1.Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells.
Yingying WANG ; Youping ZHANG ; Hao LUO ; Wei WEI ; Wanting LIU ; Weiwei WANG ; Yunzhao WU ; Cheng PENG ; Yanjie JI ; Jianfang ZHANG ; Chujiao ZHU ; Wenhui BAI ; Li XIA ; Hu LEI ; Hanzhang XU ; Leimiao YIN ; Wei WENG ; Li YANG ; Ligen LIU ; Aiwu ZHOU ; Yueyue WEI ; Qi ZHU ; Weiliang ZHU ; Yongqing YANG ; Zhijian XU ; Yingli WU
Acta Pharmaceutica Sinica B 2024;14(12):5235-5248
Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.
2.Current status and progress in the treatment of Stanford type B aortic dissections
Chinese Journal of Primary Medicine and Pharmacy 2024;31(6):957-960
Aortic dissection is a common acute aortic syndrome. Its incidence and detection rate have been increasing in recent years, and it has received clinical attention. The treatment of aortic dissection is primarily based on the morphological characteristics and complications of the lesion. The main treatment methods include drug conservative treatment, open surgery, and intracavitary interventional therapy. With the continuous development of endovascular treatment technology and instruments, hybrid technology, windowing technology, chimney technology, branch technology, and other derivative technologies have emerged. This paper reviews the current status and progress of the treatment of Stanford type B aortic dissection, and provides a reference for clinical surgical selection.
3.Liver injury induced by Panlongqi tablets (盘龙七片)
Zhiyu XU ; Zhiheng DONG ; Aiwu ZHANG
Adverse Drug Reactions Journal 2024;26(8):504-506
A 67-year-old female patient was treated with oral 4 Panlongqi tablets thrice daily for strain of lumbar muscles. The patient developed nausea and poor appetite after 3 days of administration, followed by discharging strong brown urine and clay-colored stools. After 15 days of using the drug, she developed yellow staining of the skin and sclera, and itching appeared throughout the body. Laboratory tests showed alanine aminotransferase (ALT) 304 U/L, aspartate aminotransferase (AST) 168 U/L, alkaline phosphatase (ALP) 463.6 U/L, gamma glutamyltransferase (GGT) 1 332.3 U/L, total bilirubin (TBil) 110.5 μmol/L, and direct bilirubin (DBil) 92.3 μmol/L. After excluding viral hepatitis and biliary obstruction, drug-induced liver injury was diagnosed. Panlongqi tablets were stopped, and magnesium isoglycyrrhizinate, polyene phosphatidylcholine, ursodeoxycholic acid, and methylprednisolone were given. The patient′s discomfort symptoms were gradually eased and liver function was gradually improved. After 14 days of treatments, percutaneous liver biopsy under color doppler ultrasound was performed, and she was diagnosed as acute cholestatic hepatitis with mild fibrosis in the portal area, possibly caused by drug. After 16 days of treatments, the medication was switched to oral hepatoprotective drugs for 2 weeks. One week after stopping treatments, the patient had no discomfort and the color of skin and sclera was normal. The liver function was normal, showing ALT 31 U/L, AST 25 U/L, ALP 83.9 U/L, GGT 37.0 U/L, TBil 19.8 μmol/L, and DBil 7.3 μmol/L.
