1.Exploring Pathogenesis and Treatment Principles of Chronic Obstructive Pulmonary Disease Based on Spleen-mitochondria Correlation
Shiyi WANG ; Miao YU ; Xinyao HE ; Zi WANG ; Haijun LUAN ; Yibo SUN ; Haotong WANG ; Linlin WANG ; Lijian PANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):258-264
According to the Qi-blood-body fluid theory and the association between the spleen in visceral manifestation theory of traditional Chinese medicine (TCM) and mitochondria in modern cellular biology, it is proposed that the role of the spleen in generating and transforming Qi and blood is analogous to the energy-producing function of mitochondria—both serving as fundamental power sources for vital activities of the human body. The spleen governs transportation and transformation, playing a critical role in energy metabolism and the digestion and absorption of nutrients. Similarly, mitochondria are vital for maintaining physiological functions such as cellular energy supply, cell survival, and overall human metabolism. Furthermore, spleen deficiency is closely linked to mitochondrial dysfunction. Accordingly, mitochondrial energy conversion and substance metabolism are regarded as the microscopic essence of the spleen's function in transportation and transformation. Spleen deficiency and mitochondrial dysfunction contribute to the formation of pathological products such as phlegm-turbidity and blood stasis. This aligns with the pathogenesis of chronic obstructive pulmonary disease (COPD), with Qi deficiency as the root cause and phlegm-turbidity and blood stasis as the manifestations. Therefore, the integrative treatment of COPD should follow the therapeutic principle of invigorating the spleen and reinforcing healthy Qi, while also resolving phlegm and removing blood stasis to address both root cause and manifestations. This approach can improve the mitochondrial function, regulate energy metabolism, and reduce oxidative stress levels to alleviate COPD symptoms, slow down disease progression, and improve prognosis. By integrating the holistic concept of TCM with molecular mechanisms of modern medicine, this paper explores the pathogenesis and therapeutic principles of COPD from the spleen-mitochondria correlation. It not only provides a new direction for the modern development of TCM and the integration of Chinese and Western medicine but also offers a theoretical foundation for the integrated treatment of chronic, complex age-related diseases.
2.Exploring Pathogenesis and Treatment Principles of Chronic Obstructive Pulmonary Disease Based on Spleen-mitochondria Correlation
Shiyi WANG ; Miao YU ; Xinyao HE ; Zi WANG ; Haijun LUAN ; Yibo SUN ; Haotong WANG ; Linlin WANG ; Lijian PANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):258-264
According to the Qi-blood-body fluid theory and the association between the spleen in visceral manifestation theory of traditional Chinese medicine (TCM) and mitochondria in modern cellular biology, it is proposed that the role of the spleen in generating and transforming Qi and blood is analogous to the energy-producing function of mitochondria—both serving as fundamental power sources for vital activities of the human body. The spleen governs transportation and transformation, playing a critical role in energy metabolism and the digestion and absorption of nutrients. Similarly, mitochondria are vital for maintaining physiological functions such as cellular energy supply, cell survival, and overall human metabolism. Furthermore, spleen deficiency is closely linked to mitochondrial dysfunction. Accordingly, mitochondrial energy conversion and substance metabolism are regarded as the microscopic essence of the spleen's function in transportation and transformation. Spleen deficiency and mitochondrial dysfunction contribute to the formation of pathological products such as phlegm-turbidity and blood stasis. This aligns with the pathogenesis of chronic obstructive pulmonary disease (COPD), with Qi deficiency as the root cause and phlegm-turbidity and blood stasis as the manifestations. Therefore, the integrative treatment of COPD should follow the therapeutic principle of invigorating the spleen and reinforcing healthy Qi, while also resolving phlegm and removing blood stasis to address both root cause and manifestations. This approach can improve the mitochondrial function, regulate energy metabolism, and reduce oxidative stress levels to alleviate COPD symptoms, slow down disease progression, and improve prognosis. By integrating the holistic concept of TCM with molecular mechanisms of modern medicine, this paper explores the pathogenesis and therapeutic principles of COPD from the spleen-mitochondria correlation. It not only provides a new direction for the modern development of TCM and the integration of Chinese and Western medicine but also offers a theoretical foundation for the integrated treatment of chronic, complex age-related diseases.
