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.

To investigate the clinical effect of electroacupuncture (EA) in preventing chemotherapy-induced peripheral neuropathy (CIPN).

To investigate the clinical efficacy of heat-sensitive moxibustion combined with intrapleural perfusion of cisplatin in comparison with simple intrapleural perfusion of cisplatin on malignant pleural effusion (MPE).

To observe the efficacy and safety of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with malignant tumors.

Objective: To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). Methods: This was a prospective randomized controlled study. Patients diagnosed with DME in the Ophthalmology Department of Beijing Hospital were enrolled from January 2020 to December 2022. Patients were randomized in a ratio of 1∶1 using a table of random numbers into the ranibizumab monotherapy group and the SMPL combined with ranibizumab therapy group. We compared the changes of best-corrected visual acuity, central macular thickness measured by optical coherence tomography and optical coherence tomography angiography parameters, including the vessel density of the superficial and deep capillary plexus (DCP), foveal avascular zone size and peripapillary vessel density, at baseline, 6 and 12 months after the treatment. After 12 months of follow-up, fundus fluorescein angiography results, adverse events, and the number of injections or laser therapies were recorded. The Fisher's exact test and group t-test were used for statistical analysis. Results: Seventy-two patients (72 eyes) were enrolled, with a mean age of (61.1±8.2) years. Patients in the combination therapy group included 19 males and 17 females, while patients in the ranibizumab monotherapy group were 17 males and 19 females. There was no statistically significant difference in baseline characteristics between the two groups (P>0.05). A significant improvement in best-corrected visual acuity was shown in both groups at 6 and 12 months [(58.5±12.9) and (58.2±12.2) ETDRS letters in the combination therapy group, and (63.3±13.1) and (63.8±12.5) ETDRS letters in the ranibizumab monotherapy group]. A significant reduction in central macular thickness was shown in both groups at 6 and 12 months [(451.0±185.5) and (380.4±159.3)μm in the combination therapy group, and (387.5±135.5) and (372.8±146.1)μm in the ranibizumab monotherapy group]. However, there was no significant difference between groups at each timepoint (all P>0.05). At 12 months, the vessel density of the superficial capillary plexus showed no statistical difference compared to the baseline value in each group or between groups (42.6%±5.9% in the ranibizumab monotherapy group and 42.2%±5.5% in the combination therapy group, P>0.05). The vessel density of the DCP in the combination therapy group significantly increased to 47.5%±5.6% at 12 months, significantly different from that in the ranibizumab group (43.4%±5.1%; P<0.05). The foveal avascular zone size in the ranibizumab monotherapy group reduced to (0.32±0.13) mm2, significantly different from that in the combination therapy group [(0.34±0.16) mm2] at 12 months (P<0.05). Patients in the ranibizumab monotherapy group received (7.3±2.5) intravitreal injections, while patients in the combination therapy group received 3 injections. No unfavorable outcomes on fundus fluorescein angiography or systemic or topical severe adverse events were observed during the follow-up. Conclusions: The SMPL combined with intravitreal ranibizumab injections was effective and safe in treating DME patients. The combination treatment significantly reduced the number of injections and improved the vessel density of the DCP and macular ischemia, compared to the ranibizumab monotherapy.

To compare the clinical effect of intradermal needling and acupuncture in prevention and treatment of leukopenia after chemotherapy with spleen-kidney deficiency.

To compare the clinical efficacy of heat-sensitive moxibustion combined with tropisetron hydrochloride and tropisetron hydrochloride alone in the treatment of chemotherapy-induced nausea and vomiting (CINV).

To observe the clinical efficacy and safety of fire dragon cupping in prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in breast cancer.

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).

