1. Determination of docusate sodium by ion-pair high-performance liquid chromatography
Lirong CAI ; Haiping SHU ; Sha XIAO ; Yue TAN ; Jinfeng ZHENG ; Changliang LI ; Yanming LIU
Journal of China Pharmaceutical University 2025;56(2):183-187
To reduce the dependency on high-carbon-load chromatographic columns,a new method has been established for the determination of the content of docusate sodium using ion-pair high-performance liquid chromatography (IP-HPLC). Tetrapropylammonium chloride was used as the ion-pair reagent with a mobile phase, composition of acetonitrile:10 mmol/L tetrapropylammonium chloride solution = 66∶34, adjusting pH to 6.5 with 0.1% phosphoric acid solution,flow rate of 1.5 mL/min, detection wavelength of 214 nm,column temperature of 35 °C, and an injection volume of 25 μL,and quantified by an external standard method. The main peak of docusate sodium exhibited a tailing factor of 1.34. The method showed good linearity within the range of 0.02 mg/mL to 0.40 mg/mL, with a correlation coefficient (r) of 0.999 9. It also demonstrated good repeatability, with recovery ranging from 97.0% to 98.2% (n=6). The quantification limit was 3.31 μg/mL, and the detection limit was 2.76 μg/mL.In summary,the new method shows good durability, a wide linear range, and high sensitivity, it is suitable for the determination of docusate sodium.
2.Effect of auricular therapy on sleep improvement and the GABAergic system pathway in an insomnia rat model
Hao CHEN ; Xifen ZHANG ; Xuesong WANG ; Yuanbo GAO ; Xuxin LI ; Xihui ZHENG ; Yu WANG ; Xiaojun ZHENG ; Haiping LI ; Yanfen SHE
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):138-148
Objective:
To investigate the effect of auricular therapy on sleep improvement and the GABAergic system pathway in a rat model of insomnia and to explore its possible mechanism.
Methods:
According to the random number table, 60 male SD rats were randomly divided into blank control, model, auricular point sticking, auricular bloodletting, and auricular bloodletting combined with sticking groups, with 12 rats per group. Insomnia was induced by intraperitoneal injection of p-chlorophenylalanine. After establishing the insomnia model, 36 rats were treated once a day with auricular point sticking or bloodletting for 5 consecutive days. After the intervention, the general condition and body weight of rats were observed; the righting reflex test was used to detect the sleep latency and duration; HE staining was used to observe the morphology of hypothalamic neuron cells; and an enzyme-linked immunosorbent assay was used to detect the GABA and glutamate content in rat serum. Immunohistochemistry(IHC) and real-time fluorescence quantitative PCR were used to detect GABA ARα1 and GABA ARγ2 protein and mRNA expression in the hypothalamus of rats, and Western blotting(WB) was used to detect GABA ARα1, GABA ARγ2, GAD65/67, GAT-1, and GABA-T protein expression in the hypothalamus of rats.