3.Comparison of the efficacy and safety between 1 470 nm laser en bloc resection of bladder tumor and transurethral resection of bladder tumor in treatment of non-muscle-invasive bladder cancer
Yang WANG ; Weiting PANG ; Weifeng YANG ; Haitian HE ; Xinming ZHANG ; Nan ZHANG ; Kebing WANG
China Journal of Endoscopy 2025;31(1):80-85
Objective To compare the clinical efficacy and safety of 1 470 nm laser en bloc resection of bladder tumor(1 470 nm-EBRBT)and transurethral resection of bladder tumor(TUR-BT).Methods Clinical data of 85 non-muscle-invasive bladder cancer(NMIBC)patients from June 2018 to June 2021 were analyzed retrospectively.The patients were divided into 1 470 nm-EBRBT group(n=40)and TUR-BT group(n=45)according to different surgical methods,the postoperative chemotherapy regimen of bladder perfusion was the same in both groups.The surgical safety,clinical efficacy,pathological results and recurrence free survival rate of two groups were recorded.Results There were no statistically significant differences in operation time,incidence of bladder perforation,and incidence of postoperative delayed hemorrhage between the two groups(P>0.05).Compared with the TUR-BT group,the 1 470 nm-EBRBT group had less blood loss,shorter bladder irrigation time,catheter indwelling time and postoperative hospital time,and no obturator nerve reflex,the differences were statistically significant(P<0.05).The proportion of detrusor in the first resected pathological specimens in 1 470 nm-EBRBT group was higher than that in TUR-BT group(P<0.05).There were no statistically significant differences in tumor recurrence rate of one year,tumor cumulative recurrence rate of two years and recurrence free survival time between the two groups(P>0.05).Conclusion Compared with traditional TUR-BT,1 470 nm-EBRBT is a safe and effective method,which has the advantages of complete pathological specimens,fewer complications,faster recovery and so on.Therefore,it is worthy of clinical application.
4.A preliminary study on the prognosis of condylar cartilage degeneration of rat temporomandibular osteo-arthritis treated with conditioned media of stem cells from human exfoliated deciduous teeth
Rui HE ; Xiaohua CHEN ; Yuchen DUAN ; Fan WU ; Feng HE ; Hui MIAO ; Shibin YU ; Jianliang PANG
Journal of Practical Stomatology 2025;41(5):581-587
Objective:This study aimed to evaluate whether intra-articular delivery of conditioned medium(CM)derived from stem cells of human exfoliated deciduous teeth(SHED)could influence the progression of condylar cartilage degeneration in a rat model of temporomandibular joint osteoarthritis(TMJ OA).Methods:Sixty 8-week-old male SD rats were randomly divided into control group(CON group),intraarticular injection of MIA induced TMJ OA model group(MIA group),and injection of SHED condi-tioned medium 1 week after MIA modeling for treatment group(SHED-CM group),with 20 animals in each group.Histological sec-tions,HE,Safranine O-solid green staining,Col Ⅱ immunohistochemical staining,and TUNEL staining were performed 2 and 4 weeks after the start of treatment.Western blotting and RT-qPCR were used to detect the key molecules of apoptosis,cleaved-CASP3,BAX and BCL2,pro-inflammatory related factors IL-1β,IL-6,TNFα,MMP3,ADAMTS5,and the MAPK pathway-related molecules p-ERK,ERK,p-P38 and P38.Results:Compared with the CON group and SHED-CM group,the condyle chondrocytes in the MIA group had disordered arrange-ment,interrupted layers,significantly thickened fibrous layers(P<0.001),and significantly increased Mankin's OA histological score(P<0.001).In the MIA group,both the Safranin O-positive area ratio and the proportion of ColⅡ-positive regions were markedly reduced compared with the CON and SHED-CM groups(P<0.001).Conversely,the proportion of TUNEL-positive cells was substantially higher than in the other two groups(both P<0.001).Western blot analysis further demonstrated that apoptotic markers(cleaved-CASP3,BAX/BCL2)and MAPK pathway-related proteins(p-ERK,ERK,p-P38,P38)were expressed at significantly elevated levels in the MIA group relative to CON and SHED-CM groups(BAX/BCL2:P<0.05;cleaved-CASP3:P<0.01;p-P38/P38:P<0.001;p-ERK/ERK:P<0.01).Similarly,qRT-PCR revealed upregulated expression of inflammatory mediators,including IL-1 β(P<0.001),IL-6(P<0.01),TNFα(P<0.01),MMP3(P<0.001),and ADAMTS5(P<0.05),in the MIA group compared with the CON and SHED-CM groups.Conclusion:SHED-CM treatment can ef-fectively reverse MIA-induced condylar cartilage degeneration of TMJ OA in rats.
