ObjectiveTo dynamically observe the clinical symptoms and pathological changes in a rat model of vinorelbine-induced phlebitis via injection into the dorsalis pedis vein. MethodsTwenty-eight 11-week-old male SPF-grade SD rats were randomly divided into a model group (n=20) and a control group (n=8). The model group received a single injection of 0.1 mL vinorelbine solution (4 mg/mL) via the right hind limb dorsalis pedis vein, while the control group received an equal volume of normal saline via the same method. The occurrence and grading of phlebitis in both groups were observed and recorded daily. The volume of the injured limb was measured by the drainage method to calculate the swelling rate. The weight-bearing ratio of the injured limb was assessed using a bipedal balance pain meter, and the skin temperature of the injured limb was measured by infrared thermal imaging. These measurements were conducted for 9 consecutive days. Starting from day 1, three rats from the model group were euthanized every other day. A 1-cm segment of the vein extending proximally from the injection site was collected. Pathological changes in the vein tissue were examined by hematoxylin-eosin staining, and ultrastructural changes of the vascular endothelium were observed using scanning electron microscopy. ResultsCompared to the control group, the injected hindlimb of model rats showed redness and swelling on day 1, with the swelling rate peaking at (81.89±15.75) % on day 3 (P<0.001), then gradually alleviating and decreasing to (15.41±0.33) % by day 9 (P<0.01). Pain was observed in the affected limbs of model rats on day 1 and worsened markedly on day 3, with the weight-bearing ratio decreasing to (36.35±4.91)% (P<0.001). Meanwhile, the skin temperature of the lesion site increased, reaching (36.36±0.40) ℃ on day 5 (P<0.001). Both pain and fever returned to near normal levels by day 9. Phlebitis grading in the model group showed that 75.0% of rats were grade Ⅱ on day 1; grade Ⅲ and Ⅳ each accounted for 37.5% on day 3; from days 5 to 9, most rats exhibited cord-like veins, predominantly grade III. Venous tissue showed peripheral edema and inflammatory cell infiltration on day 1, which gradually progressed to intimal rupture, vessel wall thickening, and even lumen narrowing from day 3 to 9. The venous intima exhibited destruction of tight junctions between endothelial cells and adhesion of blood cells, progressing to roughened, wrinkled, and protruding intimal surfaces. ConclusionThe vinorelbine-induced phlebitis of dorsal foot vein in rat model is characterized by local redness, swelling, warmth, and pain from days 3 to 5, which largely resolve by day 9, although cord-like veins can still be observed. With disease progression, venous tissue develops edema, vessel wall thickening, and lumen narrowing. The venous intima shows rupture, roughening, and in some cases, complete loss.

ObjectiveTo dynamically observe the clinical symptoms and pathological changes in a rat model of vinorelbine-induced phlebitis via injection into the dorsalis pedis vein. MethodsTwenty-eight 11-week-old male SPF-grade SD rats were randomly divided into a model group (n=20) and a control group (n=8). The model group received a single injection of 0.1 mL vinorelbine solution (4 mg/mL) via the right hind limb dorsalis pedis vein, while the control group received an equal volume of normal saline via the same method. The occurrence and grading of phlebitis in both groups were observed and recorded daily. The volume of the injured limb was measured by the drainage method to calculate the swelling rate. The weight-bearing ratio of the injured limb was assessed using a bipedal balance pain meter, and the skin temperature of the injured limb was measured by infrared thermal imaging. These measurements were conducted for 9 consecutive days. Starting from day 1, three rats from the model group were euthanized every