OBJECTIVE To establish a preparation method for Phellodendrine-11-O-β-D-glucuronide(M1),a metabolite of Phellodendrine(PHE),and to evaluate its regulatory effects on glycolipid metabolism disorder in insulin-resistant HepG2(IR-HepG2)cells.METHODS The preparation,extraction,separation,purification and identification of M1 were completed by in vitro incuba-tion of intestinal microsomes combined with liquid phase,mass spectrometry and NMR.With Metformin as positive control,IR-HepG2 cells were treated with low(25 μmol·L-1),medium(50 μmol·L-1)and high(100 μmol·L-1)doses of M1 for 24 h.Glucose con-sumption,glucose uptake,triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)were quantified.The binding ability of M1 to the key targets INSR,IRS1,PI3K and AKT2 in the IRS1/PI3K/AKT pathway was explored through molecular docking technology.The effects of M1 on the mRNA and protein expression of these key targets in the IRS1/PI3K/AKT pathway were detected by qPCR and Western blot,respectively.RESULTS The purified product was confirmed by NMR as Phellodendrine-11-O-β-D-glucuronide(95%purity).Compared to the model group,all M1 do-ses significantly enhanced glucose consumption(P<0.01,P<0.001)and uptake(P<0.001)in IR-HepG2 cells,outperforming PHE(P<0.001).At medium and high doses,it could significantly reduce the content of TG and TC in cells(P<0.001),and its improve-ment effect at the TG level was better than that of PHE(P<0.01);while all concentrations decreased LDL-C(P<0.001)and in-creased HDL-C(P<0.01,P<0.001).Molecular docking revealed strong binding interactions between M1 and INSR,IRS1,PI3K,and AKT2.Compared with the model group,M1 administration group increased the expression of INSR,IRS1,PI3K,AKT2,and GLUT2 mRNA to varying degrees,downregulated the protein expression of p-IRS1/IRS1(P<0.001),and upregulated the protein ex-pression of PI3K,p-AKT/AKT,and p-GSK3β/GSK3β.CONCLUSION The established protocol enables high purity M1 prepara-tion.M1 alleviates IR by regulating IRS1/PI3K/AKT signaling pathway to improve the disorder of glycolipid metabolism.

Objective:To explore the impact of neoadjuvant immunotherapy on the occurrence of low anterior resection syndrome (LARS) in patients with locally advanced rectal cancer who underwent restorative anterior resection, and to analyze associated risk factors.Methods:This study was an observational study. Patients with adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma of the rectum located 0-10 cm from the anal verge who received neoadjuvant immunotherapy followed by curative restorative anterior resection at Peking University Cancer Hospital between November 2019 and February 2024 were retrospectively examined. Exclusion criteria were as follows: (1) metastasis detected preoperatively;(2) follow-up <1 year or stoma closure <6 months; (3) local recurrence or metastasis during follow-up; and (4) stoma without closure or stoma re-creation. The Chinese version of the LARS questionnaire was used to assess bowel function by telephone interview, and patients were classified based on score into no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30–42 points). The incidence of LARS, major LARS, and associated risk factors were analyzed.Results:A total of 52 patients (34 men) were included for analysis. Mean age was 58.0 ± 9.8 years and mean body mass index was 25.1 ± 2.6 kg/m 2. Median follow-up was 27.5 months (range, 12.0-63.7). Median LARS score was 21 (range, 1-41). Twenty-six patients (50.0%) developed LARS after surgery, and half of these (13 cases) were classified as major LARS. Stool clustering (repeated defecation within 1 hour) was observed in 80.8% (42/52) of patients. Distance between the tumor edge and the dentate line [odds ratio (OR), 3.597; 95% confidence interval (CI), 1.140-11.360; P=0.026], management of the left colic artery (OR, 0.133; 95% CI, 0.026-0.691; P=0.008), and interval of stoma closure (OR, 5.250; 95%CI, 1.381-19.960; P=0.011) were significantly associated with LARS. Interval of stoma closure was significantly associated with major LARS (OR, 4.200; 95%CI, 1.064–16.584; P=0.040). In multivariate logistic regression, ≤3.5 cm between the tumor edge and the dentate line (OR, 7.407; 95%CI, 1.377-40.000; P=0.020), non-preservation of the left colic artery (OR, 8.403; 95%CI, 1.183-58.823; P=0.033) and interval of stoma closure >6 months (OR, 10.865; 95% CI, 2.039-57.896; P=0.005) were independent risk factors for LARS. Interval of stoma closure >6 months (OR, 4.356; 95% CI, 1.105-17.167; P=0.035) were independent risk factors for major LARS. Conclusion:Patients with locally advanced rectal cancer treated with neoadjuvant immunotherapy experienced a high incidence of LARS after curative surgery, with stool clustering as the predominant symptom. Tumor edge–dentate line distance ≤3.5 cm, non-preservation of the left colic artery, and interval of stoma closure >6 months were risk factors for LARS.