4.Liver injury induced by Panlongqi tablets (盘龙七片)
Zhiyu XU ; Zhiheng DONG ; Aiwu ZHANG
Adverse Drug Reactions Journal 2024;26(8):504-506
A 67-year-old female patient was treated with oral 4 Panlongqi tablets thrice daily for strain of lumbar muscles. The patient developed nausea and poor appetite after 3 days of administration, followed by discharging strong brown urine and clay-colored stools. After 15 days of using the drug, she developed yellow staining of the skin and sclera, and itching appeared throughout the body. Laboratory tests showed alanine aminotransferase (ALT) 304 U/L, aspartate aminotransferase (AST) 168 U/L, alkaline phosphatase (ALP) 463.6 U/L, gamma glutamyltransferase (GGT) 1 332.3 U/L, total bilirubin (TBil) 110.5 μmol/L, and direct bilirubin (DBil) 92.3 μmol/L. After excluding viral hepatitis and biliary obstruction, drug-induced liver injury was diagnosed. Panlongqi tablets were stopped, and magnesium isoglycyrrhizinate, polyene phosphatidylcholine, ursodeoxycholic acid, and methylprednisolone were given. The patient′s discomfort symptoms were gradually eased and liver function was gradually improved. After 14 days of treatments, percutaneous liver biopsy under color doppler ultrasound was performed, and she was diagnosed as acute cholestatic hepatitis with mild fibrosis in the portal area, possibly caused by drug. After 16 days of treatments, the medication was switched to oral hepatoprotective drugs for 2 weeks. One week after stopping treatments, the patient had no discomfort and the color of skin and sclera was normal. The liver function was normal, showing ALT 31 U/L, AST 25 U/L, ALP 83.9 U/L, GGT 37.0 U/L, TBil 19.8 μmol/L, and DBil 7.3 μmol/L.
5.Liver injury induced by Mugua pills(木瓜丸) combined with Zhuifeng Tougu pills (追风透骨丸)
Adverse Drug Reactions Journal 2022;24(4):223-224
A 63-year-old female patient was treated with 30 Mugua pills and Zhuifeng Tougu pills 6 g twice daily for tenosynovitis. After taking the medicine for 10 days, the patient developed nausea and vomiting, which were aggravated gradually; after taking the medicine for 22 days, the patient had fever, nausea, retching, slight pain in the upper abdomen, systemic edema, skin pruritus, and poor spirit, appetite, and sleep. Laboratory tests showed alanine aminotransferase (ALT) 454 U/L, aspartate aminotransferase (AST) 946 U/L, alkaline phosphatase (ALP) 133 U/L, gamma glutamyltransferase (γ-GT) 170 U/L, direct bilirubin (DBil) 12.8 μmol/L, and glutamate dehydrogenase 17.3 U/L. Viral hepatitis and biliary obstruction were excluded by laboratory tests and imaging examination. Drug-induced liver injury was diagnosed, Mugua pills and Zhuifeng Tougu pills were stopped, and diisopropylamine dichloroacetate injection and compound glycyrrhizin tablets were given. Liver function was gradually improved in the patient and laboratory tests showed ALT 62 U/L, AST 49 U/L, γ-GT 38 U/L, and DBil 7.2 μmol/L 12 days later. The medication was adjusted to 3 compound glycyrrhizin tablets thrice daily for 2 weeks. After 4 weeks, laboratory tests showed ALT 31 U/L, AST 26 U/L, γ-GT 30 U/L, and DBil 5.0 μmol/L.
6.Research progress on influencing factors and intervention of post-traumatic growth in maintenance hemodialysis patients
Fen ZHANG ; Ping LI ; Wei JIANG ; Aiwu YE ; Lingchang YU ; Yao LEI
Chinese Journal of Modern Nursing 2022;28(34):4852-4856
Maintenance hemodialysis can improve many symptoms of patients with end-stage renal disease, but long-term dialysis can cause various physiological symptoms and psychological negative emotions. As a positive psychological change, post-traumatic growth plays a role in relieving patients' psychological pressure and reducing their pain. However, the post-traumatic growth of patients with maintenance hemodialysis needs to be improved. This article reviewed the status, influencing factors and interventions of post-traumatic growth in maintenance hemodialysis patients in order to provide reference for psychological care of such patients.