other day. A 1-cm segment of the vein extending proximally from the injection site was collected. Pathological changes in the vein tissue were examined by hematoxylin-eosin staining, and ultrastructural changes of the vascular endothelium were observed using scanning electron microscopy. ResultsCompared to the control group, the injected hindlimb of model rats showed redness and swelling on day 1, with the swelling rate peaking at (81.89±15.75) % on day 3 (P<0.001), then gradually alleviating and decreasing to (15.41±0.33) % by day 9 (P<0.01). Pain was observed in the affected limbs of model rats on day 1 and worsened markedly on day 3, with the weight-bearing ratio decreasing to (36.35±4.91)% (P<0.001). Meanwhile, the skin temperature of the lesion site increased, reaching (36.36±0.40) ℃ on day 5 (P<0.001). Both pain and fever returned to near normal levels by day 9. Phlebitis grading in the model group showed that 75.0% of rats were grade Ⅱ on day 1; grade Ⅲ and Ⅳ each accounted for 37.5% on day 3; from days 5 to 9, most rats exhibited cord-like veins, predominantly grade III. Venous tissue showed peripheral edema and inflammatory cell infiltration on day 1, which gradually progressed to intimal rupture, vessel wall thickening, and even lumen narrowing from day 3 to 9. The venous intima exhibited destruction of tight junctions between endothelial cells and adhesion of blood cells, progressing to roughened, wrinkled, and protruding intimal surfaces. ConclusionThe vinorelbine-induced phlebitis of dorsal foot vein in rat model is characterized by local redness, swelling, warmth, and pain from days 3 to 5, which largely resolve by day 9, although cord-like veins can still be observed. With disease progression, venous tissue develops edema, vessel wall thickening, and lumen narrowing. The venous intima shows rupture, roughening, and in some cases, complete loss.

AIM:To explore the molecular mechanism of Tiaopi Chengqi decoction (TpCqD) improving hyperthermia and high-protein food-induced hyperphagia mice based on transcriptomics. METHODS:C57 mice were randomly divided into a control group, model group, low-dose TpCqD group, high-dose TpCqD group, and domperidone group. The general condition of the experimental mice was observed and the average food intake was counted, and the rate of gastric emptying and intestinal propulsion was determined for each group of mice. H&E staining was used to observe pathological changes in gastric tissue. PAS staining was used to observe glycogen changes in gastric tissue. Pepsin activity was determined by colorimetry. pH value of gastric contents was measured by acid-base titration. Transcriptome sequencing was used to analyze the differential genes in gastric tissue, a volcano map and a cluster heat map were made for the differential genes, and KEGG was used to analyze the signal pathway enrichment of the differential genes. RT-qPCR verified the differential genes obtained by screening. RESULTS:After treatment with TpCqD, the body weight and average food intake of mice with food accumulation increased (P<0.05), and the intestinal propulsion rate and gastric emptying speed of mice with food accumulation accelerated (P<0.05). TpCqD could protect gastric tissue structure and glycogen degradation, increase pepsin activity (P<0.05), and reduce gastric content pH (P<0.05). Transcriptome results showed that TpCqD could regulate the expression of Acox2 and cilp2, regulate fat digestion and absorption, protein digestion and absorption, and pancreatic secretion signals. RT-qPCR showed that compare with model group, TpCqD up-regulated Acox2 (P<0.05) and down-regulated the mRNA level of cilp2 (P<0.05). CONCLUSION:TpCqD ameliorated digestive dysfunction in mice with high-calorie and high-protein diets leading to food accumulation involving the regulation of the fat and sugar metabolism genes Acox2 and cilp2, and pancreatic secretory signaling.

