Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

AIM:To investigate the effects of ginkgetin on neurological deficit and angiogenesis induced by cerebral ischemia/reperfusion(I/R)and its underlying mechanism.METHODS:Sixty SD rats were randomly allocated into three groups:sham group,I/R model group,and ginkgetin(40 mg/kg)treatment(I/R+ginkgetin)group,with twenty rats in each group.The middle cerebral artery occlusion/reperfusion(MCAO/R)rat model was employed to simulate cere-bral I/R,and ginkgetin was administered continuously for 7 days following reperfusion.The cerebral infarction volume was quantified using TTC staining.Neuronal density in the ischemic penumbra was assessed through Nissl staining and immu-nohistochemistry for neuron-specific nuclear protein(NeuN).Microvessel density and angiogenesis in the ischemic pen-umbra of each group were analyzed using CD31 labeling and BrdU/von willebrand factor(vWF)double labeling immuno-fluorescence staining.Western blot analysis was performed to determine the levels of heat shock protein 70(HSP70),vas-cular endothelial growth factor(VEGF),and hypoxia inducible factor-1α(HIF-1α)in the ischemic penumbra.RE-SULTS:Compared with the I/R model group,the cerebral infarction volume was significantly reduced in ginkgetin treat-ment group(P<0.01),the number of neurons,the microvessel density,angiogenesis and the expression levels of HIF-1α,VEGF,and HSP70 in the ischemic penumbra were significantly increased(P<0.01).CONCLUSION:Ginkgetin exhibits the potential to augment angiogenesis and facilitate neurological function recovery in MCAO rats,while concur-rently upregulating the expression of HSP70,VEGF,and HIF-1α within the ischemic penumbra.

【Objective】 To reduce the incidence of postoperative intestinal obstruction, we tried to improve surgical techniques by closing the cavity formed during radical cystectomy + ileal passage (Bricker) via laparoscopy to prevent the formation of abdominal hernia. 【Methods】 During Oct.2018 and Feb.2022, 41 patients were involved (conventional group). After standard laparoscopic radical cystectomy + pelvic lymphadenectomy, the ileum channel was established. The right medial retroperitoneum was sutured to cover the mesothelium and end of the ileum channel under open operation or endoscope. The space between the ureter and mesothelium of the ileum channel was sealed, and the end of the ileum channel and both ureters were externalized. During Feb.2022 and Dec.2022, 15 patients were involved (modified group). The right inner and outer lateral peritoneums below the ileal conduit were sutured to "bottom out" the gap between the ileal conduit and the right abdominal wall in addition to standard procedures. The recovery of intestinal function and incidence of bowel obstruction were compared between the two groups. 【Results】 In the conventional group, the intestinal function recovered within 2 to 6 days after surgery, with a median ventilation time of 3 days. Intestinal obstruction occurred in 3 patients, 2 of whom improved after conservative treatment while 1 underwent surgical exploration after ineffective conservative therapy. There were no significant differences in the time of discharge and ventilation between the two groups, but no intestinal obstruction occurred in the modified group. 【Conclusion】 Peritoneal externalization at the end of ileal passage can reduce the incidence of intra-abdominal hernia and postoperative intestinal obstruction, which is worthy of clinical application.

Pain caused by surgery is an important clinical issue that seriously affects postoperative rehabilitation and health-related quality of life. Failure to effectively manage postoperative pain not only leads to a decrease in patient quality of life, increases medical expenses, but also has a negative impact on patient recovery. Therefore, it is of great clinical significance to address the challenges of acute postoperative pain management, find effective management strategies, and improve the quality of pain management. This article summarizes the current status of acute postoperative pain management in recent years, including the mechanism of pain occurrence, pain assessment methods, drug and non drug management strategies, and predictive factors for chronic postoperative pain. It also looks forward to future research directions and application prospects.

This paper discusses the application of MRN combined with 3D printing in SNM in neurogenic bladder patients with special comorbidities. In this study, 21 cases of neurogenic bladder patients with special comorbidities involved, including 14 cases into the control group and 7 cases in the experimental group. Traditional X-ray guidance was used in the control group, while the MRN combined with 3D printing navigation template positioning was used in the experimental group. Compared with those in the control group, the X-ray fluoroscopy, number of punctures, puncture time, intraoperative adjustment and testing time were significantly decreased in the experimental group. The difference of implantable pulse generator implantation rates between the two groups was statistically significant.

Enhanced recovery after surgery (ERAS) is mainly based on evidence-based medicine to implement a series of measures to optimize perioperative management, reduce patients′ physiological and psychological trauma stress during perioperative period, reduce patients′ functional damage and promote patients′ functional recovery, so as to achieve rapid rehabilitation. ERAS has been widely used in clinic and achieved good clinical results. However, it still faces a series of problems that need further research to clarify the clinical path of ERAS required by different patients and different surgical methods. In particular, it is necessary to strengthen the research on risk factors of ERAS, minimally invasive surgery, goal-directed fluid therapy, anesthesia and postoperative pain management technology, pre rehabilitation and postoperative rehabilitation technology, and implement ERAS guided by the best outcome in the perioperative period.

It is necessary to use objective and accurate methods to assess the changes of the consciousness of patients emergencing from general anesthesia. In this way, adverse medications during the waking period can be avoided, and it can ensure the stable and safe recovery of consciousness of the patients, quickly remove the adverse factors affecting the patients, and strive to reduce the occurrence of complications during the waking period. This article briefly reviews the research progress of bispectral index and other common clinical anesthesia depth monitoring techniques used to assess the changes of consciousness of patients awakening from general anesthesia, and explores the regular pattern of recovery of consciousness in patients awakening from general anesthesia, in order to reduce complications in the recovery period .