7.Effect of Yangxue Rougan pills on the TGF-β1/Smad signaling pathway in a rat model of liver fibrosis induced by multiple factors
Yan CHAI ; Tao ZHANG ; Yinke FAN ; Aiwu HUI ; Lintao ZHAO ; Fang LI ; Xiaoli ZHANG
Journal of Clinical Hepatology 2022;38(9):2040-2045
Objective To investigate the effect of Yangxue Rougan pills on a rat model of liver fibrosis induced by multiple factors and the mechanism of action of Yangxue Rougan pills in the treatment of liver fibrosis. Methods A total of 50 male rats were randomly divided into blank control group, multi-factor model group, Fuzheng Huayu capsule group, and high-, middle-, and low-dose Yangxue Rougan pill groups. The rats in the blank control group were given normal water and feed, and those in the other groups were given modified high-fat low-protein diet and 5% alcohol, as well as subcutaneous injection of olive oil solution containing 40% carbon tetrachloride and intraperitoneal injection of pig serum 0.5 mL per rat, twice a week for 12 consecutive weeks. Since week 7, the rats in the high-, middle-, and low-dose Yangxue Rougan pill groups were given Yangxue Rougan pills at a dose of 9.5, 4.75, and 2.38 g/kg, respectively, those in the Fuzheng Huayu capsule group were given Fuzheng Huayu capsules at a dose of 0.75 g/kg, and those in the blank control group and the multi-factor model group were given an equal volume of distilled water by gavage every day for 6 consecutive weeks. The rats were treated at week 12. HE staining and Masson staining were used to observe the degree of liver fibrosis in rats, and PCR and Western blot were used to measure the expression of TGF-β1, Smad3, and Smad7 in the liver. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Dunnett's t -test was used for further comparison between two groups. Results Compared with the blank control group, the multi-factor model group had a severely damaged lobular structure and a significantly higher degree of liver fibrosis, with the formation of pseudolobules with different sizes; compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant improvement in the degree of liver fibrosis, with the most significant therapeutic effect in the high- and middle-dose Yangxue Rougan pill groups. Compared with the blank control group, the multi-factor model group had significant increases in the expression of TGF-β1 and Smad3 and a significant reduction in the expression of Smad7 in liver tissue (all P < 0.05); compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant reduction in the expression of TGF-β1 and a significant increase in the expression of Smad7 (all P < 0.05); compared with the multi-factor model group, the high- and middle-dose Yangxue Rougan pill groups had a significant reduction in the expression of Smad3 (both P < 0.05). Conclusion Yangxue Rougan pills can significantly inhibit liver fibrosis in rats by downregulating the expression of TGF-β1 and Smad3 and upregulating the expression of Smad7, and therefore, the TGF-β1/Smad signaling pathway is one of the mechanisms of action of Yangxue Rougan pills in improving liver fibrosis.
8.Liver injury induced by Mugua pills(木瓜丸) combined with Zhuifeng Tougu pills (追风透骨丸)
Adverse Drug Reactions Journal 2022;24(4):223-224
A 63-year-old female patient was treated with 30 Mugua pills and Zhuifeng Tougu pills 6 g twice daily for tenosynovitis. After taking the medicine for 10 days, the patient developed nausea and vomiting, which were aggravated gradually; after taking the medicine for 22 days, the patient had fever, nausea, retching, slight pain in the upper abdomen, systemic edema, skin pruritus, and poor spirit, appetite, and sleep. Laboratory tests showed alanine aminotransferase (ALT) 454 U/L, aspartate aminotransferase (AST) 946 U/L, alkaline phosphatase (ALP) 133 U/L, gamma glutamyltransferase (γ-GT) 170 U/L, direct bilirubin (DBil) 12.8 μmol/L, and glutamate dehydrogenase 17.3 U/L. Viral hepatitis and biliary obstruction were excluded by laboratory tests and imaging examination. Drug-induced liver injury was diagnosed, Mugua pills and Zhuifeng Tougu pills were stopped, and diisopropylamine dichloroacetate injection and compound glycyrrhizin tablets were given. Liver function was gradually improved in the patient and laboratory tests showed ALT 62 U/L, AST 49 U/L, γ-GT 38 U/L, and DBil 7.2 μmol/L 12 days later. The medication was adjusted to 3 compound glycyrrhizin tablets thrice daily for 2 weeks. After 4 weeks, laboratory tests showed ALT 31 U/L, AST 26 U/L, γ-GT 30 U/L, and DBil 5.0 μmol/L.