Results:
Compared with the blank control group, the model group had a lower body weight, a significantly shorter sleep duration (P<0.05), severe damage to the morphological structure of hypothalamic neurons with disordered cell arrangement, larger intercellular gaps, enlarged cell bodies, and a vacuolated appearance. All the intervention groups had significantly higher body weight and longer sleep duration than the model group (P<0.05). Compared with the other intervention groups, the auricular point sticking group had a longer sleep duration (P<0.05), and the hypothalamic neuron cells in all intervention groups improved, with the auricular point sticking group showing more apparent improvement. The model group had a lower GABA and higher glutamate contents, and GABA ARα1, GABA ARγ2, and GAD65/67 protein expression in the hypothalamus were lower than in the blank control group. In contrast, GAT-1 and GABA-T protein expression was higher, and GABA ARα1 and GABA ARγ2 mRNA expression was lower (P<0.05). The serum GABA content in the auricular point sticking and auricular bloodletting groups was higher, and the serum glutamate content in the auricular point sticking and auricular bloodletting combined sticking groups was lower than in the model group. GABA ARα1 mRNA expression in the hypothalamus of each intervention group was significantly increased, and GABA ARγ2 mRNA expression in the hypothalamus of the auricular point sticking and auricular bloodletting combined sticking groups increased. GABA ARα1(IHC, WB), GABA ARγ2(WB), and GAD65/67 protein expression in the hypothalamus of the auricular point sticking group increased, whereas GAT-1 and GABA-T protein expression decreased. GABA ARα1 and GABA ARγ2 protein expression(IHC, WB) in the hypothalamus of the auricular bloodletting group increased, whereas GABA-T protein expression decreased. GABA ARγ1(IHC) and GABA ARγ2(WB) protein expression in the hypothalamus of the auricular bloodletting combined sticking group increased, whereas GAT-1 and GABA-T protein expression decreased (P<0.05). Compared with in the inventation groups, the serum GABA content in the auricular point sticking group increased, the serum glutamate content decreased, GABA ARα1 and GABA ARγ2 mRNA expression in the hypothalamus increased, and GABA ARα1(IHC), GAD65/67 protein expression increased. In contrast, GABA-T protein expression decreased (P<0.05), and GABA ARγ2 protein expression(IHC) in the hypothalamus of the auricular bloodletting group increased (P<0.05).
Conclusion
Auricular therapy, particularly auricular point sticking, may have modulated the GABAergic system pathway by upregulating hypothalamic GABA ARα1, GABA ARγ2, and GAD65/67 protein expression while downregulating GAT-1 and GABA-T protein expression to alleviate symptoms in an insomnia rat model.
3.Study on surface microcirculation sensitization of acupuncture points related to cold coagulation and stasis syndrome in primary dysmenorrhea
Xuxin LI ; Xuesong WANG ; Miao LIN ; Mingjian ZHANG ; Yuanbo GAO ; Xifen ZHANG ; Hao CHEN ; Haiping LI ; Xiaojun ZHENG ; Xisheng FAN ; Jun LIU ; Juncha ZHANG ; Yanfen SHE
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):253-269
Objective:
To assess the dynamic changes of microcirculation at acupoints in patients with primary dysmenorrhea and cold congelation and blood stasis syndrome using laser speckle blood flow imaging.
Methods:
Patients with primary dysmenorrhea and cold coagulation and blood stasis syndrome (primary dysmenorrhea group, n=53) and healthy female college students(control group, n=57) who met the inclusion and exclusion criteria from October 2020 to July 2022 were enrolled at Hebei University of Chinese Medicine. On the premenstrual and first day of menstruation, a laser speckle blood flow imaging system was used to measure the microcirculation blood flow perfusion on the surface of acupoints related to the conception, thoroughfare, and governor vessels, and stomach, spleen, and bladder meridians in the abdomen and lumbosacral regions. The dynamic changes in microcirculation were calculated based on the difference in average blood flow perfusion at each acupoint before and after menstruation. Receiver operating curve (ROC) analysis was used to analyze the diagnostic efficacy of dynamic changes in microcirculation on the surface of each acupoint. The microcirculation sensitization rate of acupoints was calculated.
Results:
Compared with the control group, the dynamic changes in microcirculation at the following acupoints in the primary dysmenorrhea group were increased (P<0.05): conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]); left thoroughfare vessel (left Huangshu[KI16], left Zhongzhu[KI15], left Siman[KI14], left Qixue[KI13], left Dahe[KI12], left Henggu[KI11]); left stomach meridian (left Tianshu[ST25], left Wailing[ST26], left Qichong[ST30]); left spleen meridian (left Daheng[SP15], left Fujie[SP14]); right thoroughfare vessel (right Huangshu[KI16], right Zhongzhu[KI15], right Siman[KI14], right Qixue[KI13], right Dahe[KI12], right Henggu[KI11]); right stomach meridian (right Wailing[ST26], right Daju[ST27], right Shuidao[ST28], right Guilai[ST29], right Qichong[ST30]); and right spleen meridian (right Fujie[SP14]). The area under the ROC curve of conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]), thoroughfare vessel (right Siman[KI14], left Huangshu[KI16], right Qixue[KI13], right Zhongzhu[KI15], right Dahe[KI12], left Zhongzhu[KI15], left Siman[KI14], right Huangshu[KI16], left Qixue[KI13], right Henggu[KI11], left Henggu[KI11], left Dahe[KI12]); stomach meridian (left Tianshu[ST25], right Guilai[ST29], left Wailing[ST26], right Shuidao[ST28], right Daju[ST27], right Wailing[ST26], right Qichong[ST30], left Qichong[ST30]), and spleen meridian (left Daheng[SP15], left Fujie[SP14], right Fujie[SP14]) was 0.610-0.682 (P<0.05). Compared with the control group, the sensitization rate of some acupoints in the primary dysmenorrhea group increased (P<0.05).
