1.Comprehensive management ability of Helicobacter pylori screening in primary hospitals of Jiangsu Province
Jinjin SHI ; Zixiang HUANG ; Wei SU ; Cheng LI ; Long YE ; Hailing FENG ; Shuowei XING ; Hongmei YANG ; Guoxin ZHANG ; Feng YE
Chinese Journal of Digestion 2025;45(8):520-525
Objective:Based on the activities of Helicobacter pylori ( HP) screening in Jiangsu Province in 2024, to evaluate the overall management ability in HP screening, testing, treatment and follow-up in primary medical facilities. Methods:From May 15 to October 18, 2024, the data of HP screening and treatment were retrospectively collected from 79 township health centers, community hospitals, and community health service centers in Jiangsu Province. The rates of screening completion, urea breath test (UBT) completion, treatment rate, UBT follow-up completion, and HP eradication were analyzed. Chi-square test was used for statistical analysis. Results:The completion rate of HP screening was 94.45% (15 489/16 400). There were 6 604 cases (42.64%) with serum HP antibody positive among the 15 489 individuals who completed screening. The positive rate of serum HP antibody in males was higher than that in females (44.77%, 2 643/5 904 vs. 41.32%, 3 961/9 585), and the difference was statistically significant ( χ2=17.69, P<0.001). The positive rates of serum HP antibody in screened individuals aged 18 to 19, 20 to 39, 40 to 59, and 60 to 75 years old were 22.38% (32/143), 36.12% (1 168/3 234), 45.01% (3 240/7 199), and 44.05% (2 164/4 913), respectively, and the difference was statistically significant( χ2=100.73, P<0.001). Among the 6 604 HP antibody-positive individuals, 4 381 cases completed UBT, with a UBT completion rate of 66.34% (4 381/6 604). There were 3 197 individuals with both HP serum antibody and UBT positive, the consistency rate of the 2 tests was 72.97% (3 197/4 381). Totally 2 737 cases received treatment, with a treatment completion rate of 85.61% (2 737/3 197); 2 327 individuals underwent UBT follow-up, with a follow-up completion rate of 85.02% (2 327/2 737). During follow-up, the result of UBT was negative in 1 982 individuals, and the HP eradication rate was 85.17% (1 982/2 327). Conclusions:There are deficiencies in the completion rate of HP screening, testing, treatment, and follow-up in primary hospitals, especially in the completion rate of UBT, which may be related to cognitive insufficiency for HP in residents. It is necessary to strengthen the training of physicians′ abilities in primary hospitals, optimize the allocation of drug resources, enhance health education, and increase residents′ participation and compliance.
2.Ureteroscopy-assisted flexible ureteroscopic lithotripsy in the treatment of transplanted kidney stones: a report of 9 cases and literature review
Biao DONG ; Bo CHEN ; Ning WANG ; Jinjin FENG ; Xuepei ZHANG
Chinese Journal of Organ Transplantation 2025;46(8):599-605
Objective:To investigate the clinical application effect and preliminary experience of ureteroscopy-assisted flexible ureteroscopic lithotripsy in the treatment of transplanted kidney stones.Method:A retrospective analysis was conducted on the clinical data of 9 kidney transplant recipients with graft stones who underwent ureteroscopy-assisted flexible ureteroscopic lithotripsy at the First Affiliated Hospital of Zhengzhou University between January 2020 and January 2023. The recipients' general information, surgical procedures, and postoperative outcomes were reviewed and summarized. Additionally, a comprehensive literature search was performed in both Chinese and international databases, including CNKI, Wanfang, and the China Academic Journals Full-text Database, as well as PubMed and Web of Science. The search terms included " kidney transplant" "flexible ureteroscope" "ureteroscope" and " urinary tract stones" . The search covered all publications available up to December 2023.Result:The 9 recipients had a mean age of 37. 56 years (range: 27–54 years) . The onset time of the kidney stones ranged from 1 to 13 months after kidney transplantation. All recipients were diagnosed with transplanted kidney stones by CT and showed no symptoms of kidney colic at the time of onset. All transplanted kidneys were located in the right iliac fossa, with varying degrees of hydronephrosis. The smallest stone diameter was 0. 5 cm, and the largest was 1. 3 cm. The number of stones ranged from 1 to 3 per recipient; 6 cases had solitary stones, and 3 had multiple stones in the renal pelvis and calyces. In all 9 surgeries, the ureteral orifice of the transplanted kidney was located at the apex of the bladder using ureteroscopy, and a hydrophilic guidewire was inserted into the renal pelvis. A second ureteroscopy was then performed, guiding the ureteroscope tip into the transplanted ureteral orifice in coaxial alignment with the guidewire. A flexible ureteroscope sheath was advanced along the guidewire, followed by the insertion of a digital flexible ureteroscope to perform holmium laser dusting lithotripsy. Stone composition analysis revealed mixed calcium oxalate monohydrate and calcium oxalate dihydrate. The surgical duration ranged from 30 to 75 minutes. No complications such as massive bleeding, septic shock, or rejection occurred. Postoperative review at 1 month, after ureteral stent removal, showed no residual stones in any patient. During 6 months of follow-up, no recurrence of stones was observed, and the renal function of the transplanted kidneys remained stable compared to preoperative levels. A total of 19 related articles were identified through literature review, including 11 in English and 8 in Chinese. Chinese reports on transplanted kidney stones were all from single-center studies with small case numbers. In contrast, foreign meta-analyses and multicenter studies showed that treatments for transplanted kidney stones abroad mainly included antegrade/retrograde ureteroscopy and percutaneous nephroscopy.Conclusion:Ureteroscopy-assisted flexible ureteroscopic lithotripsy is a feasible treatment for transplanted kidney stones. It can effectively protect graft kidney function and has promising clinical application prospects.