Gastric schwannoma is a tumor originating from mesenchymal tissue. The clinical incidence is relatively rare, accounting for 6.3% of all gastric stromal tumors. The tumor is more likely to occur in the body of the stomach and usually originates from the gastric submucosal nerve. Most gastric schwannomas do not have any clinical symptoms. Imaging examination can play a diagnostic role, but the diagnosis still requires pathological examination, especially S-100 protein which is the gold standard for the diagnosis of gastric schwannomas. Gastric schwannoma usually needs to be distinguished from gastrointestinal stromal tumors and gastrointestinal autonomic nerve tumors. In terms of treatment, complete surgical resection is the first choice.

Objective: To investigate the clinical efficacy of spinal endoscopic surgery for lumbar posterior ring apophysis separation (PRAS) via percutaneous transforaminal approach. Methods: A retrospective case series study was conducted to analyze the clinical data of 32 patients with lumbar PRAS admitted to the First Affiliated Hospital of Fujian Medical University from September 2016 to March 2018. There were 20 males and 12 females, aged 20-47 years [(33.7 ± 6.6)years]. All patients had single-segment lesions. The injured segments were at L_3/4 in seven patients, L_4/5 in 14 patients, L₅/S₁ in 11 patients. All patients were treated with spinal endoscopic surgery via percutaneous transforaminal approach. The incision length, operation time, intraoperative blood loss, intraoperative fluoroscopy times of C-arm X-ray machine and operational complications were recorded. At 24 hours, 3 months and 12 months after operation, the efficacy was evaluated by visual analogue score (VAS), Oswestry dysfunction index (ODI) and modified MacNab criteria. Results: All patients were followed up for 12-30 months, with an average of 15.5 months. The incision length was 7-9.5 mm [(8.0±0.9)mm], the average operation time was 60-155 minutes [(80.5±13.2) minutes], the average intraoperative blood loss was 5-25 ml [(10.6±5.7)ml] and the average number of fluoroscopy was 5-25 times [(9.4±3.4) times]. The patients were permitted to move wearing hard waist 8-12 hours after operation and returned to normal work and life 6 weeks after operation. Postoperative dysesthesia was noted in one patient, who recovered after neurotrophy and physiotherapy after one week. There were no complications such as open surgery conversion, intervertebral space infection, nerve root injury and dural sac laceration. The VAS and ODI at 24 hours, 3 months and 12 months after operation [low back pain VAS: (3.4±1.5)point, (1.8±1.1)points, (1.7±0.9)points; leg pain VAS: (1.8±1.0)points, (1.6±0.8)points, (1.4±0.6)points; ODI: (26.8±9.7)%, (13.9±4.3)%, (12.8±2.8)%] were significantly improved compared with those before operation [ back pain VAS: (7.3±2.1)points, leg pain VAS: (7.9±2.7)points; ODI: (56.2±15.6)%] (P<0.05). According to the modified MacNab criteria, the results were excellent in 25 patients, good in five patients, and fair in two patients, with the excellent and good rate of 94%. Conclusion Spinal endoscopic surgery for lumbar PRAS via percutaneous transforaminal approach is an effective method with advantages of small incision, less complications, effective pain relief and fast functional recovery.

OBJECTIVE:To compare therapeutic efficacy and safety of indapamide separately combined with benazepril,irbe-sartan or amlodipine for grade 2 essential hypertension(EH). METHODS:A total of 150 patients with grade 2 EH were randomly divided into benazepril group(50 cases),irbesartan group(50 cases)and amlodipine group(50 cases). 3 groups were given Indap-amide tablet 2.5 mg orally,once a day. Benazepril group was additionally given Benazepril hydrochloride tablet 10 mg orally,once a day;irbesartan group was additionally given Irbesartan tablet 150 mg orally,once a day;amlodipine group was additionally giv-en Amlodipine tablet 5 mg orally,once a day. 3 groups were treated for 12 weeks. The levels of systolic pressure,diastolic pres-sure,heart rate,total cholesterol(TC),three triacylglycerol(TG)and serum potassium as well as the occurrence of ADR were ob-served in 3 groups before and after treatment. RESULTS:The total response rate of berazopril group,irbesartar group and a mloelip-ire group had no significant difference(90.0% vs. 88.0% vs. 92.0%,P>0.05). There were no statistical significances in the levels of systolic pressure,diastolic pressure,heart rate,TC,TG and serum potassium among 3 groups before treatment(P>0.05). Af-ter treatment,systolic pressure and diastolic pressure of 3 groups were significantly lower than before,with statistical significance (P<0.01);but there was no statistical significance among 3 groups(P>0.05). There were no statistical significance in heart rate, TC,TG of 3 groups before and after treatment and the level of serum potassium in benazepril group and irbesartan group (P>0.05). After treatment,the level of serum potassium in amlodipine group was significantly lower than before,with statistical signifi-cance (P<0.05). The incidence of ADR in irbesartan group was significantly lower than benazepril group and amlodipine group, with statistical significance (P<0.05);but there was no statistical significance between benazepril group and amlodipine group (P>0.05). CONCLUSIONS:The indapamide separately combined with benazepril,irbesartan or amlodipine have similar therapeu-tic efficacy for grade 2 EH,but the safety of irbesartan is better than those of benazepril and amlodipine.