5.Effectiveness of digital management platform led by outpatient specialist nurses in type 2 diabetes patients
Fang HE ; Xiang ZHOU ; Wenhua ZHOU ; Xiaojing WANG ; Na PANG ; Jie YU ; Xinhua XIAO
Chinese Journal of Modern Nursing 2025;31(35):4778-4783
Objective:To explore the effectiveness of digital management platform led by outpatient specialist nurses among patients with type 2 diabetes in outpatient settings.Methods:From March 2024 to March 2025, adult patients with type 2 diabetes who visited the Endocrinology Clinic at Peking Union Medical College Hospital were selected using convenience sampling. Patients were randomly assigned to the control group and intervention group using the random number table method. Patients in control group received routine education on type 2 diabetes during their clinic visits after enrollment. Intervention group was managed by nurses through a digital management platform, establishing long-term connections with patients. Based on the platform, nurses regularly provided patients with knowledge updates, promptly responded to patient inquiries, reviewed daily dietary records, monitored blood glucose data, conducted weekly telephone follow-ups, and scheduled regular clinic visits to precisely intervene in patients' lifestyles. The glycated hemoglobin (HbA1c) and self-management behavior scores were compared between two groups of patients before and after three months of intervention.Results:A total of 46 patients were enrolled and completed the 3-month follow-up, including 25 in control group and 21 in intervention group. There were no statistically significant differences in HbA1c or self-management behavior scores between the two groups of patients before intervention ( P>0.05). At three months of intervention, the HbA1c reduction in intervention group was greater than that in control group, with a statistically significant difference ( P<0.05). There was no statistically significant difference in Summary of Diabetes Self-Care Activities Scale scores between the two groups ( P>0.05). The difference in changes in diabetic foot self-screening scores between intervention group and control group was statistically significant ( P<0.05) . Conclusions:Specialist nurse-led precision health care management utilizing digital platforms can improve HbA1c and enhance self-management behaviors for diabetic foot in patients with type 2 diabetes, which is expected to be promoted and applied in the outpatient management of diabetes patients.
6.Effects of forward moving pelvic floor exercise program in urinary incontinence management among patients undergoing radical prostatectomy
Hang WANG ; Min LI ; Yunfang LI ; Jiaqi PAN ; Yaxin PANG ; Jiangting HE
Chinese Journal of Modern Nursing 2025;31(35):4828-4833
Objective:To explore the effect of the forward moving pelvic floor exercise program in urinary incontinence management among patients undergoing radical prostatectomy.Methods:From June 2022 to January 2024, 150 patients undergoing radical prostatectomy of the Urology Surgery Department, the First Affiliated Hospital of Zhengzhou University were selected using convenience sampling. Patients were randomly divided into an observation group and a control group, with 75 cases in each group. Control group received conventional perioperative management for prostate cancer, while observation group implemented a forward moving pelvic floor exercise program in addition to conventional management. The incidence of urinary incontinence, urinary control capabilities before and after intervention (including maximum urinary flow rate, average urinary flow rate, voided urine volume, and residual urine volume), and quality of life scores [evaluated using the Chinese version of the Incontinence Quality of Life Questionnaire (I-QOL) ] were compared between two groups of patients.Results:The incidence of urinary incontinence of observation group was lower than that of control group. Furthermore, patients with urinary incontinence in observation group exhibited significantly lower urine leakage volume and fewer episodes of urinary incontinence over 24 hours at one month postoperatively compared to control group, with statistically significant differences ( P<0.05). There were no statistically significant differences in maximum urinary flow rate, average urinary flow rate, voided urine volume, or residual urine volume between the two groups before intervention ( P>0.05). Following intervention, both groups demonstrated increased maximum urinary flow rate, average urinary flow rate, and voided urine volume compared to baseline, with observation group exhibiting higher values than control group ( P<0.05), and residual urine volume of both groups decreased compared to baseline, with observation group showing lower values than control group, these differences were statistically significant ( P<0.05). The difference in I-QOL scores between the two groups before intervention was not statistically significant ( P>0.05). Following intervention, I-QOL scores decreased in both groups, but observation group had higher score than control group, and the difference was statistically significant ( P<0.05) . Conclusions:The forward moving pelvic floor exercise program effectively reduces the incidence of urinary incontinence in patients undergoing radical prostatectomy, alleviates the severity of incontinence, and improves both urodynamic outcomes and quality of life.