Conclusion
With the onset of menstruation, the blood flow perfusion of some acupoints in the abdomen (thoroughfare, and conception vessels, and stomach and spleen meridians) of patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome increased, and the status of acupoints changed from a resting state to an active state. These acupoints are sensitive in patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome and have a certain diagnostic efficacy, providing a basis for further analyzing the efficacy and mechanism of acupuncture and moxibustion to treat primary dysmenorrhea with cold blood coagulation and blood stasis syndrome.
4.Clinicopathologic features and prognostic analysis of colonic rhabdoid carcinoma:a case report and literature review
Qilin ZHOU ; Yuqiang LI ; Linyi ZHENG ; Zui TAO ; Fengbo TAN ; Qian PEI ; Yuan ZHOU ; Haiping PEI
Chinese Journal of General Surgery 2025;34(10):2148-2158
Background and Aims:Rhabdoid carcinoma of the colon(RCC)is an exceptionally rare and highly aggressive malignancy characterized by early metastasis and poor prognosis,with no standardized treatment available.We report a case of ascending colon RCC and summarize previously published cases to improve understanding of its clinicopathologic and molecular features.Methods:The clinical data,imaging,pathology,and immunohistochemistry of one patient treated at Xiangya Hospital were retrospectively analyzed.In addition,36 published RCC cases were systematically reviewed.Clinical characteristics,tumor location,immunophenotype,molecular alterations,treatments,and survival outcomes were extracted and summarized.Results:A 71-year-old man presented with abdominal distension,pain,and altered bowel habits.Imaging and colonoscopy indicated an obstructing ascending colon mass.Laparoscopic right hemicolectomy was performed.Pathology revealed poorly differentiated RCC infiltrating the serosa with 4/21 lymph-node metastases.Immunohistochemistry showed AE1/AE3(+),vimentin(+),CDX2(-),CK20(-),and Ki-67(80%+),with retained INI1 expression.Genetic testing indicated KRAS mutation and wild-type BRAFV600E.The patient received no adjuvant therapy and died of peritoneal metastasis within 3 months.Including this case,37 RCC patients(male to female ratio=1.3∶1;mean age 66 years)have been documented.Sixty-two percent of tumors were right-sided.Most exhibited rhabdoid morphology with diffuse vimentin positivity(97.06%)and AE1/AE3 positivity(100.00%),while CDX2 was negative in 85.71%.BRAFV600E mutation was present in 65.00%,and KRAS mutation in 22.73%of tested cases.Among 28 patients with MMR data,60.71%were pMMR and 39.29%dMMR.Although surgery was the primary treatment,78.79%of patients died within 1 year(median survival 6.0 months),with only a few long-term survivors following adjuvant chemotherapy or immunotherapy.Conclusion:RCC is a rapidly progressive colorectal malignancy with extremely poor prognosis and limited response to conventional chemotherapy.Tumor dedifferentiation,INI1 deficiency,and alterations in KRAS/BRAF-MAPK signaling may contribute to its pathogenesis.Surgery remains the mainstay of treatment,but incorporation of immunotherapy,targeted agents,and radiotherapy may offer potential benefits.Further studies are urgently needed to define effective therapeutic strategies.
5.Metabolic insights into gut microbiota in the pharmacology of natural medicines.