OBJECTIVE To establish a preparation method for Phellodendrine-11-O-β-D-glucuronide(M1),a metabolite of Phellodendrine(PHE),and to evaluate its regulatory effects on glycolipid metabolism disorder in insulin-resistant HepG2(IR-HepG2)cells.METHODS The preparation,extraction,separation,purification and identification of M1 were completed by in vitro incuba-tion of intestinal microsomes combined with liquid phase,mass spectrometry and NMR.With Metformin as positive control,IR-HepG2 cells were treated with low(25 μmol·L-1),medium(50 μmol·L-1)and high(100 μmol·L-1)doses of M1 for 24 h.Glucose con-sumption,glucose uptake,triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)were quantified.The binding ability of M1 to the key targets INSR,IRS1,PI3K and AKT2 in the IRS1/PI3K/AKT pathway was explored through molecular docking technology.The effects of M1 on the mRNA and protein expression of these key targets in the IRS1/PI3K/AKT pathway were detected by qPCR and Western blot,respectively.RESULTS The purified product was confirmed by NMR as Phellodendrine-11-O-β-D-glucuronide(95%purity).Compared to the model group,all M1 do-ses significantly enhanced glucose consumption(P<0.01,P<0.001)and uptake(P<0.001)in IR-HepG2 cells,outperforming PHE(P<0.001).At medium and high doses,it could significantly reduce the content of TG and TC in cells(P<0.001),and its improve-ment effect at the TG level was better than that of PHE(P<0.01);while all concentrations decreased LDL-C(P<0.001)and in-creased HDL-C(P<0.01,P<0.001).Molecular docking revealed strong binding interactions between M1 and INSR,IRS1,PI3K,and AKT2.Compared with the model group,M1 administration group increased the expression of INSR,IRS1,PI3K,AKT2,and GLUT2 mRNA to varying degrees,downregulated the protein expression of p-IRS1/IRS1(P<0.001),and upregulated the protein ex-pression of PI3K,p-AKT/AKT,and p-GSK3β/GSK3β.CONCLUSION The established protocol enables high purity M1 prepara-tion.M1 alleviates IR by regulating IRS1/PI3K/AKT signaling pathway to improve the disorder of glycolipid metabolism.