Objective To investigate the effect of cisplatin (DDP) on the expression of programmed death 1 ligand 1 (PD-L1) in human lung adenocarcinoma A549 cells and its possible mechanism. Methods Human lung adenocarcinoma A549 cells were cultured in vitro and treated with (0, 0.5, 1, 2, 4, 8) mg/L of DDP for 24, 36, 48 hours. CCK-8 assay was used to detect the cell proliferation inhibition rate and the half maximal inhibitory concentration (IC50) was calculated. The optimal inhibition time of 48 hours and its IC50 were selected for subsequent experiments. A549 cells were then randomized into four groups: blank control group, group with DDP (IC50), group with 20 μmol/L of mitogen-activated protein kinase kinase inhibitor PD98059, and group with DDP (IC50) combined with 20 μmol/L of PD98059. The cells were cultured for 48 hours. The expression of ERK and p-ERK were detected by Western blotting, and PD-L1 expression was detected by flow cytometry. Results Compared with that in the control group, the expression of PD-L1 in A549 cells treated with DDP was up-regulated in a dose-dependent manner. The optimal time was 48 hours and the IC50 was 3.586 mg/L. Also compared with that in the control group, the expression of p-ERK and PD-L1 in the DDP treatment group increased, and the expression of p-ERK in the group with PD98059 decreased. The expressions of p-ERK and PD-L1 in the group with DDP combined with PD98059 were lower than those in the group with DDP, but higher than those in the group with PD98059. Conclusion DDP up-regulates the expression of PD-L1 in A549 cells by activating the ERK signaling pathway.

To compare the effects of medical ozone oil and urea ointment for prevention and treatment of hand-foot skin reaction (HFSR) caused by sorafenib in patients with hepatocellular carcinoma (HCC).

Objective: To compare the accuracy of abdominal enhanced CT and endoscopic ultrasound in the staging of gastric cancer after neoadjuvant chemotherapy (yc stage). Methods: Clinic data of 86 locally advanced gastric cancer patients admitted in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute from April 2015 to November 2017 were analyzed retrospectively. Totally 86 patients completed both abdominal enhanced CT and endoscopic ultrasound after neoadjuvant chemotherapy. There were 60 males and 26 females, aged (57.8±9.7) years (range: 32 to 76 years). The diagnostic accuracy of abdominal enhanced CT and endoscopic ultrasound for yc stage were calculated by the area under the multiclass receiver operation characteristic curve (M-AUC), retrospectively. McNemar test was used to compared the diagnostic sensitivity. Results: The M-AUC of ycT stage evaluated by abdominal enhanced CT (CT-ycT stage) and by endoscopic ultrasound (EUS-ycT stage) was 0.614 and 0.704, respectively. For middle and lower gastric cancer, the M-AUC of CT-ycT stage was 0.599 and 0.613, respectively, while EUS-ycT stage was 0.558 and 0.709, respectively. For tumor in the lesser and non-lesser curvature, the M-AUC of CT-ycT stage was 0.630 and 0.607, respectively, while EUS-ycT stage was 0.616 and 0.749, respectively. For patients in CT-ycT1-CT-ycT4, there was no statistically significant difference in the sensitivity between CT-ycT stage and EUS-ycT stage (2/18, 2/15, 52.8%(19/36), 8/13 vs. 0, 4/15, 55.6%(20/36), 7/13; χ(2)=2.00, P=0.157; χ(2)=2.00, P=0.157; χ(2)=0.08, P=0.782; χ(2)=0.33, P=0.564). The M-AUC of ycN stage evaluated by abdominal enhanced CT (CT-ycN stage) was 0.654, while ycN stage evaluated by endoscopic ultrasound (EUS-ycN stage) was 0.533. For patients in CT-ycN0, there was statistically significant difference in the sensitivity between CT-ycN stage and EUS-ycN stage (12.7%(7/55) vs. 5.5%(3/55); χ(2)=4.00, P=0.046). For patients in CT-ycN1, N2, and N3, there was no statistically significant difference in the sensitivity between CT-ycN stage and EUS-ycN stage (2/19, 1/10, 0 vs. 1/19, 1/10, 0; χ(2)=1.00, P=0.317; the other P cannot be estimated). Conclusions: There was no significant difference between the diagnostic efficacy of abdominal enhanced CT and endoscopic ultrasound for yc stage of gastric cancer. Considering the invasiveness of ultrasound gastroscopy, it should not be recommend for patients after neoadjuvant chemotherapy routinely.