7.Anti-inflammatory effects of celastrol on experimentally induced pulpitis in rats
Jiahao TANG ; Lei PANG ; Hao ZHANG ; Li HE
Chinese Journal of Immunology 2025;41(10):2444-2449
Objective:To investigate anti-inflammatory effects of celastrol as pulp capping agent on experimental pulpitis in rats and to explore its mechanism.Methods:Rat model of experimental pulpitis was established by lipopolysaccharide(LPS).A total of 28 rats were randomly divided into 4 groups(model group,calcium hydroxide group,celastrol group,drug mixture group).After 5 days,the rats were sacrificed and the maxillary and molar specimens were obtained.Pathological changes of pulp tissue were observed by HE staining,as well as the inflammation level was evaluated by a modified histological scoring system.Relative mRNA expression levels of TNF-α and IL-β in dental pulp were detected by qRT-PCR.Western blot was used to assess phosphorylation level of NF-κB p65 in dental pulp.Results:Histological scores of celastrol group and drug mixture group were significantly lower than those of model group and calcium hydroxide group(P<0.01),while there was no significant statistical differences between celastrol group and drug mixture group(P>0.05).Compared with model group,levels of TNF-α and IL-1β mRNA in pulp tissue of calcium hydroxide group,celastrol group and drug mixture group were decreased(P<0.05).Western blot showed that treatment of celastrol and mixed drugs could considerably reduce phosphorylation level of NF-κB p65 in rat pulp tissue.Conclusion:Celastrol can relieve experimental pulpitis in rats,and its mechanism may be related to the inhibition of NF-κB p65 activation and reduce the expressions of TNF-α and IL-1β.
8.Safety and efficacy of the Neuroform EZ stent in treating severe symptomatic intracranial atherosclerotic stenosis
Ziang CHEN ; Wenbo LIU ; Dehua GUO ; Yanyan HE ; Mengyue LIU ; Yang ZHAO ; Yukuan PANG ; Tianxiao LI ; Yingkun HE
Chinese Journal of Cerebrovascular Diseases 2025;22(10):721-730
Objective To evaluate the safety and efficacy of the Neuroform EZ self expanding stent for severe symptomatic intracranial atherosclerotic stenosis(sICAS).Methods Retrospectively enrolled consecutive patients with severe sICAS who underwent percutaneous transluminal angioplasty and stenting(PTAS)with a Neuroform EZ stent in the Department of Cerebrovascular Disease,Henan Provincial People's Hospital,from March 2020 to December 2022.Baseline demographic and clinical data were collected,including age,sex,hypertension,diabetes mellitus,coronary artery disease,dyslipidemia,hyperhomocysteinemia,transient ischemic attack(TIA)and ischemic stroke,smoking history,modified Rankin scale(mRS)score at admission,and National Institutes of Health stroke scale(NIHSS)score.Preoperative imaging data included target vessel(basilar artery,intracranial segment of the internal carotid artery,middle cerebral artery,and intracranial vertebral artery),lesion length,degree of stenosis,and vascular morphology according to the Mori classification(type A,lesion length<5 mm with concentric or moderately eccentric stenosis;type B,lesion length<10 mm with severely eccentric stenosis;type C,lesion length>10 mm or arterial angulation>90°).Technical success was defined as accurate delivery and deployment of the stent with complete coverage of the target lesion and immediate post deployment residual stenosis<50%.Postoperative head CT was performed to detect intracranial hemorrhage.Periprocedural complications were recorded,including intracranial hemorrhage,arterial dissection,in stent thrombosis,and perforator occlusion occurring intraoperatively within 72 hours after the procedure.At one-month post-operation,patients were seen through outpatient follow-up for TIA,hemorrhagic or ischemic stroke,and all cause death.At 6 months after surgery,DSA or CT angiography(CTA)was performed to assess in stent restenosis(ISR,defined as>50%stenosis within the stent or within5mm of its edges,or>20%luminal loss).At 1 and 2 years postoperatively,ipsilateral ischemic stroke or TIA recurrence was assessed by outpatient visit or telephone follow up.Results A total of 76 patients with severe sICAS underwent PTAS with a Neuroform EZ stent(56 males,20 females,age 47-80 years,with a mean age of[61±10]years).