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.

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

Objective:To investigate the popularization of non-iodized salt among residents in water-borne high iodine areas and the iodine nutrition status of key populations in Shandong Province.Methods:In 2021, monitoring was conducted on a county-by-county basis in 47 counties (cities, districts, hereinafter referred to as counties) in 9 cities of Shandong Province, in accordance with the newly designated high iodine areas in the "Definition of Water Source High Iodine Areas and High Iodine Disease Areas" (GB/T 19380-2016) and historical high iodine areas. In each monitoring county, administrative villages with a median water iodine level greater than 100 μg/L were sorted by water iodine value, and a systematic sampling method was used to select 5 administrative villages as monitoring sites to investigate the water improvement situation and the iodine level of residents' drinking water. Totally 40 non boarding students aged 8 to 10 from one primary school and 20 pregnant women were selected in each village location to collect household edible salt samples and random urine samples for testing salt iodine and urine iodine levels, and the B-ultrasound method was used for thyroid examination in children.Results:A total of 364 high iodine administrative villages had been monitored, all of which had completed water improvement with a water improvement rate of 100.0%. The median iodine content in residential drinking water was 20.3 μg/L, ranging from 0.1 to 869.1 μg/L; and 11 464 edible salt samples were collected from residents' homes, with a non-iodized salt rate of 82.7% (9 481/11 464). A total of 9 197 urine samples from children and 2 335 urine samples from pregnant women were tested, with median urinary iodine levels of 219.0 and 139.0 μg/L, respectively. A total of 9 197 children were examined for thyroid, with 262 cases detected and a goiter rate of 2.8%.Conclusions:The rate of non-iodized salt in high iodine areas of Shandong Province still needs to be improved. Children's iodine nutrition is above the appropriate level, while pregnant women are at an iodine deficiency level.

Objective:To explore the radiological damage to cells induced by the delayed particles of 9C-ions for heavy ion therapy, as well as the microdosimetric distribution and biological effects of these particles on a single model of V79 Chinese hamster lung cells. Methods:The Monte Carlo program was employed to simulate the endonuclear absorbed doses of α particles with various energies (3-10 MeV) transported in cells (cell radius RC = 10 μm, nucleus radius RN = 5 μm). Then, the result were compared with the S values ( SN←N, SN←Cy, and SN←CS) derived using the medical internal radiation dose (MIRD) method to demonstrate the feasibility of Monte Carlo simulations. Finally, the energy deposition of the delayed particles of 9C-ions generated at three sites (i.e., on the surface and in the cytoplasm and nucleus of the V79 cell model) during their transport in targets was simulated, and the result ing cell surviving fraction was analyzed. Results:Monte Carlo and MIRD method yielded differences in S values of 1.91%-4.95% for SN←N (nucleus to nucleus), 1.48%-5.11% for SN←Cy (cytoplasm to nucleus), and -1.99% to 0.80% for SN←CS(surface to nucleus), indicating highly consistent S values derived using both method(differences < 6%). When a 9C-ion decayed on the surface of the V79 cell model and the produced secondary particles entered the cell, the average endonuclear absorbed dose was 10 -2 Gy orders of magnitude, with a cell surviving fraction of about 88%. In the case where decay occurred in the cytoplasm, the cell surviving fraction was about 80%. However, when the 9C ion decayed in the nucleus, α particles had short ranges and deposited most of their energy in the cell (mean endonuclear absorbed dose: 0.1 Gy). In this case, severe cell damage was induced, with the cell surviving fraction reducing to about 53%. Conclusions:9C-ions emit secondary charged particles due to decay, among which α particles cause great damage to cells when entering the nucleus and trigger evident biological effects.

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 investigate the efficacy of 3D-printed segmental tumor prosthesis for reconstruction of bone defects after resection of weight-bearing long bone tumors in the lower extremity.Methods:A total of 71 patients who received 3D-printed segmental metal tumor prosthesis for reconstruction of bone defects from August 2015 to August 2021 at the Musculoskeletal Tumor Center of Peking University People's Hospital were retrospectively analyzed. There were 40 males and 31 females, aged 23.08±18.52 years (range, 10-63 years). Tumor types: 49 cases of osteosarcoma, 9 cases of Ewing sarcoma, 3 cases of chondrosarcoma, 3 cases of synovial sarcoma, 2 cases of pleomorphic undifferentiated sarcoma, 2 cases of rhabdomyosarcoma, 2 cases of bone metastasis, and 1 case of low-grade malignant tumor of mesenchymal origin. Ennecking stage of bone tumor: 19 cases of stage III, 52 cases of stage IIb. Tumor location: femur 43 cases, tibia 28 cases. Operative time, intraoperative bleeding, patient survival and postoperative complications were recorded. Kaplan-Meier curves for prosthetic survival were plotted. The osseointegration at the prothesis-bone interface was determined by combination of clinical presentation and imaging. Limb function scores were evaluated using the Musculoskeletal Tumor Society (MSTS) 93 function score.Results:All 71 patients successfully completed the operation and were followed up for 24.4±13.2 months (range, 6.6-65.4 months). At the last follow-up, 50 patients survived without disease, 12 survived with the disease, and the remaining 9 cases died with disease. A total of 11 cases showed prosthesis failure, including 1 case of aseptic loosening, 3 cases of screw breakage or periprosthetic fracture, 1 case of periprosthetic infection, and 6 cases of tumor progression involving the prosthesis. The Kaplan-Meier curve showed that the 1-year, 3-year and 5-year survival rates of prosthesis were 94.2%±2.8%, 86.1%±4.7% and 79.5%±9.2%, respectively. 62 patients received functional follow-up, and the MSTS93 functional score at the last follow-up was 23.95±5.03 points (range, 10-30 points), with an excellent rate of 90% (56/62). The score of femoral prosthesis was 24.63±4.97 points (range, 13-30 points) and the score of tibial prosthesis was 23.29±5.09 points (range, 10-29).Conclusion:3D-printed segmental tumor prosthesis for reconstruction of bone defect after resection of weight-bearing long bone tumors in the lower extremity has a relative high survival rate, a low incidence of prosthetic complications, and a good recovery of function, and it can be used as an option for the postoperative reconstruction of bone tumors in weight-bearing bones of the lower extremity.

ObjectiveOptimize the latex perfusion technique and apply it to the construction of a murine craniofacial venous vascular model.Methods A total of nine 8-week-old male C57BL/6 mice weighing (25.0±1.3) g were randomly divided into three groups: 60% latex physiological saline group, 60% latex heparin group, and 30% latex heparin group. After completion of the perfusion, the specimens were immersed in 4 °C formalin fixative for 24 h, followed by dissection, observation, and measurement of the extracranial blood vessel diameters. Results After 200 μL latex perfusion solution was injected into the external jugular vein, the supraorbital vein, infraorbital vein, temporal vein, retrofacial vein, masseter vein and external jugular vein were perfused in each group.After comparing the perfusion degree of the distal branches of blood vessels, sublingual vein and tip venule, it was found that the 30% latex heparin group had the best perfusion effect, followed by the 60% latex heparin group, and the 60% latex saline group had the worst perfusion effect.ConclusionThe optimized latex perfusion technique can effectively infuse the veins in the head and face of mice, and this technique can provide a good reference for the study of the direction and morphology of facial veins in mice.