Zixin CHEN ; Junchi ZHOU ; Xiao ZHENG ; Hao XIE ; Haiping HAO
Chinese Journal of Natural Medicines (English Ed.) 2025;23(2):158-168
Natural medicines (NMs) demonstrate distinct advantages in the clinical management of chronic diseases. Recent years have seen growing recognition of the gut microbiota's role in the efficacy and synergy of NMs, providing new impetus for elucidating the material basis and mechanisms of NMs and their path toward modernization. A fundamental question that has emerged is how NM-microbiota interactions integrate into the multi-target holistic mechanisms of NMs, the answer to which may also illuminate new avenues for drug discovery. Metabolic regulation via small-molecule metabolites has been increasingly implicated in host-microbe interaction. This review presents an integral metabolic perspective on NMs-microbiota interaction in host health and disease. It highlights the emerging understanding of gut microbiota-related metabolic signals implicated in NM components' local and systemic actions. Additionally, it discusses key issues and prospects related to drug development and the translational study of NMs.
Gastrointestinal Microbiome/drug effects*
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Humans
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Biological Products/metabolism*
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Animals
6.Consensus on informed consent for orthodontic treatment
Yang CAO ; Bing FANG ; Zuolin JIN ; Hong HE ; Yuxing BAI ; Lin WANG ; Haiping LU ; Zhihe ZHAO ; Tianmin XU ; Weiran LI ; Min HU ; Jinlin SONG ; Jun WANG ; Fang JIN ; Ding BAI ; Xianglong HAN ; Yuehua LIU ; Bin YAN ; Jie GUO ; Jiejun SHI ; Yongming LI ; Zhihua LI ; Xiuping WU ; Jiangtian HU ; Linyu XU ; Lin LIU ; Yi LIU ; Yanqin LU ; Wensheng MA ; Shuixue MO ; Liling REN ; Shuxia CUI ; Yongjie FAN ; Jianguang XU ; Lulu XU ; Zhijun ZHENG ; Peijun WANG ; Rui ZOU ; Chufeng LIU ; Lunguo XIA ; Li HU ; Weicai WANG ; Liping WU ; Xiaoxing KOU ; Jiali TAN ; Yuanbo LIU ; Bowen MENG ; Yuantao HAO ; Lili CHEN
Chinese Journal of Stomatology 2025;60(12):1327-1336
This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.
7.Clinical efficacy of staged reconstructive surgery with anterolateral thigh flap for wrist-forearm soft tissue defects of electrical burns
Junjie ZHENG ; Dayong CAO ; Gaoyuan YANG ; Kai YU ; Lei WANG ; Yan LIANG ; Guoyun DONG ; Chengde XIA ; Haiping DI
Chinese Journal of Microsurgery 2025;48(2):142-148
Objective:To explore the clinical efficacy of staged reconstruction with anterolateral thigh flap (ALTF) for wrist-forearm soft tissue defects of electrical burns.Methods:A retrospective observational study was conducted on 10 patients who had wrist-forearm soft tissue defects after electrical burns and were admitted in the Department of Burns, Zhengzhou First People's Hospital from January 2019 to December 2022. The patients were 6 males and 4 females, aged 8 to 64 years. All the patients were third-and-fourth degree electrical burns. Debridement was performed to remove the necrotic tissues around the wound in stage I surgery. Area of the wound after debridement ranged from 15 cm×11 cm to 31 cm×20 cm. According to the condition of wrist-forearm injury, the wounds with relatively mild injury were retained. Free ALTF was used to cover the wound surface. Size of the flaps ranged from 16 cm×12 cm to 32 cm×21 cm. The descending branch of lateral circumflex femoral artery and the accompanying veins carried by the flap were anastomosed end-to-end with the radial artery and vein or ulnar artery and vein in the recipient site, respectively. Conditions