To observe the effect of ginger-partitioned moxibustion intervention on gastrointestinal reaction, the quality of life, the counts of blood platelet (PLT) and white blood cells (WBC) after chemotherapy in lung cancer patients.

Objective: To investigate the effects of targeted artery perfusion of verapamil and chemotherapy drugs on advanced non-small cell lung cancer (NSCLC). Methods: Sixty patients with advanced NSCLC who were admitted to the Central Hospital of Zhumadian from April 2016 to April 2018 were selected as the research subjects. They were divided into the observation group (26 cases) and the control group (34 cases) according to the treatment method. Patients in the observation group were treated with targeted artery perfusion of verapamil and chemotherapy drugs while the control group were treated with target artery perfusion of chemotherapy drugs alone.Both groups were treated continuously for more than 2 months. The short-term curative effect, adverse reactions, changes in immune function, levels of serum tumor markers and Karnofsky Performance Scale (KPS) scores before and after treatment as well as the prognosis were compared between the two groups. Results: The response rate and control rate in the observation group were 80.8% and 96.2%, higher than 55.9% and 76.5% in the control group (P<0.05). After treatment, CD4(+) levels and CD4(+) /CD8(+) in the observation group were (25.43±2.76)% and (0.88±0.11), lower than (27.56±2.79)% and (0.95±0.13) in the control group (P<0.05). After treatment, serum levels of CEA and CA50 in the observation group were (11.57±2.32)ng/ml and (16.62±3.28)U/ml, also lower than (15.87±2.66)ng/ml and (20.31±3.42)U/ml in the control group (P<0.05). There was no significant difference in adverse reactions between the two groups (P>0.05). After treatment, KPS score of the observation group was (81.44±2.76) points, higher than (79.62±2.38) points of the control group (P<0.05). The median survival time and progression-free median survival time of the observation group were 16.0 months and 7.5 months, respectively, significantly better than 10.0 months and 5.0 months of the control group (P<0.05). Conclusions: The treatment with target arterial perfusion of verapamil and chemotherapy drugs for advanced NSCLC can effectively improve the short-term curative effect, reduce serum levels of tumor markers, improve life quality and prolong the survival time. However, it has a certain inhibitory effect on the patient's immune function.