This study was designed to investigate the potential protective effect of isopimpinelline against para-chlorophenylalanine(PCPA)-induced pineal gland damage in rats.Forty male Sprague-Dawley(SD)rats were divided into four groups(n=10 each):a normal group,a model group,a melatonin-treated group(10 mg/kg),and an isopimpinelline-treated group(1.5 mg/kg).All groups,except for the normal,received intraperitoneal injection of PCPA(450 mg/kg)to induce pineal gland damage.Subsequent treatments were administered orally for 7 days.Sleep latency and duration were evaluated on the sixth day using the pentobarbital sodium sleep synergy test.After the treatment period,serum melatonin levels and pineal gland inflammation markers were assessed alongside oxidative and antioxidative parameters.Histological examinations of the pineal gland were conducted,and the expression of proteins related to the Nrf2 and NF-κB signaling pathways were quantified.Data showed that isopimpinelline alleviates the structural damage in the pineal gland of model rats,significantly elevated serum melatonin levels,and markedly improved sleep latency and duration(P＜0.05).Isopimpinelline activated the Nrf2 signaling pathway by inhibiting Keap1 expression,which facilitated the nuclear translocation of Nrf2 and upregulated the antioxidant proteins NQO1 and HO-1,thereby mitigating oxidative stress in the pineal gland(P＜0.05).Furthermore,isopimpinelline significantly reduced the levels of pro-inflammatory cytokines IL-2,TNF-α and IL-6.Isopimpinelline also suppressed the NF-κB signaling pathway,reducing the expression of NF-κB p65,IKKβ,and p-IKKβ proteins,as well as the nuclear translocation of NF-κB p65(P＜0.05),thereby providing anti-inflammatory benefits.In conclusion,isopimpinelline could protect pineal gland from damage by activating the Nrf2 signaling pathway and inhibiting the NF-κB pathway.

Objective:To describe the design, manufacture and use of three-dimensional (3D)-printed endoprosthesis for reconstruction after metaphysis-involved intercalary tumor resection and to evaluate its outcome.Methods:Forty-three patients who received metaphysis-involved intercalary tumor resection followed by 3D-printed endoprosthetic reconstruction in Musculoskeletal Tumor Center, Peking University People's Hospital between January 2018 and December 2021 were retrospectively reviewed. There were 25 males and 18 males with an average age of 20.1±15.2 years (range, 4-58 years). The pathological diagnosis included 24 cases of osteosarcomas, 6 cases of Ewing sarcomas, 5 cases of chondrosarcomas, 2 cases of pleomorphic undifferentiated sarcomas, 3 cases of soft-tissue sarcomas (liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor for each) and 3 others (adamantinoma, recurrent aneurysmal bone cyst and recurrent osteofibrous dysplasia for each). The tumors located at femur in 25 patients (58%), including 14 lesions involving distal femoral metaphysis and 11 lesions involving both proximal and distal metaphysis; the tumors located at tibia in 11 patients (26%), including 4 lesions involving distal tibial metaphysis, 5 lesions involving proximal tibial metaphysis and 2 lesions involving both proximal and distal tibial metaphysis; the tumors located at humerus in 7 patients (16%), including 1 lesion involving distal humeral metaphysis, 3 lesions involving proximal humeral metaphysis and 3 lesions involving both proximal and distal humeral metaphysis. The endoprosthesis was designed in a semi-modular fashion and consisted of three parts: a diaphysis-fixing component, a semi-modular lap joint component, and a custom-made 3D-printed metaphysis-fixing component which was designed as two types with 3D-printed porous bone-contacting surfaces according to the osteotomy plane (Type I on meta-diaphyseal region, Type II on meta-epiphyseal region). The functional outcome was assessed using Musculoskeletal Tumor Society (MSTS) 93 system.Results:All surgeries were accomplished sucessfully. The median resection length and the distance from osteotomy plane to adjacent joint was 16.0 (13.0, 22.0) cm and 4.5 (3.5, 6.0) cm, respectively. 59 metaphysis-fixing components were installed in 43 patients. Type I components were used in single and dual ends of endoprosthesis in 12 and 6 cases respectively. Type II components were used in single and dual ends in 15 and 5 cases respectively. Hybrid endoprosthesis with Type I and II components were used in 5 cases. The mean follow-up time was 26.0 (17, 37) months (range, 12-54 months). The mean MSTS 93 score was 29.0 (28.0, 30.0) points (range, 21-30 points). Implant failures were found in 5 patients, including 2 cases of aseptic loosening (loosening was observed in the cementing diaphysis-fixing stems while no evidence of loosening in metaphysis-fixing components) and 3 cases of local tumor progression. The 2-year implant survival rate was 90.3% (95% CI: 0.81, 0.99). Conclusion:Using 3D-printed intercalary endoprosthesis for reconstruction after intercalary resection of metaphysis-involved bone tumor shows satisfactory functional outcome and implant survival. Moreover, by assembling endoprosthetic components according to the different osteotomy plane, the semi-modularized endoprosthesis also provids a comprehensive and individualized reconstruction for patients with metaphysis-involved intercalary tumor.