of other vessels were explored. The great saphenous veins in a length of 10-18 cm was used to bridge the occluded arteries. The donor sites were covered by medium thick skin grafts from trunk. After survival of the flap, stage Ⅱ surgery was carried out to debride the wound temporarily retained in stage I surgery and to thin the flap, then had all the wound covered with the thinned flap. Follow-ups were conducted at outpatient clinic, and via telephone and WeChat interviews. The limb salvage, flap survival, vascular compromise and other complications, as well as the donor site healing were observed. The wound coverage rate of the thinned flap. The appearance of flap, donor site scar hyperplasia, the patient satisfaction with the shape and function of the donor site at 6 months after the stage Ⅱ surgery were evaluated. Likert scale was employed to evaluate the patient satisfaction. The Michigan Hand Outcomes Questionnaire (MHQ) and Disabilities of the Arm, Shoulder and Hand (DASH) were used to evaluate the upper limb function in daily life of the patients.Results:The limb salvages in the 10 patients were all successful, and the flaps survived without any postoperative event of vascular compromise or other complication. One patient had mild cyanosis at the edges of flap after surgery and regressed at 7 days later. One flap had poor blood circulation and partial necrosis. The thinned flaps covered the wound completely after the stage-Ⅱ flap thinning surgery. The postoperative follow-up period was 6.0-7.0 months. All skin grafts in the donor sites survived well. The thinned flaps of stage Ⅱ surgery achieved 100% in wound coverage rate. At 6 months after surgery, the colour and texture of the flaps were about the same as those of the normal skin of the upper limb. There were linear scars in both of donor and recipient sites. Four patients were satisfactory to the postoperative appearance and function of the donor site and 6 patients were very satisfactory. MHQ scores were 49-82 (mean, 74) points; DASH scores were 27-45 (mean, 32) points.Conclusion:Reconstruction of the wounds in wrist-forearm soft tissue defects of electrical burns with ALTF in staged surgery, can improve the function and aesthetics of the wrist-forearm. It is a good method.
8.Determination of docusate sodium by ion-pair high-performance liquid chromatography
Lirong CAI ; Haiping SHU ; Sha XIAO ; Yue TAN ; Jinfeng ZHENG ; Changliang LI ; Yanming LIU
Journal of China Pharmaceutical University 2025;56(2):183-187
To reduce the dependency on high-carbon-load chromatographic columns,a new method has been established for the determination of the content of docusate sodium using ion-pair high-performance liquid chromatography(IP-HPLC).Tetrapropylammonium chloride was used as the ion-pair reagent with a mobile phase,composition of acetonitrile:10 mmol/L tetrapropylammonium chloride solution=66∶34,adjusting pH to 6.5 with 0.1%phosphoric acid solution,flow rate of 1.5 mL/min,detection wavelength of 214 nm,column temperature of 35℃,and an injection volume of 25 μL,and quantified by an external standard method.The main peak of docusate sodium exhibited a tailing factor of 1.34.The method showed good linearity within the range of 0.02 mg/mL to 0.40 mg/mL,with a correlation coefficient(r)of 0.999 9.It also demonstrated good repeatability,with recovery ranging from 97.0%to 98.2%(n=6).The quantification limit was 3.31 μg/mL,and the detection limit was 2.76 μg/mL.In summary,the new method shows good durability,a wide linear range,and high sensitivity,it is suitable for the determination of docusate sodium.