3.Establishment and optimization of a genetic manipulation system for Staphylococcus pasteuri.
Tinghao ZHANG ; Ziqi WANG ; Yuxin SONG ; Jinjin WANG ; Feng GUO ; Yongjun ZHANG ; Fuping LU ; Ming LI
Chinese Journal of Biotechnology 2025;41(9):3604-3616
One of the technical bottlenecks limiting the high yield of 1,4-butanediamine is the insufficient tolerance of strains to 1,4-butanediamine. Enhancing the tolerance of strains to 1,4-butanediamine is therefore a primary challenge that needs to be addressed for the construction of strains with high yields of 1,4-butanediamine. Staphylococcus pasteuri 326180 exhibits exceptional tolerance to high-concentration 1,4-butanediamine, serving as both an ideal model for studying the mechanism underlying the 1,4-butanediamine tolerance and a novel host for constructing strains capable of efficiently producing 1,4-butanediamine. However, for both the research on the tolerance mechanism and the modification of chassis strains, gene editing of S. pasteuri needs to be carried out at the molecular level. The research objective of this paper is to establish a genetic manipulation system for S. pasteuri, laying foundation for subsequent studies on tolerance mechanism and the modification of chassis strains. This study systematically optimized the electroporation conditions, including key parameters such as the growth phase of cells, electric field strength, electroporation buffer, and recovery medium, successfully establishing an electroporation method for S. pasteuri. Additionally, we constructed the gene editing plasmid pCpfOA by replacing the resistance expression cassette, optimized the selection markers for gene editing, and finally established a CRISPR/Cpf1-based gene editing technology for S. pasteuri, achieving an editing efficiency of 90%. The genetic manipulation system of S. pasteuri established in this study provides technical support for research into the tolerance mechanism of this bacterium and the genetic modification of chassis strains.
Staphylococcus/drug effects*
;
Gene Editing/methods*
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Electroporation/methods*
;
Plasmids/genetics*
;
CRISPR-Cas Systems
;
Genetic Engineering/methods*
4.Comprehensive management ability of Helicobacter pylori screening in primary hospitals of Jiangsu Province
Jinjin SHI ; Zixiang HUANG ; Wei SU ; Cheng LI ; Long YE ; Hailing FENG ; Shuowei XING ; Hongmei YANG ; Guoxin ZHANG ; Feng YE
Chinese Journal of Digestion 2025;45(8):520-525
Objective:Based on the activities of Helicobacter pylori ( HP) screening in Jiangsu Province in 2024, to evaluate the overall management ability in HP screening, testing, treatment and follow-up in primary medical facilities. Methods:From May 15 to October 18, 2024, the data of HP screening and treatment were retrospectively collected from 79 township health centers, community hospitals, and community health service centers in Jiangsu Province. The rates of screening completion, urea breath test (UBT) completion, treatment rate, UBT follow-up completion, and HP eradication were analyzed. Chi-square test was used for statistical analysis. Results:The completion rate of HP screening was 94.45% (15 489/16 400). There were 6 604 cases (42.64%) with serum HP antibody positive among the 15 489 individuals who completed screening. The positive rate of serum HP antibody in males was higher than that in females (44.77%, 2 643/5 904 vs. 41.32%, 3 961/9 585), and the difference was statistically significant ( χ2=17.69, P<0.001). The positive rates of serum HP antibody in screened individuals aged 18 to 19, 20 to 39, 40 to 59, and 60 to 75 years old were 22.38% (32/143), 36.12% (1 168/3 234), 45.01% (3 240/7 199), and 44.05% (2 164/4 913), respectively, and the difference was statistically significant( χ2=100.73, P<0.001). Among the 6 604 HP antibody-positive individuals, 4 381 cases completed UBT, with a UBT completion rate of 66.34% (4 381/6 604). There were 3 197 individuals with both HP serum antibody and UBT positive, the consistency rate of the 2 tests was 72.97% (3 197/4 381). Totally 2 737 cases received treatment, with a treatment completion rate of 85.61% (2 737/3 197); 2 327 individuals