Objective: To evaluate the effect of oral nutritional supplementation (ONS) on the nutritional status and quality of life in patients with colorectal cancer and postoperative adjuvant chemotherapy. Methods: This study was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-13003798). A multi-center randomized controlled trial was conducted. Colorectal cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy, and had nutritional risk (nutrition risk screening 2002 score ≥3) when discharge from hospital in six hospitals (Beijing Hospital, Peking University Third Hospital, Guangzhou Nanfang Hospital, Shanghai Xinhua Hospital, Shanghai Ruijin Hospital, and Shanghai The Sixth People's Hospital) from June 2013 to August 2015 were prospectively enrolled. These patients were randomly divided into the ONS group and control group. Patients in the ONS group received dietary guidance and oral nutritional supplements (2092 kJ/day, whole protein enteral nutrition) for 90 days after discharge from hospital, while patients in the control group only received dietary guidance. Anthropometric measurements (body weight, body mass index [BMI], upper arm circumference, gripping power of the dominant hand, triceps skin fold), nutrition-related laboratory tests (hemoglobin, albumin, prealbumin, total cholesterol, triglyceride), gastrointestinal function scores and quality of life (evaluated by EuroQol five dimensions questionnaire) were collected and compared at baseline (at discharge), and at 30-day, 60-day and 90-day after discharge. Results: A total of 90 patients were included into this multi-center study, of whom 5 patients dropped out, 43 patients were assigned to the ONS group and 42 patients to the control group. Compared with baseline, the body weight of patients in the ONS group increased by (1.523±0.525) kg at 60-day and (1.967±0.661) kg at 90-day, which were significantly higher than those of patients in the control group [60-day: (-0.325±0.518) kg, P=0.015; 90-day: (-0.224±0.705) kg, P=0.027, respectively]. A similar pattern was observed for BMI, the ONS group increased by (0.552±0.203) kg/m(2) at 60-day and (0.765±0.205) kg/m(2) at 90-day, which were significantly higher than those of patients in control group [60-day: (-0.067±0.202) kg/m(2), P=0.034; 90-day: (0.022±0.210) kg/m(2), P=0.013]. No significant differences of other anthropometric measurements and nutrition-related laboratory tests were found between the two groups (all P>0.05). Furthermore, there were no significant differences of improvement in gastrointestinal function and quality of life between two groups (all P>0.05). Conclusion: Oral nutritional supplements can improve the body weight and BMI of colorectal cancer patients with nutritional risk receiving postoperative adjuvant chemotherapy, though it does not improve the quality of life.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has a unique effect on the prevention and treatment of peritoneal metastasis from malignancies. Recently, the first prospective, multicenter, randomized controlled clinical trial of HIPEC to prevent the development of peritoneal metastasis after curative surgery for patients with locally advanced colon cancer was published in the "Lancet Gastroenterol Hepatol" (COLOPEC). Regrettably, no significant difference was observed in 18-month peritoneal metastasis-free survival between postoperative adjuvant HIPEC and standard systemic chemotherapy for patients with T4 stage or perforated colon cancer. However, we wonder whether we might achieve better outcomes by further optimizing the following issues: (1) We propose that the inclusion criteria for that trial may not be entirely reasonable, which included pT4N0-2M0 and perforation. Additionally, we found that 91% of patients underwent HIPEC 5-8 weeks after primary tumor resection. (2) The imbalance in starting time of postoperative systemic chemotherapy between the two groups may have a negative impact.(3) Nine patients with peritoneal metastasis preceding HIPEC might weaken the potential efficacy of HIPEC. (4) We wonder whether HIPEC using high-dese oxaliplatin (460 mg/m(2)) perfusing 30 minutes for one cycle is the optimal regimen. Therefore, we are planning to conduct a randomized controlled trial (HIPEC-06) in accordcance with the characteristics of Chinese patients, to explore the clinical efficacy of curative surgery combined with HIPEC in the treatment of cT4 colorectal cancer.

Objective: To evaluate the efficacy and safety of apatinib combined with chemotherapy in the first-line treatment of advanced non-small cell lung cancer (NSCLC) with negative driving genes. Methods: From January 2016 to March 2018, 62 advanced NSCLC patients with negative driving genes diagnosed at Xuzhou Cancer Hospital were randomly divided into study group (30 cases) and control group (32 cases), respectively. The patients in the study group were treated with standard first-line chemotherapy combined with apatinib, while those in control group were treated with chemotherapy alone. Results: The disease control rate (DCR) and objective remission rate (ORR) in the study group were 60.0% and 16.7%, respectively, higher than 46.9% and 9.3% in the control group, but without statistical difference (P>0.05). The median progression-free survival (PFS) of study group and control group were 6.4 months and 4.9 months, respectively (P=0.004), and the median overall survival (OS) were 11.3 months and 9.2 months, respectively (P=0.006). Multivariate survival analysis indicated that treatment regimen (P=0.001) was the independent prognostic factor of PFS, and PS score (P=0.002), clinical stage (P=0.02) and treatment regimen (P<0.001) were the independent prognostic factors of OS. After treatment, the incidence of hypertension and hand-foot syndrome in the study group were 46.7% and 53.3%, respectively, significantly higher than 3.3% and 0 in the control group, respectively (P<0.05). The incidence of grade 3-4 adverse drug reactions (ADRs) in the study group was 26.7% (8/30), mainly including hypertension, hand-foot syndrome and bone marrow suppression. The incidence of grade 3-4 ADRs in the control group was 15.6% (5/32), all of which were bone marrow suppression, without significant difference (P=0.286). There was no difference in serum levels of VEGF and CEA between the two groups before treatment. After treatment, the serum level of VEGF in the study group was (169.3±10.1) pg/ml, lower than (211.8±16.7) pg/ml of the control group (P<0.05). Conclusion: Apatinib combined with first-line chemotherapy for advanced NSCLC patients with negative driving genes is safe and beneficial for survival. This therapeutic strategy can significantly prolong the PFS and OS, and further improvement and application can be considered as a choice in the clinical treatment.