Objective To establish and evaluate chemotherapeutic phlebitis model rats induced by vinorelbine via the dorsalis pedis vein.Methods Rats were divided randomly into control and 4 different concentration of vinorelbine-induced model groups.Control rats were injected with 0.1 mL normal saline via the dorsalis pedis vein of the hind limb,while other rats were injected with different concentrations of vinorelbine(2,3,4,5 mg/mL),as above.General observations were performed and the hind limb volume was measured daily for 7 consecutive days to calculate the swelling rate.The rats were then killed and histological changes in the dorsalis pedis vein were observed by hematoxylin and eosin staining.Microstructural changes on the surface of the vascular endometrium were observed by scanning electron microscopy.Results Injection of 2,3,4,5 mg/mL vinorelbine via the dorsalis pedis vein significantly induced hind limb swelling in a concentration-dependent manner,peaking on day 3 in each group.The phlebitis rates on day 7 were 50%in the 2 mg/mL group and 83.3%in the 3 mg/mL group.Phlebitis was also induced in the 4 mg/mL and 5 mg/mL groups,including grade Ⅲ in 66.6%and grade Ⅳ in 83.3%.Histopathology showed inflammatory cell infiltration,wall thickening,lumen stenosis,and thrombosis in the tissues surrounding the veins.Scanning electron microscopy showed destruction of tight junctions of venous endothelial cells,and a rough surface of the vascular lining,resultsing in blood cell adhesion.Conclusions Injection of 0.1 mL of 3～5 mg/mL vinorelbine via the dorsalis pedis vein could induce red,swollen,and cord-like veins,as well as infiltration of inflammatory cells around the vein,thickened vein walls,lumen stenosis,and thrombosis.In addition,the surface of the venous intima was rough and adhered to numerous blood cells.All these features are consistent with those of clinical chemotherapeutic phlebitis in terms of the symptoms and pathological structure.

OBJECTIVE：To establish the method for content determination of 6 components in Fuzheng guben granules ，such as 2，3，5，4′-tetrahydroxystilbene glucoside ，baicalin，icariin，scutellarin，baicalein and wogonin. METHODS ：HPLC method was adopted. The determination was performed on Dikma Diamonsil C 18 column with mobile phase consisted of acetonitrile- 0.1％ phosphoric acid aqueous solution （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelengths were set at 275 nm （0-8 min），320 nm（8-9 min）and 275 nm（9-33 min）. The column temperature was set at 25 ℃，and sample size was 10 μL. With baicalin as reference material ，the relative corr ection factors （fk/s） of other five components were calculated by multi-point correction method and slope correction method ；the retention time difference method was used to locate the chromatographic peaks ； the calculation values obtained by above 2 QAMS were compared with measured values of external standard method. RESULTS ： The linear range of 2，3，5，4′-tetrahydroxystilbene glucoside ，baicalin，icariin，scutellarin，baicalein and wogonin were 0.053-2.12， 0.163-6.52，0.059-2.36，0.021 6-0.864，0.03-1.2，0.021-0.84 μg（r＞0.999），respectively. RSDs of precision ，stability（12 h）and reproducibility tests were all lower than 3％. Average recoveries were 98.72％-99.82％（RSDs were 0.89％-1.24％，n＝9）. Using baicalin as reference material ，fk/s of multi-point correction method for 2，3，5，4′-tetrahydroxystilbene glucoside ，icariin，scutellarin， baicalein and wogonin were 1.172，0.528，1.479，1.820 and 2.534，respectively；fk/s of slope correction method were 1.234， 0.550，1.559，1.939，2.664. RSDs of 6 components in 10 batches of Fuzheng guben granules by 3 methods were 0.29％-2.77％ （n＝10），respectively. Pearson correlation coefficient was not lower than 0.999 9（P＜0.001）in measured values between QAMS and external standard method. CONCLUSIONS ：QAMS method is established successfully for simultaneous determination of 6 components in Fuzheng guben granules.

