Objective To study anti-inflammatory activities of oridonin derivatives without Michael fragment. Methods Two oridonin sulfonylureas were designed and synthesized by a photocatalysis reaction and a scaffold hopping strategy. The inhibitory rate of IL-1β was selected for anti-inflammatory activity evaluation. Results Both compound ZM658 and ZM659 revealed potent anti-inflammatory activities with the values of 69.3% and 59.7% in THP-1 cells, respectively. Moreover, two compounds also showed dose-dependent and low cytotoxicity. Conclusion The result indicated that Michael receptor fragment of oridonin could be substituted with sulfonylurea group.

Objective To study the antitumor activities of RRx-001 derivatives with novel covalent fragments. Methods Four targeted compounds were designed and synthesized. The structures were confirmed by ¹H NMR and HRMS. A549 and HCT116 cancer cell lines were selected for antiproliferative activity assays. Results All the compounds revealed antitumor activities and compound ZM528 showed the best antitumor activity against these two cell lines with IC₅₀ values of （5.1±4.8） μmol/L and （6.0±2.7） μmol/L, respectively. Conclusion The result indicated that bromoacetyl group of RRx-001 could be substituted with other covalent fragments.

OBJECTIVE To investigate the improvement effect and potential mechanism of “Layers adjusting external application” paste on synovial fibrosis （SF） in rats with knee osteoarthritis （KOA）. METHODS Male SD rats were randomly divided into sham operation group， KOA group and Layers adjusting external application group， with 8 rats in each group. KOA model was induced by the anterior cruciate ligament disruption method in KOA group and Layers adjusting external application group. Fourteen days after modeling， the Layers adjusting external application group was given “Layers adjusting external application” paste [Sanse powder （8 g for every 100 cm2）， Compound sanhuang ointment （5 g for every 100 cm2）] on the knee joint， 8 h every day， for 28 d in total. After the last administration， the degree of synovitis and fibrosis in rats was observed， and Krenn scoring was performed in each group. The expressions of collagen Ⅰ， high mobility group protein B1 （HMGB1） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65） were detected in the synovial membrane； the contents of interleukin-1β （IL- 1β）， IL-6 and tumor necrosis factor-α （TNF-α） in serum as well as the expressions of fibrosis-related and HMGB1/Toll-like receptor 4 （TLR4）/NF-κB signaling pathway-related proteins and mRNA were detected in synovial tissue. RESULTS Compared with the sham operation group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement， the inflammatory cell infiltration and collagen fiber deposition were obvious； the positive expressing cells of collagen Ⅰ， HMGB1 and p-NF-κB p65 were increased significantly； the contents of IL-1β， IL-6 and TNF-α in serum， the expressions of fibrosis-related protein （transforming growth factor-β， collagen Ⅰ， tissue inhibitor of metalloproteinase 1， α-smooth muscle actin） and their mRNA as well as theexpressions of HMGB1， TLR4 protein and their mRNA， the expressions of p-NF-κB p65 protein and NF-κB p65 mRNA were all increased significantly in synovial tissues of rats （P＜0.01）. Compared with the KOA group， the pathological changes in the synovial tissue of rats in Layers adjusting external application group were significantly improved， and the above quantitative indicators were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS “Layers adjusting external application” paste could significantly improve SF in KOA rats， the mechanism of which may be associated with the inhibition of the activation of HMGB1/ TLR4/NF-κB signaling pathway.