Objective: There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib,a novel multitargeted receptor tyrosine kinase inhibitor, has previously shown antitumor activity in phase Ⅱ studies of patients with advanced MTC. This study was to evaluate the efficacy and the safety of vandetanib on advanced MTC. Methods: This study was an open, international multi-center phase Ⅲ clinical trial and the study number was NCT01298323. The single-center study was a sub-group analysis of the international study, which was conducted on 9 pathologically confirmed advanced MTC patients by Cancer Hospital Chinese Academy of Medical Sciences between March 2012 and October 2017. Vandetanib (300 mg) was orally administered daily till death or withdrawal. The efficacy was evaluated according to RECIST criteria and the adverse events were evaluated according to NCI criteria. Results: The objective response rate was 3/9,and the disease control rate was 4/9. The median progression-free survival was 44 months. All patients who had the elevated levels of calcitonin (CTN) and carcino-embryonic antigen (CEA) before treatment began to show the decreases in the level of CTN and CEA after 3 months and later showed again the increases in the levels of both tumor markers with tumor progression. By ROC curve analysis, CTN was of statistically significance(P<0.05, 95%CI 0.558-0.834), but CEA was not(P>0.05). Adverse events were generally mild (grade 1 or 2),including hypertension (9 cases),skin rash (9 cases), and diarrhea (6 cases). Two patients developed grade 3 elevation of serum glutamate pyruvate transaminase and one patient developed grade 3 elevation of drug-related bowel disease. No grade 4 drug-related adverse event occurred. Conclusions: Vandetanib is effective and well tolerated for patients with locally advanced or metastatic MTC who have no chance for surgery. This indicates the increase of CTN is clinically relevant to disease progression, but the number of patients are extremely low, and, therefore further research is needed. Long-term use of vandetanib may cause resistance.

To explore the feasibility, safety and clinical effect of mid-frequency transcutaneous electrical acupoint stimulation (TEAS) combined with oral tamoxifen (TAM) in the treatment of oligoasthenozoospermia.

Objective To investigate the safety of a 60-minute rituximab rapid infusion protocol in the maintenance therapy for Chinese B-cell lymphoma patients (including the elderly) and to discuss the feasibility of rituximab treatment in outpatient departments or daily wards. Methods This prospective study enrolled 820 patients diagnosed with B cell lymphoma in the Department of Hematology of Peking Union Medical College Hospital from February 2015 to July 2016. From the second chemotherapy cycle,rituximab was infused within 60 minutes (100 mg/h over the first 15 minutes and the remaining dose given over 45 minutes, there was no maximum infusion rate,and 700 mg/h was acceptable),and the adverse reactions were recorded. Comparison was done between patients<65 years and≥65 years. Results The overall adverse reaction rate was 4.20% and no grade 4 or higher adverse reactions were recorded. The adverse reaction rate in the elderly patients was not significantly elevated. Conclusion For Chinese patients (including the elderly) with B cell lymphoma,the 60-minute rapid infusion of rituximab (beyond the first cycle) is a safe treatment option with low adverse reaction rate.