underwent UBT follow-up, with a follow-up completion rate of 85.02% (2 327/2 737). During follow-up, the result of UBT was negative in 1 982 individuals, and the HP eradication rate was 85.17% (1 982/2 327). Conclusions:There are deficiencies in the completion rate of HP screening, testing, treatment, and follow-up in primary hospitals, especially in the completion rate of UBT, which may be related to cognitive insufficiency for HP in residents. It is necessary to strengthen the training of physicians′ abilities in primary hospitals, optimize the allocation of drug resources, enhance health education, and increase residents′ participation and compliance.
5.Ureteroscopy-assisted flexible ureteroscopic lithotripsy in the treatment of transplanted kidney stones: a report of 9 cases and literature review
Biao DONG ; Bo CHEN ; Ning WANG ; Jinjin FENG ; Xuepei ZHANG
Chinese Journal of Organ Transplantation 2025;46(8):599-605
Objective:To investigate the clinical application effect and preliminary experience of ureteroscopy-assisted flexible ureteroscopic lithotripsy in the treatment of transplanted kidney stones.Method:A retrospective analysis was conducted on the clinical data of 9 kidney transplant recipients with graft stones who underwent ureteroscopy-assisted flexible ureteroscopic lithotripsy at the First Affiliated Hospital of Zhengzhou University between January 2020 and January 2023. The recipients' general information, surgical procedures, and postoperative outcomes were reviewed and summarized. Additionally, a comprehensive literature search was performed in both Chinese and international databases, including CNKI, Wanfang, and the China Academic Journals Full-text Database, as well as PubMed and Web of Science. The search terms included " kidney transplant" "flexible ureteroscope" "ureteroscope" and " urinary tract stones" . The search covered all publications available up to December 2023.Result:The 9 recipients had a mean age of 37. 56 years (range: 27–54 years) . The onset time of the kidney stones ranged from 1 to 13 months after kidney transplantation. All recipients were diagnosed with transplanted kidney stones by CT and showed no symptoms of kidney colic at the time of onset. All transplanted kidneys were located in the right iliac fossa, with varying degrees of hydronephrosis. The smallest stone diameter was 0. 5 cm, and the largest was 1. 3 cm. The number of stones ranged from 1 to 3 per recipient; 6 cases had solitary stones, and 3 had multiple stones in the renal pelvis and calyces. In all 9 surgeries, the ureteral orifice of the transplanted kidney was located at the apex of the bladder using ureteroscopy, and a hydrophilic guidewire was inserted into the renal pelvis. A second ureteroscopy was then performed, guiding the ureteroscope tip into the transplanted ureteral orifice in coaxial alignment with the guidewire. A flexible ureteroscope sheath was advanced along the guidewire, followed by the insertion of a digital flexible ureteroscope to perform holmium laser dusting lithotripsy. Stone composition analysis revealed mixed calcium oxalate monohydrate and calcium oxalate dihydrate. The surgical duration ranged from 30 to 75 minutes. No complications such as massive bleeding, septic shock, or rejection occurred. Postoperative review at 1 month, after ureteral stent removal, showed no residual stones in any patient. During 6 months of follow-up, no recurrence of stones was observed, and the renal function of the transplanted kidneys remained stable compared to preoperative levels. A total of 19 related articles were identified through literature review, including 11 in English and 8 in Chinese. Chinese reports on transplanted kidney stones were all from single-center studies with small case numbers. In contrast, foreign meta-analyses and multicenter studies showed that treatments for transplanted kidney stones abroad mainly included antegrade/retrograde ureteroscopy and percutaneous nephroscopy.Conclusion:Ureteroscopy-assisted flexible ureteroscopic lithotripsy is a feasible treatment for transplanted kidney stones. It can effectively protect graft kidney function and has promising clinical application prospects.