Objective:To explore the impact of neoadjuvant immunotherapy on the occurrence of low anterior resection syndrome (LARS) in patients with locally advanced rectal cancer who underwent restorative anterior resection, and to analyze associated risk factors.Methods:This study was an observational study. Patients with adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma of the rectum located 0-10 cm from the anal verge who received neoadjuvant immunotherapy followed by curative restorative anterior resection at Peking University Cancer Hospital between November 2019 and February 2024 were retrospectively examined. Exclusion criteria were as follows: (1) metastasis detected preoperatively;(2) follow-up <1 year or stoma closure <6 months; (3) local recurrence or metastasis during follow-up; and (4) stoma without closure or stoma re-creation. The Chinese version of the LARS questionnaire was used to assess bowel function by telephone interview, and patients were classified based on score into no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30–42 points). The incidence of LARS, major LARS, and associated risk factors were analyzed.Results:A total of 52 patients (34 men) were included for analysis. Mean age was 58.0 ± 9.8 years and mean body mass index was 25.1 ± 2.6 kg/m 2. Median follow-up was 27.5 months (range, 12.0-63.7). Median LARS score was 21 (range, 1-41). Twenty-six patients (50.0%) developed LARS after surgery, and half of these (13 cases) were classified as major LARS. Stool clustering (repeated defecation within 1 hour) was observed in 80.8% (42/52) of patients. Distance between the tumor edge and the dentate line [odds ratio (OR), 3.597; 95% confidence interval (CI), 1.140-11.360; P=0.026], management of the left colic artery (OR, 0.133; 95% CI, 0.026-0.691; P=0.008), and interval of stoma closure (OR, 5.250; 95%CI, 1.381-19.960; P=0.011) were significantly associated with LARS. Interval of stoma closure was significantly associated with major LARS (OR, 4.200; 95%CI, 1.064–16.584; P=0.040). In multivariate logistic regression, ≤3.5 cm between the tumor edge and the dentate line (OR, 7.407; 95%CI, 1.377-40.000; P=0.020), non-preservation of the left colic artery (OR, 8.403; 95%CI, 1.183-58.823; P=0.033) and interval of stoma closure >6 months (OR, 10.865; 95% CI, 2.039-57.896; P=0.005) were independent risk factors for LARS. Interval of stoma closure >6 months (OR, 4.356; 95% CI, 1.105-17.167; P=0.035) were independent risk factors for major LARS. Conclusion:Patients with locally advanced rectal cancer treated with neoadjuvant immunotherapy experienced a high incidence of LARS after curative surgery, with stool clustering as the predominant symptom. Tumor edge–dentate line distance ≤3.5 cm, non-preservation of the left colic artery, and interval of stoma closure >6 months were risk factors for LARS.

Objective:To investigate perspectives and changes in treatment selection by Chinese surgeons since introduction of the watch-and-wait approach after neoadjuvant therapy for rectal cancer.Methods:A cross-sectional survey was conducted using a questionnaire distributed through the "Wenjuanxing" online survey platform. The survey focused on the recognition and practices of Chinese surgeons regarding the strategy of watch-and-wait after neoadjuvant therapy for rectal cancer and was disseminated within the China Watch-and-Wait Database (CWWD) WeChat group. This group targets surgeons of deputy chief physician level and above in surgical, radiotherapy, or internal medicine departments of nationally accredited tumor-specialist or comprehensive hospitals (at provincial or municipal levels) who are involved in colorectal cancer diagnosis and treatment. From 13 to 16 December 2023, 321 questionnaires were sent with questionnaire links in the CWWD WeChat group. The questionnaires comprised 32 questions encompassing: (1) basic physician characteristics (including surgical volume); (2) assessment methods and criteria for clinical complete response (cCR); (3) patients eligible for watch-and-wait; (4) neoadjuvant therapies and