9.Autologous scalp repair of wounds in the medium-thickness skin donor area:safety and effectiveness
Dayong CAO ; Junjie ZHENG ; Lei WANG ; Yang YANG ; Haina GUO ; Peipeng XING ; Chengde XIA ; Haiping DI
Chinese Journal of Tissue Engineering Research 2025;29(18):3804-3810
BACKGROUND:Large deep burn wounds are often accompanied by scar hyperplasia after healing,requiring transplantation of medium-thickness skin for repair,and the medium-thickness skin slices taken generally reach below the papillary layer of the dermis.If not handled correctly,complications such as delayed healing,ulceration,and post-healing pain and itching in the donor area can easily occur.Therefore,the repair of wounds in the donor area should be emphasized.OBJECTIVE:To observe the safety and practicability of autologous scalp repair of skin donor area in patients with deep burns and scarring.METHODS:Sixty patients with deep burn and scar hyperplasia admitted to the Burn Department of Zhengzhou First People's Hospital from January 2021 to September 2023 were selected as the study subjects.They all needed medium-thickness skin transplantation and repair,and were divided into study group(n=30)and control group(n=30)according to random systematic sampling method.The skin was taken from the patient's own medium-thickness skin on the leg or back.In the study group,the skin donor area was repaired with self-blade thick scalp replantation,and in the control group,the skin donor area was repaired with absorbent dressing.The wound healing rate and the time to complete epithelialization of the wound were observed and compared in the two groups 6 days after surgery.The pain of dressing change at 3 and 6 days after surgery and scar hyperplasia in the skin donor area at 6 months after surgery were compared between two groups.RESULTS AND CONCLUSION:Compared with the control group,the time to complete epithelialization of the wound was significantly lower in the study group(P<0.05),and the wound healing rate was significantly higher in the study group(P<0.05),the pain score for dressing change at 3 and 6 days after surgery was significantly lower in the study group(P<0.05),and the scar hyperplasia rate,scar score and itch score were also significantly lower in the study group(P<0.05)at 6 months after surgery.In conclusion,autologous scalp repair of the medium-thickness skin donor area can accelerate wound healing and reduce scar hyperplasia.
10.Clinicopathologic features and prognostic analysis of colonic rhabdoid carcinoma:a case report and literature review
Qilin ZHOU ; Yuqiang LI ; Linyi ZHENG ; Zui TAO ; Fengbo TAN ; Qian PEI ; Yuan ZHOU ; Haiping PEI
Chinese Journal of General Surgery 2025;34(10):2148-2158
Background and Aims:Rhabdoid carcinoma of the colon(RCC)is an exceptionally rare and highly aggressive malignancy characterized by early metastasis and poor prognosis,with no standardized treatment available.We report a case of ascending colon RCC and summarize previously published cases to improve understanding of its clinicopathologic and molecular features.Methods:The clinical data,imaging,pathology,and immunohistochemistry of one patient treated at Xiangya Hospital were retrospectively analyzed.In addition,36 published RCC cases were systematically reviewed.Clinical characteristics,tumor location,immunophenotype,molecular alterations,treatments,and survival outcomes were extracted and summarized.Results:A 71-year-old man presented with abdominal distension,pain,and altered bowel habits.Imaging and colonoscopy indicated an obstructing ascending colon mass.Laparoscopic right hemicolectomy was performed.Pathology revealed poorly differentiated RCC infiltrating the serosa with 4/21 lymph-node metastases.Immunohistochemistry showed AE1/AE3(+),vimentin(+),CDX2(-),CK20(-),and Ki-67(80%+),with retained INI1 expression.Genetic testing indicated KRAS mutation and wild-type BRAFV600E.The patient received no adjuvant therapy and died of peritoneal metastasis within 3 months.Including this case,37 RCC patients(male to female ratio=1.3∶1;mean age 66 years)have been documented.Sixty-two percent of tumors were right-sided.Most exhibited rhabdoid morphology with diffuse vimentin positivity(97.06%)and AE1/AE3 positivity(100.00%),while CDX2 was negative in 85.71%.BRAFV600E mutation was present in 65.00%,and KRAS mutation in 22.73%of tested cases.Among 28 patients with MMR data,60.71%were pMMR and 39.29%dMMR.Although surgery was the primary treatment,78.79%of patients died within 1 year(median survival 6.0 months),with only a few long-term survivors following adjuvant chemotherapy or immunotherapy.Conclusion:RCC is a rapidly progressive colorectal malignancy with extremely poor prognosis and limited response to conventional chemotherapy.Tumor dedifferentiation,INI1 deficiency,and alterations in KRAS/BRAF-MAPK signaling may contribute to its pathogenesis.Surgery remains the mainstay of treatment,but incorporation of immunotherapy,targeted agents,and radiotherapy may offer potential benefits.Further studies are urgently needed to define effective therapeutic strategies.


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