and size of the tear between patients with one-time retinal reattachment and those without reattachment were statistically significant(all P＜0.05).From the regression equation,it was found that the risk of non-reattachment af-ter RRD surgery of patients with an AL ≥ 26 mm was 4.248 times higher than those with an AL＜26 mm(P＜0.05).The multivariate Logistic regression analysis showed that AL,location of the tear,size of the tear,and surgical approach were risk factors for non-reattachment after RRD surgery(all P＜0.05).The Hosmer-Lemeshow test yielded P=0.165.The re-sults of the receiver operating characteristic curve analysis showed that the area under the curve to predict whether retinal re-detachment occurs after RRD surgery was 0.892(95％CI:0.832-0.953),and the sensitivity and specificity were 79.4％and 87.3％,respectively(P＜0.05).Conclusion AL is an independent risk factor for retinal re-detachment after RRD surgery.The prediction model constructed based on AL,location of the tear,size of the tear,and the surgical method can accurately predict whether retinal detachment will occur after RRD surgery.

Objective To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma(HCC)cell proliferation and migration.Methods HCC cell lines HepG2 and Huh7 treated with calenduloside E were examined for changes in cell viability using CCK-8 assay and expressions of GPX4,SLC7A11,LC3,P62 and phosphorylation of Akt/mTOR using Western blotting.The effects LY294002 and Rapamycin(the inhibitor and activator of autophagy,respectively)on proliferation and migration of calenduloside E-treated HCC cells were evaluated using EdU and Transwell assays.The TCGA database was used to explore the expression levels of GPX4 and SLC7A11 in HCC and normal liver tissues and their correlation with the patients'survival outcomes.GPX4 and SLC7A11 expressions were also detected in HCC cells and normal hepatocytes using RT-qPCR and Western blotting.Results Calenduloside E obviously inhibited the viability of HCC cells.GPX4 and SLC7A11 were highly expressed in HCC tissues and cell lines,and their expression levels were negatively correlated with the patients'survival.In HCC cell lines,calenduloside E significantly inhibited the expressions of GPX4 and SLC7A11 proteins,activated the Akt-mTOR pathway,and enhanced the expression of LC3 II.The inhibitory effect of calenduloside E on GPX4 and SLC7A11 expressions was significantly enhanced by rapamycin but attenuated by LY294002.Inhibiting the autophagy pathway obviously diminished the inhibitory effect of calenduloside E on proliferation and migration of HCC cells,while activating this pathway produced the opposite effect.Conclusion Calenduside E inhibits the proliferation and migration of HCC cells by down-regulating GPX4 and SLC7A11 expression via the autophagy pathway.