(1)Within all patients enrolled,40 had middle cerebral artery,16 with basilar artery,6 with intracranial vertebral artery and 14 with intracranial internal carotid artery.The preprocedural lesion length was 2-15 mm,with a mean length of(6.2±2.5)mm,and stenosis severity was70%-99%,the mean severity was(83.2±6.9)%,with Mori type B being the most common type(57.9%[44/76]).(2)PTAS was successfully completed on all patients(technical success 100%).Pre dilation with a conventional balloon was performed in all cases(using balloon with diameter of 1.5-3.5mm,and stent with diameter of 2.5-4.5 mm and length of 15-30 mm).Immediate post procedural residual stenosis was(17.4±9.0)%,significantly lower than baseline(t=52.9,P<0.05),with a mean difference of 65.8%(95%CI63.3%-68.3%).(3)Among all 76patients,one patient developed a flow limiting dissection post balloon angioplasty,which recovered after stent deployment.One patient with basilar artery stenosis experienced recurrent ischemic stroke at 5-day postoperatively,presenting with right sided weakness and coughing on liquids.Imaging showed an acute infarct in the left pons,considered perforator occlusion.The overall periprocedural complication rate was 2.6%(2/76).(4)No deaths occurred within 30 days after surgery.Sixty nine patients(90.8%)underwent 6 month imaging follow up with DSA(52 cases)or CTA(17 cases).ISR occurred in 12 patients(17.4%),including 6 asymptomatic and 6symptomatic cases.The ipsilateral ischemic stroke recurrence rate was 6.6%(5/76)at1 year and13.2%(10/76)at2years.Conclusions Neuroform EZstent assisted PTASappears safe and feasible for the treatment of severe sICAS.The long term effectiveness requires confirmation in large,multicenter,prospective studies.
9.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
10.Risk factors for poor graft function after allogeneic hematopoietic stem cell transplantation in children with transfusion dependent thalassemia
Guanxiu PANG ; Wenguang JIA ; Jianming LUO ; Yunyan HE
Chinese Journal of Pediatrics 2025;63(11):1201-1206
Objective:To analyze the risk factors and outcomes of poor graft function (PGF) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with transfusion dependent thalassemia (TDT).Methods:A retrospective cohort study was conducted in 118 pediatric TDT patients who underwent allo-HSCT at the First Affiliated Hospital of Guangxi Medical University from June 30, 2018 to December 31, 2022. Based on PGF diagnostic criteria, patients were categorized into PGF group and good graft function (GGF) group. Clinical features, including pre-transplant baseline characteristics and post-transplant complications were compared between groups by χ2 test or Fisher exact test. Logistic regression identified PGF risk factors and model performance was assessed by receiver operating characteristic (ROC) curve analysis. Survival analysis was conducted using the Kaplan-Meier method with Log-Rank test. Results:Among 118 patients, there were 69 males (58.5%) and 49 females (41.5%). Fifteen cases (12.7%) developed PGF while 103 cases (87.3%) achieved GGF. Compared to the GGF group, the PGF group had significantly higher rates of age ≥10 years at transplant, interval from diagnosis to transplant ≥6.7 years, human leukocyte antigen (HLA) mismatch, ABO mismatch, post-transplant BK virus infection, and hemorrhagic cystitis (all P<0.05). Multivariate analysis identified independent risk factors for PGF: age ≥10 years at transplant ( OR=27.20, 95% CI 2.11-350.91), interval from diagnosis to transplant ≥6.7 years ( OR=23.23, 95% CI 1.39-388.23), post-transplant cytomegalovirus (CMV) infection ( OR=57.83, 95% CI 3.01-1 111.71), and post-transplant BK virus infection ( OR=67.73, 95% CI 2.56-1 794.52). The ROC curve showed an area under curve of 0.92 (95% CI 0.86-0.97, P<0.001). The 4-year overall survival rate was significantly lower in the PGF group compared to the GGF group ((53.3±12.9)% vs.(90.2±2.9)% ,χ2=16.49, P<0.001). Conclusions:Risk factors for PGF in TDT children after allo-HSCT include age ≥10 years at transplant, interval from diagnosis to transplant ≥6.7 years, post-transplant CMV infection and post-transplant BK virus infection. The PGF patients after allo-HSCT exhibit significantly poorer overall survival compared to those with GGF.

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