other measures for achieving cCR; (5) willingness to implement watch-and-wait and factors influencing that willingness; (6) risks and monitoring of watch-and-wait; (7) subsequent treatment and follow-up post watch-and-wait; (8) suggestions for development of the CWWD. Descriptive statistics were employed for data analysis, with intergroup comparisons conducted using the χ 2 or Fisher's exact probability tests. Results:The response rate was 31.5%, comprising 101 responses from the 321 individuals in the WeChat group. Respondents comprised 101 physicians from 70 centers across 23 provinces, municipalities, and autonomous regions nationwide, 85.1% (86/101) of whom represented provincial tertiary hospitals. Among the respondents, 87.1% (88/101) had implemented the watch-and-wait strategy. The approval rate (65.6%, 21/32) and proportion of patients often informed (68.8%, 22/32) were both significantly higher for doctors in oncology hospitals than for those in general hospitals (27.7%, 18/65; 32.4%, 22/68) (χ 2=12.83, P<0.001; χ 2=11.70, P=0.001, respectively). The most used methods for diagnosing cCR were digital rectal examination (90.1%, 91/101), colonoscopy (91.1%, 92/101), and rectal T2-weighted magnetic resonance imaging (86.1%, 87/101). Criteria used to identify cCR comprised absence of a palpable mass on digital rectal examination (87.1%, 88/101), flat white scars or new capillaries on colonoscopy (77.2%, 78/101), absence of evident tumor signals on rectal T2-weighted sequences or T2WI low signals or signals equivalent to the intestinal wall (83.2%, 84/101), and absence of tumor hyperintensity on diffusion-weighted imaging with no corresponding hypointensity on apparent diffusion coefficient maps (66.3%, 67/101). As for selection of neoadjuvant regimen and assessment of cCR, 57.4% (58/101) of physicians preferred a long course of radiotherapy with or without induction and/or consolidation capecitabine + oxaliplatin, whereas 25.7% (26/101) preferred immunotherapy in combination with chemotherapy and concurrent radiotherapy. Most (96.0%, 97/101) physicians believed that the primary lesion should be assessed ≤12 weeks after completion of radiotherapy. Patients were frequently informed about the possibility of achieving cCR after neoadjuvant therapy and the strategy of watch-and-wait by 43.6% (44/101) of the responding physicians and 38.6% (39/101) preferred watch-and-wait for patients who achieved cCR or near cCR after neoadjuvant therapy for rectal cancer. Capability for multiple follow-up evaluations (70.3%, 71/101) was a crucial factor influencing physicians' choice of watch-and-wait after cCR. The proportion who patients who did not achieve cCR and underwent surgical treatment was lower in provincial tertiary hospitals (74.2%, 23/31) than in provincial general hospitals (94.5%, 52/55) and municipal hospitals (12/15); these differences are statistically significant (χ 2=7.43, P=0.020). The difference between local recurrence and local regrowth was understood by 88.1% (89/101) of respondents and 87.2% (88/101) agreed with monitoring every 3 months for 5 years. An increase in local excision or puncture rates to reduce organ resections in patients with pCR was proposed by 64.4% (65/101) of respondents. Conclusion:Compared with the results of a previous survey, Chinese surgeons' awareness of the watch-and-wait concept has improved significantly. Oncologists in oncology hospitals are more aware of the concept of watch-and-wait.

Objective:To investigate perspectives and changes in treatment selection by Chinese surgeons since introduction of the watch-and-wait approach after neoadjuvant therapy for rectal cancer.Methods:A cross-sectional survey was conducted using a questionnaire distributed through the "Wenjuanxing" online survey platform. The survey focused on the recognition and practices of Chinese surgeons regarding the strategy of watch-and-wait after neoadjuvant therapy for rectal cancer and was disseminated within the China Watch-and-Wait Database (CWWD) WeChat group. This group targets surgeons of deputy chief physician level