Objective:We designed and applied a novel, bionic megaprosthesis for distal femur, which substituted the hinged articulation with an artificial ligament and a constrained tibial insert in order to maintain articular stability and reduce stress and the risks of wearing, loosening and breakage.Methods:We reviewed the cases of distal femoral osteosarcoma in children population who were initially treated in our center during 2019. Twelve cases of bionic distal femoral prosthesis (bionic group) and 21 cases of fixed-hinge distal femoral prosthesis (control group) were included. In the bionic group, there were six female and six male with the mean age as 8.8±2.6 y. One patient had pathological fracture. Staging according to Enneking system included 1 case of stage IIA, 10 cases of stage IIB and 1 case of stage III. In the control group, there were seven female and fourteen male with the mean age as 8.6±2.2 y. Pathological fracture was seen in three cases. Staging included 15 cases of stage IIB and 6 cases of stage III.We investigated the peri-operative safety, oncological outcome, complication profiles and post-operative functional status of the bionic prosthesis by comparing the baseline data, operative data, and oncological and prosthetic outcomes between the two groups.Results:The two groups were comparable in terms of baseline data including gender, age, height, weight and onset duration, and operative data including duration of operation (126.7±27.9 min vs 143.3±38.9 min, P=0.203), intra-operative hemorrhage (162.5±212.3 ml vs 247.6±175.6 ml, P=0.224) and duration of wound drainage (6.3±2.4 d vs 6.4±3.4 d, P=0.908). The mean follow-up duration of bionic group was 16.0±4.7 months, during which time three patients had systemic progression and one of them died of disease. Another patient had local recurrence and subluxation of the prosthesis that was treated by amputation. Subluxation might be related to the huge tumor mass and excessive resection of the quadriceps femoris. As for the control group, the mean follow-up duration was 12.7±4.5 months. Three patients had systemic progression and all patients were still alive by last follow-up. Local recurrence was seen in two patients and was treated by excision. No prosthetic complications were seen in the control group. The averaged range of motion (ROM) was greater in the bionic group than that in the control group (120.6°±13.6° vs 92.0°±7.7°, P<0.05), but the MSTS 93 scores were similar between groups (29.1±0.9 vs 29.5±0.6, P=0.337). Conclusion:Compared with the fixed-hinge distal femoral prosthesis, the bionic prosthesis had good peri-operative safety, did not increase the risks of prosthetic complications, and could achieve a better range of motion and a similar functional status based on the results of short-term follow-up.