9.Liver injury induced by Jingangteng capsules (金刚藤胶囊) combined with Kangfuyan capsules (康妇炎胶囊)
Adverse Drug Reactions Journal 2021;23(5):273-274
A 46-year-old female patient was treated with Jingangteng capsules 2 g (4 capsules) thrice daily and Kangfuyan capsules 1.2 g (3 capsules) twice daily after hysterectomy. After 23 days of treatments, the patient developed gastrointestinal discomfort, and Jingangteng capsules and Kangfuyan capsules were stopped 2 days later. However, gastrointestinal discomfort gradually worsened and symptoms such as nausea, dark urine, and yellow staining of the skin and sclera appeared. After discontinuing the drug for 10 days, laboratory tests showed alanine aminotransferase (ALT) 366 U/L, aspartate aminotransferase (AST) 485 U/L, alkaline phosphatase (ALP) 145 U/L, gamma glutamyltransferase (γ-GT) 67 U/L, total bilirubin (TBil) 67.1 μmol/L, and direct bilirubin (DBil) 59.5 μmol/L. Viral hepatitis and biliary obstruction were excluded by laboratory tests and imaging examination, and drug-induced liver injury was diagnosed. Oral liver-protective drugs and IV infusions of compound glycyrrhizin injection and polyene phosphatidylcholine injection were given successively, but jaundice continued to deepen with the peak TBil and DBil values of 189.7 μ mol/L and 159.4 μ mol/L, respectively. An IV infusion of ademetionine 1,4-butanedisulfonate for injection 1 g dissolved in 5% glucose injection 250 ml was given once daily. Three days later, the patient′s symptoms were improved and the jaundice subsided obviously; 9 days later, the liver function was improved obviously and laboratory tests showed ALT 29 U/L, AST 50 U/L, γ-GT 36 U/L, TBil 66.5 μmol/L, and DBil 53.2 μmol/L; 1 month later, her liver function returned to normal.
10.Clinical research of laparoscopic assisted removal of greater omentum free transplantation combined with skin grafting for the repair of large area refractory wounds
Xiaofeng ZHANG ; Aiwu WANG ; Guiru YAN ; Gang HU ; Xudong CHEN ; Qinghua XU ; Juhui ZHAO ; Hong WANG ; Liliang ZHAO
Chinese Journal of Plastic Surgery 2021;37(2):187-191
Objective:To investigate the clinical effect of laparoscopic assisted removal of greater omentum free transplantation combined with skin grafting for the repair of large area refractory wounds.Methods:From June 2013 to June 2018, 18 cases of lower extremity skin and soft tissue defects with multiple bone, joint, tendon and internal plants exposure were admitted to Hanzhong Central Hospital, including 12 males and 6 females, aged from 15 to 50 years old, with an average age of 32.6 years old. The area of skin and soft tissue defect: 30 cm×12 cm-53 cm×21 cm. The operation was divided into two stages. In the first stage, the greater omentum was acquired with the assist of laparoscope and free transplanted to cover the wound. After the greater omentum free transplantation was confirmed to survive, the split-thickness skin graft was applied for wound repair.Postoperative survival of the greater omentum and skin grafting, complications, appearance and function of lower limbs were observed and followed up.Results:The 18 operations were performed successfully, the area of omentum resection was 25 cm×10 cm-35 cm×15 cm, all the greater omentums survived after operation without complications such as intestinal adhesion, volvulus and peritonitis. The area of the skin grafting was 36 cm×8 cm-45 cm×22 cm. 16 cases skin grafting survived completely, 2 cases skin grafting were necrosis just local small area, and scar healed after dressing change. Postoperative follow-up of 6-12 months showed good appearance and function of lower limbs and satisfactory results.Conclusions:For the large area soft tissue defect wound of lower extremity, complicated with multiple deep tissues such as bone, joint and internal materials exposed, the greater omentum free transplantation under laparoscope combined with medium thick skin graft second stage has the advantages of good appearance and function after wound healing, less donor injury and fewer postoperative complications.

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