and above in surgical, radiotherapy, or internal medicine departments of nationally accredited tumor-specialist or comprehensive hospitals (at provincial or municipal levels) who are involved in colorectal cancer diagnosis and treatment. From 13 to 16 December 2023, 321 questionnaires were sent with questionnaire links in the CWWD WeChat group. The questionnaires comprised 32 questions encompassing: (1) basic physician characteristics (including surgical volume); (2) assessment methods and criteria for clinical complete response (cCR); (3) patients eligible for watch-and-wait; (4) neoadjuvant therapies and other measures for achieving cCR; (5) willingness to implement watch-and-wait and factors influencing that willingness; (6) risks and monitoring of watch-and-wait; (7) subsequent treatment and follow-up post watch-and-wait; (8) suggestions for development of the CWWD. Descriptive statistics were employed for data analysis, with intergroup comparisons conducted using the χ 2 or Fisher's exact probability tests. Results:The response rate was 31.5%, comprising 101 responses from the 321 individuals in the WeChat group. Respondents comprised 101 physicians from 70 centers across 23 provinces, municipalities, and autonomous regions nationwide, 85.1% (86/101) of whom represented provincial tertiary hospitals. Among the respondents, 87.1% (88/101) had implemented the watch-and-wait strategy. The approval rate (65.6%, 21/32) and proportion of patients often informed (68.8%, 22/32) were both significantly higher for doctors in oncology hospitals than for those in general hospitals (27.7%, 18/65; 32.4%, 22/68) (χ 2=12.83, P<0.001; χ 2=11.70, P=0.001, respectively). The most used methods for diagnosing cCR were digital rectal examination (90.1%, 91/101), colonoscopy (91.1%, 92/101), and rectal T2-weighted magnetic resonance imaging (86.1%, 87/101). Criteria used to identify cCR comprised absence of a palpable mass on digital rectal examination (87.1%, 88/101), flat white scars or new capillaries on colonoscopy (77.2%, 78/101), absence of evident tumor signals on rectal T2-weighted sequences or T2WI low signals or signals equivalent to the intestinal wall (83.2%, 84/101), and absence of tumor hyperintensity on diffusion-weighted imaging with no corresponding hypointensity on apparent diffusion coefficient maps (66.3%, 67/101). As for selection of neoadjuvant regimen and assessment of cCR, 57.4% (58/101) of physicians preferred a long course of radiotherapy with or without induction and/or consolidation capecitabine + oxaliplatin, whereas 25.7% (26/101) preferred immunotherapy in combination with chemotherapy and concurrent radiotherapy. Most (96.0%, 97/101) physicians believed that the primary lesion should be assessed ≤12 weeks after completion of radiotherapy. Patients were frequently informed about the possibility of achieving cCR after neoadjuvant therapy and the strategy of watch-and-wait by 43.6% (44/101) of the responding physicians and 38.6% (39/101) preferred watch-and-wait for patients who achieved cCR or near cCR after neoadjuvant therapy for rectal cancer. Capability for multiple follow-up evaluations (70.3%, 71/101) was a crucial factor influencing physicians' choice of watch-and-wait after cCR. The proportion who patients who did not achieve cCR and underwent surgical treatment was lower in provincial tertiary hospitals (74.2%, 23/31) than in provincial general hospitals (94.5%, 52/55) and municipal hospitals (12/15); these differences are statistically significant (χ 2=7.43, P=0.020). The difference between local recurrence and local regrowth was understood by 88.1% (89/101) of respondents and 87.2% (88/101) agreed with monitoring every 3 months for 5 years. An increase in local excision or puncture rates to reduce organ resections in patients with pCR was proposed by 64.4% (65/101) of respondents. Conclusion:Compared with the results of a previous survey, Chinese surgeons' awareness of the watch-and-wait concept has improved significantly. Oncologists in oncology hospitals are more aware of the concept of watch-and-wait.