6.Preparation of heparinized acellular vascular scaffold and hemocompatibility evaluation
Xiafei LI ; Lingling ZHAO ; Feng LIANG ; Xuewei ZHANG ; Jinjin ZHANG ; Fei LIN ; Tuo YANG ; Liang ZHAO
Chinese Journal of Tissue Engineering Research 2024;28(17):2631-2636
BACKGROUND:Acellular vascular scaffolds can mimic the microstructure and function of native blood vessels,but some extracellular matrix loss occurs during their preparation,which affects their hemocompatibility.Therefore,it is necessary to modify them to improve their hemocompatibility. OBJECTIVE:To assess the hemocompatibility of acellular vascular scaffold prepared by Triton-x100/heparin sodium treatment. METHODS:The abdominal aorta was taken from SD rats and randomly divided into control and experimental groups.The control group was treated with Triton-x100 for 48 hours.The experimental group was treated with Triton-x100 for 48 hours and then treated with heparin sodium.The morphology and hydrophilicity of the two groups of acellular vascular scaffolds were detected.The hemocompatibility of the two groups of acellular vascular scaffold was evaluated by recalcification coagulation time test,platelet adhesion test,dynamic coagulation time test,hemolysis test,and complement activation test. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the two groups of vascular scaffolds was relatively intact,and a large number of fiber filaments appeared on the surface of the scaffolds after decellularity treatment,and the surface microstructure changed significantly.The water contact angle of the two groups of vascular scaffolds was smaller than that of natural vessels(P<0.000 1).There was no significant difference in water contact angle between the two groups(P>0.05).(2)The coagulation time of vascular scaffold was longer in the experimental group than in the control group(P<0.05).The number of platelets attached to the scaffold membrane was less in the experimental group than that in the control group(P<0.000 1).The coagulation index was greater in the experimental group than that in the control group(P<0.01),and the complement level was lower in the experimental group than that in the control group(P<0.001).The hemolysis rate of the two groups was lower than 5%of the national standard.(3)To conclude,acellular scaffold treated with Triton-x100/heparin sodium has excellent hemocompatibility.
7.Effects of governor vessel electroacupuncture on oxidative stress in rats with post-stroke limb spasm based on the glutathione antioxidant system
Jianyun ZHANG ; Jinjin MEI ; Shuaidi ZHANG ; Changyu GU ; Jingjing LI ; Jian GUO ; Xiaodong FENG ; Ruiqing LI
Journal of Beijing University of Traditional Chinese Medicine 2024;47(1):124-132
Objective To evaluate the mechanism of governor vessel electroacupuncture in rats with post-stroke limb spasm by observing the changes of glutathione antioxidant system-related factors.Methods A total of 60 SD rats were randomly divided into the normal group(n=12),sham operation group(n=12)and modeling group(n=36).The middle cerebral artery obstruction model was prepared by thread approach method in the modeling group,and 24 rats with successful modeling were randomly divided into the model group and the electroacupuncture group,with 12 rats in each group.At the 3rd day after modeling,the electroacupuncture group was treated with electroacupuncture at three acupoints of the governor vessel,namely,"Dazhui"(GV14),"Jizhong"(GV6)and"Houhui"(anteromedial of the transverse process of the sixth lumbar vertebra),for 30 min each time,once a day for 7 days.The neurological function of rats was assessed by Zea Longa neurological deficit score.The muscle tension of rats was detected by modified Ashworth dystonia rating and electrophysiological tracing method.The brain tissue water content was measured by the dry-wet weight method.The volume of cerebral infarction of rats was measured by the TTC staining method.The contents of glutathione(GSH),catalase(CAT),oxidized glutathione(GSSG),superoxide dismutase(SOD),and malondialdehyde(MDA)in the cortex of rats were detected by colorimetry.The protein and mRNA expressions of glutathione reductase(GR),glutamate cysteine ligase(GCL)C,GCLM,and glutathione peroxidase 4(GPX4)in the cortex of rats were measured by Western blotting and real-time PCR,respectively.Results Compared with rats in the normal and sham operation groups,the Zea Longa neurological deficit score,modified Ashworth dystonia rating,the volume of cerebral infarction,brain tissue water content,and GSSG and MDA contents in cortex were increased in the model group,the tension signal value and the proteins and mRNA expressions of GR,GCLC,GCLM,and GPX4 in cortex were decreased,and the contents of GSH,CAT,and SOD in cortex were decreased(P<0.05).Compared with the model group,the Zea Longa neurological deficit score,modified Ashworth dystonia rating,the volume of cerebral infarction,brain tissue water content,and GSSG and MDA contents in cortex were decreased in the electroacupuncture group,the tension signal value and the proteins and mRNA expressions of GR,GCLC,GCLM,and GPX4 in cortex were increased,and the contents of GSH,CAT,and SOD in cortex were increased(P<0.05).Conclusion Governor vessel electroacupuncture can improve the severity of post-stroke limb spasm in rats,and its mechanism may be related to the regulation of glutathione antioxidant system in cerebral cortex.