Objective To investigate the proliferative inhibition effect and mechanism of total saponins from marsdenia tenacissima on human liver cancer HepG2 cells. Methods Human liver cancer HpeG2 cells cultured conventionally were divided into the marsdenia tenacissima saponins A control group, the experimental group and the blank control group. The experimental group was treated with different mass concentrations of total saponins from marsdenia tenacissima (0.14, 0.29, 0.58, 1.15, 2.13 mg/ml), while the marsdenia tenacissima saponins A control group was treated with marsdenia tenacissima saponins A (1.0 mg/ml), and the blank control group was established stimultaneously. The methyl thiazolyl tetrazolium (MTT) method was used to detect the effect of total saponins from marsdenia tenacissima on the activity of HepG2 cells, and the cell morphology was observed by using inverted microscopy. The cell apoptosis rate was detected by using flow cytometry from Annexin V-FITC/PI staining. The expressions of bcl-2, bax and p53 were analyzed by using Western blot after the drug effect. Results The results of cell activity test showed that total saponins from marsdenia tenacissima could inhibit the proliferation of HepG2 cells at the concentration of 0.29, 0.58, 1.15, 2.13 mg/ml, which was positively correlated with the concentration. The half maximal inhibitory concentration (IC 50) of cell growth inhibition of total saponins from marsdenia tenacissima on HepG2 cells was 0.75 mg/ml. Under inverted microscopy, the adherent cells were significantly reduced, the cells fell off into clusters and the debris was increased after the effect of total saponins from marsdenia tenacissima. Moreover, flow cytometry showed that total saponins from marsdenia tenacissima could increase the late apoptosis rate of HepG2 cells (P< 0.01). Western blot showed that the expression of bcl-2 was 0.62±0.16, 0.31±0.15, 0.84±0.09 and 1.00±0.11 respectively in the experimental group (total saponins from marsdenia tenacissima 0.58 mg/ml and 2.13 mg/ml), the marsdenia tenacissima saponins A control group and the blank control group;the expression of bax protein was 0.75±0.10, 0.83±0.12, 1.00±0.14 and 0.15±0.02, respectively in the above four groups; the expression of p53 protein was 0.63±0.08, 0.78±0.11, 1.00±0.13 and 0.18±0.02 respectively in the above four groups. The protein expression of bcl-2 was decreased and the protein expressions of bax and p53 were increased in the experiment group, and there was a statistical difference between the experiment group and the blank control group (P< 0.05). Conclusions Total saponins from marsdenia tenacissima can upregulate the expression of bax by upregulating the expression of p53 gene, and inhibit the expression of bcl-2, which would cause the cascade reaction to induce the apoptosis of HepG2 cells. Its inhibitory effect can be realized through mitochondrial pathmay to induce apoptosis.

Objective To evaluate the safety and efficacy of denosumab in treatment of patients with pelvic giant cell tumor of bone (GCTB) during perioperative period. Methods This is a retrospective observational study. Twenty-three patients diagnosed with pelvic GCTB undergoing perioperative denosumab treatment in Musculoskeletal Tumor Center of Peking University People's Hospital from January 2014 to December 2016 were reviewed. The subjective adverse reactions and mandibular X-ray films were used to assess the drug safety. As for efficacy, imaging findings (including X-ray, CT, magnetic resonance imaging) were reviewed. MSTS-93 scoring system was applied in the postoperative functional assessment. Histological response rate, objective response rate, clinical benefit rate and event-free survival rate were all used to deficit the efficacy of denosumab in the treatment of pelvic GCTB combined with surgery. All the results of postoperative were compared statistically with pelvic GCTB patients who underwent surgery in the same hospital from 1999 to 2009. Results All the patients were firstly diagnosed as classic GCTB except for one case which was malignant pelvic GCTB. All patients received denosumab preoperatively and/or postoperatively, and the average number of medications was 8.43. According to the surgical patterns, patients were divided into intralesional surgery group (13 cases) and wide resection group (10 cases). The follow-up was 5-47 months(mean:27.30 months),recurrence was observed in 2 cases in the intralesional surgery group, none in the wide resection group. After drug administration, 13 cases were partial response, 7 cases were stable disease, the objective response rate was 65.0 % (13/20), and the histologically clearance rate of giant cells was 85.0 % (17/20). No case of osteonecrosis of the jaw was observed in this study, and all laboratory indicators were normal. The average postoperative MSTS-93 score was 26.87. Compared with pelvic GCTB patients who underwent surgical treatment from 1999 to 2009, in the intralesional surgery group, there was no significant difference in the recurrence rate [15.4 % (2/13) vs. 30.8 % (4/13), P = 0.514], but the limb function was significantly increased (P= 0.002). Conclusions Denosumab combined with surgery plays an important role in the multidisciplinary treatment of pelvic GCTB. The neoadjuvant strategy can reduce patient's intraoperative blood loss by shrinking the tumor size which makes the intralesional curettage surgery possible, and also diminishing the recurrence rate. But more attention should be paid to secondary malignant GCTB during the use of denousmab.