Objective:To investigate the application of virtual simulation-based teaching-examination linkage mode based on aneSIM anesthesia simulation system and NW13 difficult airway management model in improving the ability of anesthesia crisis resource management among trainees receiving standardized residency training.Methods:A total of 236 trainees (189 trainees with non-anesthesia majors and 47 with anesthesia majors) who received standardized residency training in Department of Anesthesiology in 2021 were selected as control group, and 234 resident trainees (184 trainees with non-anesthesia majors and 50 with anesthesia majors) in 2022 were selected as observation group. The trainees in the control group received traditional theoretical teaching, and those in the observation group received teaching with the aneSIM system. The trainees in both groups received two sessions of online theoretical assessment through the QR code in Bangboss Application, as well as situational simulation training and assessment using the NW13 difficult airway management model. SPSS 26.0 was used to perform the t-test and the chi-square test. Results:Compared with the control group, the observation group had a significantly higher score of the second theoretical assessment, significantly better degree of anxiety and score of simulation assessment, and significantly better knowledge mastery and ability improvement ( t=7.15, 14.31, 3.90, 6.22, 4.23, 3.04, all P<0.05). Compared with the control group in terms of the resident trainees with non-anesthesia majors, the observation group had a significantly higher score of the second theoretical assessment, significantly better degree of anxiety and score of simulation assessment, a significantly higher degree of satisfaction with teaching, and significantly better knowledge mastery and ability improvement ( t=7.77, 5.43, 3.09, 5.26, 3.82, 2.19, all P<0.05). Compared with the control group in terms of the resident trainees with anesthesia majors, the observation group had a significantly higher score of simulation assessment, a significantly higher degree of satisfaction with teaching, and significantly better knowledge mastery and ability improvement ( t=2.60, 3.56, 2.01, 2.48, P=0.011, 0.001, 0.047, 0.015). Conclusions:The mode of virtual simulation-based teaching-examination linkage based on the aneSIM anesthesia simulation system and NW13 difficult airway management model can examine and improve the abilities for difficult airway management and operation among resident trainees, especially those with non-anesthesia majors, thereby showing its application value in the teaching of anesthesia crisis resource management.

Objective:To investigate the application of virtual simulation-based teaching-examination linkage mode based on aneSIM anesthesia simulation system and NW13 difficult airway management model in improving the ability of anesthesia crisis resource management among trainees receiving standardized residency training.Methods:A total of 236 trainees (189 trainees with non-anesthesia majors and 47 with anesthesia majors) who received standardized residency training in Department of Anesthesiology in 2021 were selected as control group, and 234 resident trainees (184 trainees with non-anesthesia majors and 50 with anesthesia majors) in 2022 were selected as observation group. The trainees in the control group received traditional theoretical teaching, and those in the observation group received teaching with the aneSIM system. The trainees in both groups received two sessions of online theoretical assessment through the QR code in Bangboss Application, as well as situational simulation training and assessment using the NW13 difficult airway management model. SPSS 26.0 was used to perform the t-test and the chi-square test. Results:Compared with the control group, the observation group had a significantly higher score of the second theoretical assessment, significantly better degree of anxiety and score of simulation assessment, and significantly better knowledge mastery and ability improvement ( t=7.15, 14.31, 3.90, 6.22, 4.23, 3.04, all P<0.05). Compared with the control group in terms of the resident trainees with non-anesthesia majors, the observation group had a significantly higher score of the second theoretical assessment, significantly better degree of anxiety and score of simulation assessment, a significantly higher degree of satisfaction with teaching, and significantly better knowledge mastery and ability improvement ( t=7.77, 5.43, 3.09, 5.26, 3.82, 2.19, all P<0.05). Compared with the control group in terms of the resident trainees with anesthesia majors, the observation group had a significantly higher score of simulation assessment, a significantly higher degree of satisfaction with teaching, and significantly better knowledge mastery and ability improvement ( t=2.60, 3.56, 2.01, 2.48, P=0.011, 0.001, 0.047, 0.015). Conclusions:The mode of virtual simulation-based teaching-examination linkage based on the aneSIM anesthesia simulation system and NW13 difficult airway management model can examine and improve the abilities for difficult airway management and operation among resident trainees, especially those with non-anesthesia majors, thereby showing its application value in the teaching of anesthesia crisis resource management.