8.Effect of intraoperative continuous pump infusion of remimazolam on postoperative delirium in eld-erly patients with hip fracture
Henghua LIU ; Jinjin YANG ; Di QIU ; Peilan TENG ; Jianjun YANG ; Jiying FENG
The Journal of Clinical Anesthesiology 2024;40(10):1063-1067
Objective To observe the effect of intraoperative continuous pump infusion of remima-zolam on postoperative delirium(POD)in elderly patients with hip fracture under subarachnoid block.Methods A total of 236 elderly patients undergoing elective hip fracture surgery under subarachnoid block,82 males and 154 females,aged≥65 years,BMI 18.5-31.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were divided into two groups by using the randomized number table method:remimazolam group(group R)and control group(group C),118 patients in each group.When the surgical site was disinfected and cov-ered,the patients in group R were administered the first dose of reminmazolam 0.1 mg/kg and followed by a continuous infusion 0.2 mg·kg-1·h-1 intravenously to maintain the modified observer's assessment of alert/sedation(MOAA/S)1 or 2 scores.Reminmazolam infusion was stopped at the end of the surgery.The same volume of normal saline was injected for patients in group C.POD was assessed by the confusion as-sessment method-Chinese revised version(CAM-CR)1-3 days after the surgery.The anxiety scores one day before and one day after the surgery,and plasma cortisol concentrations when the patients were admitted into the operating room and at the end of the surgery were recorded.The incidence of intraoperative hypertension,hypotension,bradycardia,hypoxemia,and postoperative nausea and vomiting were also recor-ded.Results Compared with group C,POD incidence in group R was significantly decreased(P<0.05),anxiety score one day after surgery and plasma cortisol concentration at the end of the surgery in group R were significantly decreased(P<0.05),and the incidence of intraoperative hypertension in group R was significantly decreased(P<0.05).There were no significant differences in the plasma cortisol con-centrations when the patients were admitted into the operating room and the incidences of intraoperative hy-potension,bradycardia,hypoxemia,and postoperative nausea and vomiting between the two groups.Conclusion Remimazolam can reduce the incidence of postoperative delirium in elderlypatients undergoing hip fracture surgery under subarachnoid block,which may be related to alleviating intraoperative anxiety and inhibiting intraoperative stress response.
9.QL1604 plus paclitaxel-cisplatin/ carboplatin in patients with recurrent or metastatic cervical cancer:an open-label, single-arm, phase II trial
Cheng FANG ; Yun ZHOU ; Yanling FENG ; Liping HE ; Jinjin YU ; Yuzhi LI ; Mei FENG ; Mei PAN ; Lina ZHAO ; Dihong TANG ; Xiumin LI ; Buzhen TAN ; Ruifang AN ; Xiaohui ZHENG ; Meimei SI ; Baihui ZHANG ; Lingyan LI ; Xiaoyan KANG ; Qi ZHOU ; Jihong LIU
Journal of Gynecologic Oncology 2024;35(6):e77-
Objective:
QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
Methods:
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Results:
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
Conclusion
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.
10.QL1604 plus paclitaxel-cisplatin/ carboplatin in patients with recurrent or metastatic cervical cancer:an open-label, single-arm, phase II trial
Cheng FANG ; Yun ZHOU ; Yanling FENG ; Liping HE ; Jinjin YU ; Yuzhi LI ; Mei FENG ; Mei PAN ; Lina ZHAO ; Dihong TANG ; Xiumin LI ; Buzhen TAN ; Ruifang AN ; Xiaohui ZHENG ; Meimei SI ; Baihui ZHANG ; Lingyan LI ; Xiaoyan KANG ; Qi ZHOU ; Jihong LIU
Journal of Gynecologic Oncology 2024;35(6):e77-
Objective:
QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.
Methods:
This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment.
Results:
Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%).
Conclusion
QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

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