Objective:To analyze the relationship between aquaporin 1 (AQP1) level and vascular calcification in patients with diabetes nephropathy.Methods:A total of 125 diabetic nephropathy patients admitted to Suzhou Hospital of Nanjing Medical University from March 2020 to March 2023 were retrospectively selected as case group. The case group was divided into group A (diabetes nephropathy stage Ⅰ and Ⅱ) with 31 cases, group B (diabetes nephropathy stage Ⅲ) with 32 cases, group C (diabetes nephropathy stage Ⅳ) with 39 cases, and group D (diabetes nephropathy stage V) with 23 cases. In these patients, 51 cases had vascular calcification, taken as the calcification group, and 74 cases had no vascular calcification, taken as the non calcification group. Sixty volunteers who underwent health examinations in the same hospital were selected as the control group. Receiver operating characteristic curve was used to analyze the predictive value of AQP1 on vascular calcification in diabetes nephropathy patients and to explore the related factors of vascular calcification in diabetes nephropathy patients.Results:Compared with the control group, AQP1 level and calcification rate in groups A, B, C and D were higher: 6.41 ± 1.04, 7.93 ± 1.23, 9.50 ± 1.52 and 11.37 ± 2.01 vs. 3.83 ± 0.56 ng/L, 6.45% (2/31), 28.13% (9/32), 51.28% (20/29) and 86.96% (20/23) vs. 0 ( P<0.05). Compared with group A, the level of AQP1 and calcification rate in groups B, C and D were higher ( P<0.05); compared with group B, the AQP1 level and calcification rate in groups C and D were higher ( P<0.05); compared with group C, the level of AQP1 and calcification rate in group D were higher ( P<0.05). Compared to the non calcification group, the levels of uric acid, homocysteine and cystatin C in calcification group were higher: (313.82 ± 38.72) μmol/L vs. (253.42 ± 30.14) μmol/L, (20.03 ± 3.01) μmol/L vs. (15.01 ± 2.71) μmol/L, (1.73 ± 0.26) mg/L vs. (1.30 ± 0.17) mg/L ( P<0.05). AQP1 was positively correlated with uric acid, homocysteine, and cystatin C ( P<0.05). The area under the curve of AQP1, uric acid, homocysteine and cystatin C in predicting vascular calcification in patients with diabetes nephropathy were 0.892, 0.803, 0.738 and 0.763, respectively. Taking whether vascular calcification occurs in patients with diabetes nephropathy as the dependent variable (no = 0, yes = 1), the variables of P<0.05 in the single factor analysis were selected for multivariate Logistic regression analysis. The results showed that uric acid, homocysteine, cystatin C and AQP1 were the main factors affecting vascular calcification in patients with diabetes nephropathy ( P<0.05). Conclusions:Serum AQP1 has a high predictive value for vascular calcification in diabetes nephropathy patients, and is expected to be used as a biomarker for early diagnosis of vascular calcification in diabetes nephropathy patients.

Objective:To investigate the efficacy of fruquintinib in the treatment of advanced colorectal cancer, and to analyze the risk factors for all-cause death of fruquintinib.Methods:The clinical data of 82 patients with advanced colorectal cancer in the First Affiliated Hospital of Bengbu Medical College from December 2020 to April 2022 were retrospectively analyzed. The basic clinical data, efficacy and adverse reactions were recorded. The patients were followed up to October 2022, and all-cause death was recorded. Multivariate Logistic regression was used to analyze the risk factors of all-cause death in patients with advanced colorectal cancer treated with fruquintinib.Results:After treatment, partial remission was found in 9 cases, stable disease in 42 cases, disease progression in 31 cases. The objective remission rate was 10.98% (9/82), and the disease control rate was 62.20% (51/82). The incidence of adverse reactions was 75.61% (62/82), mainly hypertension and hand-foot syndrome. By the end of follow-up, 19 patients died and 63 survived. The incidences of body mass index (BMI)≥24 kg/m 2, lymph node metastasis, tumor located in the right colon and lactate dehydrogenase >200 U/L in all-cause death patients were significantly higher than those in survival patients: 36.51% (23/63) vs. 16/19, 39.68% (25/63) vs. 13/19, 44.44% (28/63) vs. 15/19 and 41.27% (26/63) vs. 14/19, and there were statistical differences ( P<0.01 or <0.05); there were no statistical differences in gender composition, age, smoking history, hypertension and postoperative complications between the two groups ( P>0.05). Multivariate Logistic regression analysis result showed that BMI≥24 kg/m 2, lymph node metastasis, tumor located in the right colon and lactate dehydrogenase >200 U/L were independent risk factors for all-cause death in patients with advanced colorectal cancer treated with fruquintinib ( OR = 9.275, 3.293, 4.687 and 3.985; 95% CI 2.440 to 35.265, 1.106 to 9.806, 1.398 to 15.715 and 1.277 to 12.430; P<0.01 or <0.05). Conclusions:Fruquintinib is effective in the treatment of advanced colorectal cancer. The BMI≥24 kg/m 2, lymph node metastasis, tumor located in the right colon and lactate dehydrogenase >200 U/L are independent risk factors for all-cause death in patients with advanced colorectal cancer treated with fruquintinib.