Objective To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma(HCC)cell proliferation and migration.Methods HCC cell lines HepG2 and Huh7 treated with calenduloside E were examined for changes in cell viability using CCK-8 assay and expressions of GPX4,SLC7A11,LC3,P62 and phosphorylation of Akt/mTOR using Western blotting.The effects LY294002 and Rapamycin(the inhibitor and activator of autophagy,respectively)on proliferation and migration of calenduloside E-treated HCC cells were evaluated using EdU and Transwell assays.The TCGA database was used to explore the expression levels of GPX4 and SLC7A11 in HCC and normal liver tissues and their correlation with the patients'survival outcomes.GPX4 and SLC7A11 expressions were also detected in HCC cells and normal hepatocytes using RT-qPCR and Western blotting.Results Calenduloside E obviously inhibited the viability of HCC cells.GPX4 and SLC7A11 were highly expressed in HCC tissues and cell lines,and their expression levels were negatively correlated with the patients'survival.In HCC cell lines,calenduloside E significantly inhibited the expressions of GPX4 and SLC7A11 proteins,activated the Akt-mTOR pathway,and enhanced the expression of LC3 II.The inhibitory effect of calenduloside E on GPX4 and SLC7A11 expressions was significantly enhanced by rapamycin but attenuated by LY294002.Inhibiting the autophagy pathway obviously diminished the inhibitory effect of calenduloside E on proliferation and migration of HCC cells,while activating this pathway produced the opposite effect.Conclusion Calenduside E inhibits the proliferation and migration of HCC cells by down-regulating GPX4 and SLC7A11 expression via the autophagy pathway.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Objective:To investigate the efficacy of continuous intravenous injection of hyaluronidase (HAase) combined with urokinase (UK) in the treatment of ischemia of hyaluronic acid (HA) arterial embolized skin flap.Methods:(1)Establish an animal model of superficial abdominal artery embolization with HA: 24 SD rats were used to make a square island flap (2 cm×2 cm, the width of the pedicle is 2 mm) on the left and right sides of the abdominal white line with superficial epigastric artery as feeding artery. The left and right flaps of rats were used as experimental group and control group. After the preparation of the experimental skin flap, HA 10 μl was injected into the superficial abdominal artery, while the self-control flap was only made and the vessels were peeled off without embolization.(2)The rats were randomly divided into A, B, C and D groups by drawing lots with 6 rats in each group, After the successful establishment of embolic animal model of 45 min, HAase(2 000 IU/kg)+ UK(50 000 IU/kg), HAase(2 000 IU/kg), UK(50 000 IU/kg) and normal saline were continuously infused through caudal vein with microinjection pump. The volume of solution in each group was 6 ml in 12 minutes. The general condition of rats and the skin color, edema, congestion and skin necrosis in the operation area of rats were observed, which were photographed and compared immediately, and at 3 days, 5 days and 7 days after embolization. The images were analyzed by Photoshop software, and the percentage of survival area of the flap after operation 7 days, was measured by pixel method. The percentage of survival area was compared by single factor analysis of variance (ANOVA) and head-to-head comparison by LSD- t test. Results:Immediately after operation, all the flaps in the four groups were pale and there was no obvious swelling. All the flaps showed different degrees of swelling within 3 days after operation, and the swelling basically disappeared within 3-5 days after operation, and gradually changed from dark red ecchymosis to dark purple or black. Seven days after operation, the necrotic area flap gradually hardened and its boundary was obvious. The skin flaps of the 4 groups showed different degrees of necrosis. The postoperative reaction of the flap was the slightest in group A, the performance of group B and C was similar, which were both between group A and group D, and there was the heaviest postoperative reaction in group D. At 7 days after operation, the percentage of survival area of flaps in groups A, B, C and D was 90.30%±5.95%, 52.63%±6.90%, 51.14%±5.95% and 7.70%±2.18%, respectively. The percentage of survival area of skin flap in group A was significantly higher than that in groups B, C and D (analysis of ANOVA: P<0.01; LSD- t test: P<0.01). Conclusions:Continuous intravenous infusion of HAase combined with UK can effectively alleviate the flap ischemia caused by HA artery embolism, increase tissue perfusion and increase the survival area of the flap.

Objective:To investigate the efficacy of continuous intravenous injection of hyaluronidase (HAase) combined with urokinase (UK) in the treatment of ischemia of hyaluronic acid (HA) arterial embolized skin flap.Methods:(1)Establish an animal model of superficial abdominal artery embolization with HA: 24 SD rats were used to make a square island flap (2 cm×2 cm, the width of the pedicle is 2 mm) on the left and right sides of the abdominal white line with superficial epigastric artery as feeding artery. The left and right flaps of rats were used as experimental group and control group. After the preparation of the experimental skin flap, HA 10 μl was injected into the superficial abdominal artery, while the self-control flap was only made and the vessels were peeled off without embolization.(2)The rats were randomly divided into A, B, C and D groups by drawing lots with 6 rats in each group, After the successful establishment of embolic animal model of 45 min, HAase(2 000 IU/kg)+ UK(50 000 IU/kg), HAase(2 000 IU/kg), UK(50 000 IU/kg) and normal saline were continuously infused through caudal vein with microinjection pump. The volume of solution in each group was 6 ml in 12 minutes. The general condition of rats and the skin color, edema, congestion and skin necrosis in the operation area of rats were observed, which were photographed and compared immediately, and at 3 days, 5 days and 7 days after embolization. The images were analyzed by Photoshop software, and the percentage of survival area of the flap after operation 7 days, was measured by pixel method. The percentage of survival area was compared by single factor analysis of variance (ANOVA) and head-to-head comparison by LSD- t test. Results:Immediately after operation, all the flaps in the four groups were pale and there was no obvious swelling. All the flaps showed different degrees of swelling within 3 days after operation, and the swelling basically disappeared within 3-5 days after operation, and gradually changed from dark red ecchymosis to dark purple or black. Seven days after operation, the necrotic area flap gradually hardened and its boundary was obvious. The skin flaps of the 4 groups showed different degrees of necrosis. The postoperative reaction of the flap was the slightest in group A, the performance of group B and C was similar, which were both between group A and group D, and there was the heaviest postoperative reaction in group D. At 7 days after operation, the percentage of survival area of flaps in groups A, B, C and D was 90.30%±5.95%, 52.63%±6.90%, 51.14%±5.95% and 7.70%±2.18%, respectively. The percentage of survival area of skin flap in group A was significantly higher than that in groups B, C and D (analysis of ANOVA: P<0.01; LSD- t test: P<0.01). Conclusions:Continuous intravenous infusion of HAase combined with UK can effectively alleviate the flap ischemia caused by HA artery embolism, increase tissue perfusion and increase the survival area of the flap.