Objective:To investigate the effects of a Baqia Huaihua Liangxue decoction on peripheral blood T helper 17 cells/Tregulatory cells(Th17/Treg)balance and the expression of related cytokines in elderly patients with psoriasis.Methods:A total of 124 elderly patients diagnosed with psoriasis and receiving treatment at our hospital from September 2018 to December 2019 were divided into the observation group and the control group according to the parity number table, with 62 cases in each group.All patients underwent conventional treatment and physical therapy, and, in addition, the observation group was treated with a Baqia Huaihua Liangxue decoction for 2 months.The blood indexes including levels of Th17, Treg, Th17/Treg, and Th17/Treg-related cytokines such as interleukin-17(IL-17), IL-22 and IL-23 in the two groups were measured before treatment and 2 months after treatment.The psoriasis area and severity index(PASI)was used to evaluate the severity of skin damage in the two groups.The traditional Chinese medicine(TCM)syndrome scores were evaluated and compared between the two groups.Adverse reactions during treatment were monitored and recorded.Results:After 2 months of treatment, the Th17 and Th17/Treg levels were lower[(1.0±0.1)% vs.(2.4±0.9)%, 0.2±0.1 vs.0.6±0.2, all P<0.05]and Treg levels were higher in the observation group than in the control group[(5.3±1.1)% vs.(4.3±1.0)%, P<0.05]. Levels of IL-17, IL-22 and IL-23 were lower in the observation group than in the control group after 2 months of treatment[(22.1±3.5)ng/L vs.(35.6±4.0)ng/L, (44.8±4.4)ng/L vs.(49.9±5.1)ng/L, (43.7±5.2)ng/L vs.(52.5±5.4)ng/L, all P<0.05]. The PASI score and TCM syndrome score were lower in the observation group than in the control group after 2 months of treatment[(2.9±1.0) vs.(6.1±2.3), (3.2±1.9) vs.(7.6±2.1), all P<0.05]. No adverse reaction occurred in the two groups during treatment. Conclusions:The Baqia Huaihua Liangxue decoction has a clear therapeutic effect in elderly patients with psoriasis.It can stabilize peripheral blood Th17/Treg balance, inhibit the expression of related cytokines, reduce the degree of skin damage and has no adverse reaction during treatment.

Objective:To explore the improvement effect of rhein lysinate (RHL)on the insulin resistance in the KK/HlJ diabetes mellitus (DM ) mice induced by streptozotocin (STZ ), and to elucidate its mechanism. Methods:The KK/HlJ diabetic mouse models were made by intraperitoneal injection of STZ (50 mg· kg-1 )and fed with DM diet.A total of 48 mice were divided into normal control group,model group,low dose of RHL group (25 mg·kg-1 )and high dose of RHL group (50 mg·kg-1 ) (n= 12).All the mice were treated for 16 weeks. The levels of fasting glucose (FBG),total cholesterol (TC)and triglyceride (TG)of the mice were measured by glucose oxidase method.HE staining was used to observe the morphology of pancreas tissue of the mice.The insulin level in pancreas islet tissue was detected by immunohistochemistry method.The levels of insulin and of C reactive protein (CRP)in serum and tumor necrosis factorα(TNF-α)and interleukin 6 (IL-6)in liver tissue of the mice were detected by enzyme linked immunosorbent assay (ELISA)method.The expression levels of glycogen synthesis related genes (PI3K,AKT and GSK-3β)phosphorylation were detected by Western blotting method. Results:Compared with model group,the levels of FBG,TG and TC of the mice in low and high doses of RHL groups were significantly decreased (P < 0.05),but there was no significant difference in the insulin level (P >0.05).Compared with model group,the levels of CRP in serum and the levels of TNF-αand IL-6 in liver tissue of the mice in low and high doses of RHL groups were significantly decreased (P <0.01).The HE staining results showed that compared with model group,the islet morphology of the mice in low and high doses of RHL groups was partially restored,and the occasional inflammatory infiltration was observed.The immunohistochemical staining results showed that compared with model group,the brown granular substance in the islets of the mice in low dose of RHL group was significantly reduced,which was disappeared in high dose of RHL group.Compared with model group,the expression levels of glycogen synthesis related genes (PI3K,AKT and GST-3β)phosphorylation of the mice in low and high doses of RHL groups were increased (P <0.01).Conclusion:RHL has improvement effect on the insulin resistance in the KK/HlJ DM mice induced by STZ,and the mechanism may be related to promoting the glycogen synthesis.