Objective:To explore the feasibility and therapeutic effect of Roux-en-Y anastomosis through a small incision in laparoscopic distal gastrectomy for gastric cancer.Methods:A retrospective analysis was conducted on the clinical data of 34 patients who underwent laparoscopic distal gastrectomy for gastric cancer through Roux-en-Y anastomosis through small incisions in the Gastrointestinal and Pancreatic Surgery Department of the Zhejiang Provincial People′s Hospital from August 2022 to May 2023.Results:Among the 34 patients, there were 27 males and 7 females, aged (63.6±14.6)years old. All cases underwent surgery successfully and there were no cases of conversion to open surgery. The reconstruction time of the digestive tract was (30.74±3.29)minutes, the intraoperative bleeding volume was (60.29±29.59)ml, the intraoperative lymph nodes were cleaned (32.00±11.00), the incision length of the specimen was (5.88±0.98)cm, the postoperative exhaust time was (1.88±0.73)days, and the postoperative hospitalization time was (11.94±3.87)days. There were no postoperative cases of anastomotic leakage, anastomotic stenosis, bleeding, or unplanned reoperation in patients. After a postoperative follow-up of 3-12 months, there were no recurrence or death cases, and no postoperative reflux cases during the follow-up period.Conclusions:Laparoscopic distal gastrectomy with Roux-en-Y anastomosis through a small incision can effectively reduce postoperative complications, especially the occurrence of postoperative reflux. In addition, this surgical procedure can simplify the surgical steps, shorten the surgical time, promote postoperative recovery, and improve postoperative quality of life.

Objective:To investigate the clinical effect of enteral nutrition support in the transformation therapy of advanced gastric cancer.Methods:Eighty-two patients with advanced gastric cancer treated by transformation in Zhejiang Provincial People′s Hospital from September 2019 to August 2021 were analyzed retrospectively. 41 patients in the observation group were treated with enteral nutrition support on the basis of routine transformation treatment; 41 patients in the control group received only routine transformation treatment. The nutritional related indexes such as prealbumin, total serum protein and albumin and immune related indexes such as CD4 + , CD8 + , CD4 + /CD8 + were detected before treatment and on the 7th day after the end of 3-cycle transformation treatment, and the above indexes and transformation success rate of the two groups were compared. Results:There was no significant difference in prealbumin, total serum protein, albumin, CD4 + , CD8 + , CD4 + /CD8 + between the two groups before treatment (all P>0.05). On the 7th day after three cycles of transformation treatment, the above indexes in the observation group were higher than those in the control group, with significant difference (all P<0.05). The success rate of transformation in the observation group was higher than that in the control group ( P<0.05). Conclusions:The rational use of enteral nutrition support in the transformation treatment of patients with advanced gastric cancer can significantly improve the nutritional status and immune function of patients, increase the tolerance to chemotherapy and improve the success rate of transformation.

Objective To search for novel potent 3-ester derivatives of arenobufagin and test their antitumor activities in vitro. Methods Target compounds were synthesized by esterification of arenobufagin with acids. CellTiter method was used to assay the in vitro antitumor activities. Results 3-Ester derivatives exhibited excellent antitumor activities against all the cancer cells. Conclusion Among the 3-ester derivatives, compound 2a had the best activities with the IC₅₀ of 4.0−91.7 nmol/L and appeared to be a valuable candidate for further study.