This paper aims to explore the main points of diagnosis， treatment and misdiagnosis of conversion disorder characterized by paroxysmal abdominal pain. The general hospitals had a high misdiagnose rate and no effective symptomatic treatment for conversion disorder patients with physical discomfort as main symptoms， which leading to heavy physical and mental burden of patients and waste of medical resources， so this paper retrospectively analyzed the etiology， diagnostic process， treatment and therapeutic effect of a case of conversion disorder with paroxysmal abdominal pain as the main symptom. Case analysis showed that the physical discomfort as chief complain of conversion disorder patients affected the rate of early correct diagnosis and treatment， so clinicians' ability of diagnosis and differential diagnosis of conversion disorder needs to be strengthened. At the same time， cognitive behavioral therapy （CBT） is effective in the clinical treatment and recurrence prevention of conversion disorder.

Objective:To explore the relationship among the supratrochlear and supraorbital neurovascular bundles and the corrugator muscle, in order to provide anatomical basis for eyebrow operations.Methods:From July to October 2019, the upper eyelids and forehead of 10 adult skull specimens (20 sides) were dissected layer by layer in the anatomy laboratory of Weifang Medical College. The line of bilateral inner canthus was taken as the X-axis and the facial midline as the Y-axis to establish the coordinate system. The coordinate parameters of supratrochlear nerve, supratrochlear artery, medial branch of supraorbital nerve, lateral branch of supraorbital nerve and supraorbital artery were measured to obtain the range of its trajectory, and their level and their adjacent relationship with the corrugator muscle were observed.Results:The corrugator muscle started from the upper part of the nasal process of the frontal bone near the medial margin of the orbit and was (4.32±0.98) mm from the midline. The base of the corrugator muscle start was (9.91±1.41) mm wide. The corrugator muscle run obliquely upward, through orbicularis oculi muscle and frontal muscle, and stopped at subcutaneous of the outer 1/3 of eyebrow. The trapezoid area was composed of the line of 15 mm above the inner canthus line, (16.58±1.70) mm and (16.17±1.42) mm from the facial midline as the lower base and the line of 30 mm above the inner canthus line, (13.74±1.54) mm and (14.21±2.42) mm from the facial midline, which was the dangerous area for the supratrochlear neurovascular bundles walking in corrugator muscle. The trapezoid area was composed of the line of 22.5 mm above the inner canthus line, (26.03±1.55) mm and (28.11±2.46) mm from the facial midline as the lower base and the line of 40 mm above the inner canthus line, (31.23±3.19) mm and (38.20±2.94) mm from the facial midline, which was the dangerous area for the supraorbital neurovascular bundles.Conclusions:Familiar with the relationship among the supratrochlear and supraorbital neurovascular bundle and the corrugator muscle can avoid dangerous areas and reduce superficial and deep neurovascular injury during operation.

Objective:To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China.Methods:Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio ( HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results:Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion:Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.