Objective:To observe the changes of neutrophil to lymphocyte ratio and lung function of patients defined by different TCM syndromes with acute exacerbation of chronic obstructive pulmonary disease.Methods:A total of 181 patients with acute exacerbation of chronic obstructive pulmonary disease in our hospital from January 2016 to Novenber 2018 were included and divided into 5 groups accoding to different TCM syndromes, which were wind-cold invading lung syndrome (26), external cold and internal fluid syndrome (40), phlegm-heat obstructing lung syndrome (48), phlegm-dampness blocked syndrome (48), an heart spirit confused by phlegm syndrome (19). Then tested the blood for each group, and calculated NLR; tested c-reactive protein, and lung function, and measured with COPD Assessment Test (CAT) and Modified British Medical Research Council (mMRC); conducted 6MWT, then the BODE index and Charlson Comorbidity Index (CCI) scores were calculated.Results:The NLR, CRP level in patients with external cold and internal fluid syndrome and an heart spirit confused by phlegm syndromeby phlegm were significantly higher than those of other syndrome ( P<0.05 or P<0.01), and FEV1% Pred was significantly lower than that of phlegm-dampness blocked syndrome ( P=0.024); the 6-minute walking distance of patients with external cold and internal fluid syndrome was significantly shorter than that of phlegm-heat obstructing lung syndrome and phlegm-dampness blocked syndrome ( P=0.006, P=0.024). The comparison of mMRC grades among the syndromes was statistically significant ( F=26.367, P=0.049). The BODE index of patients external cold and internal fluid syndrome was higher than that of patients phlegm-heat obstructing lung syndrome ( P=0.015), and the CCI score of patients an heart spirit confused by phlegm syndrome was higher than that of patients phlegm-dampness blocked syndrome ( P=0.012). The BODE index of patients with external cold internal fluid syndrome was significantly higher than that of phlegm-heat obstructing lung syndrome ( P=0.015). The CCI score of patients with mental disorder caused by phlegm was significantly higher than that of phlegm-dampness blocked lung syndrome ( P=0.012). Conclusions:There were significantly differences in neutrophil to lymphocyte ratio, CRP and 6-minute walking distance among different TCM syndromes in patients with acute exacerbation of chronic obstructive pulmonary disease. The inflammation in patients with external cold and internal fluid syndrome and mental disorder caused by phlegmare much severe, but there might be no difference in dyspnea and prognosis among TCM syndromes.

OBJECTIVETo compare the effect differences between row acupuncture at the gaps between phalanges and physical therapy for the dorsal stretch of fingers after cerebral infarction.

METHODSSeven-one cases were randomized into a row acupuncture at the gaps between phalanges group (group A, 37 cases) and a physical therapy group (group B, 34 cases). Body acupuncture was applied in the two groups. Row acupuncture at the 1st, 2nd, and 3rd gaps between phalanges was used in the group A, with continuous wave of electroacupuncture. The two electrodes of nerve injury therapeutic apparatus were put in the muscle belly center of extensor digitorum of forearm in the group B. All the treatments were given for 30 min in the two groups, once a day and 10 times as one course. Three courses were required with 3 d at the interval. The dorsal stretch of metacarpophalangeal joints and the muscle force of common extensor of fingers were compared between the two groups before and after treatment.

RESULTSCompared with those before treatment, the dorsal stretch of metacarpophalangeal joints and the muscle force of common extensor of fingers were improved after treatment in the two groups (all<0.05). There existed better effects in the group A on the dorsal stretch of the forefinger, middle finger and ring finger of metacarpophalangeal joints, as well as the muscle force of common extensor of fingers (all<0.05).

CONCLUSIONSRow acupuncture at the gaps between phalanges achieves better effect than physical therapy for the dorsal stretch of fingers after cerebral infarction, based on body acupuncture.