ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

Ferroptosis， a new form of programmed cell death different from apoptosis， necrosis， and autophagy， is closely associated with a variety of physiological and pathological processes. Iron-mediated accumulation of reactive oxygen species is the main inducement of ferroptosis， the mechanism of which is related to intracellular lipid metabolism， iron metabolism， and antioxidant defense pathways. Multiple signaling axes and regulators jointly regulate the occurrence and disruption of ferroptosis. Studies have demonstrated that ferroptosis regulates the growth and proliferation of tumor cells. Inducing ferroptosis in tumor cells can control the growth， metastasis， and multi-drug resistance of tumors. Therefore， the effect and mechanism of ferroptosis on tumor cells have become a hot topic in anti-cancer research. As the research advances， a variety of ferroptosis inducers has been used in the clinical chemotherapy for cancers and demonstrate significant efficacy. Accordingly， the development of ferroptosis-inducing anticancer drugs has become a new research direction for tumor treatment. Some active ingredients such as lycorine， oleanolic acid， dihydroartemisinin， pseudolaric acid B， and ophiopogonin B of Chinese medicines can induce ferroptosis in tumor cells via lipid metabolism， iron metabolism， system X_c^-， and GPX4/GSH to regulate the development of tumors， demonstrating a promising prospect in clinical treatment. Based on the theory of the mechanism of ferroptosis， this paper reviews the research progress in ferroptosis induced by active ingredients of Chinese medicines in tumor cells and describes the metabolic regulatory network of ferroptosis from signaling pathways and regulatory factors， providing new strategies for applying active ingredients of Chinese medicines in the treatment of tumors.

OBJECTIVE: To investigate short-term effectiveness of arthroscopic repair via modified subacromial viewing portal (hereinafter referred to as modified viewing portal) in treatment of LafosseⅠsubscapularis tendon tears. METHODS: A clinical data of 52 patients with LafosseⅠsubscapularis tendon tears, who underwent the arthroscopic repair via modified viewing portal between October 2020 and November 2022 and met the selective criteria, was retrospectively analyzed. There were 15 males and 37 females with an average age of 63.4 years (range, 41-76 years). Twelve patients had trauma history and the other 40 patients had no obvious inducement. The main clinical symptom was shoulder pain and the hug resistance tests were positive in all patients. The interval between symptom onset and admission ranged from 3 to 26 months (mean, 7.2 months). The shoulder pain and function were evaluated by visual analogue scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, and University of California Los Angeles (UCLA) score before operation and at 12 months after operation. The shoulder range of motion (ROM) of forward flexion, abduction, and external rotation and the internal rotation strength were measured before operation and at 3 and 12 months after operation. MRI was performed at 3-6 months after operation to assess the tendon healing and the structural integrity and tension of reattached tendon. Patient's satisfactions were calculated at last follow-up. RESULTS: All incisions healed by first intention, no complication such as incision infection or nerve injury occurred. All patients were followed up 12-37 months (mean, 18.5 months). The VAS, UCLA, and ASES scores at 12 months after operation significantly improved when compared with those before operation ( P<0.05). The ROMs of abduction and forward flexion and the internal rotation strength at 3 and 12 months significantly improved when compared with those before operation ( P<0.05); and the ROMs at 12 months significantly improved compared to that at 3 months ( P<0.05). However, there was no significant difference ( P>0.05) in the ROM of external rotation at 3 months compared to that before operation; but the ROM at 12 months significantly improved compared to that before operation and at 3 months after operation ( P<0.05). Thirty-one patients underwent MRI at 3-6 months, of which 28 patients possessed intact structural integrity, good tendon tension and tendon healing; 3 patients underwent tendon re-tear. At last follow-up, 41 patients (78.8%) were very satisfied with the effectiveness, 7 were satisfied (13.5%), and 4 were dissatisfied (7.7%). CONCLUSION Arthroscopic repair via modified viewing portal for Lafosse Ⅰsubscapularis tendon tears, which can achieve the satisfactory visualization and working space, can obtain good short-term effectiveness with low overall re-tear risk.
Male ; Female ; Humans ; Middle Aged ; Rotator Cuff/surgery* ; Rotator Cuff Injuries/surgery* ; Shoulder Pain ; Retrospective Studies ; Treatment Outcome ; Arthroscopy ; Shoulder Joint/surgery* ; Tendons/surgery* ; Range of Motion, Articular

BACKGROUND:Olfactory dysfunction is an early biological marker of various diseases.However,the neuroimaging mechanism by which olfactory dysfunction occurs following cerebral small vessel disease is unclear. OBJECTIVE:To explore the different neuroimaging mechanisms of olfactory function regulation in patients with cerebral small vessel disease and Parkinson's disease,and explore the potential application value of olfactory function assessment in patients with cerebral small vessel disease. METHODS:Neuropsychological and olfactory tests,high-resolution structural magnetic resonance and resting-state functional magnetic resonance data were collected in 80 patients with cerebral small vessel disease,44 healthy controls and 29 patients with Parkinson's disease.DPABI,SPM12 and SPSS were used to analyze and compare the amplitude of low frequency fluctuation,regional homogeneity and functional connectivity values between the cerebral small vessel disease,control and Parkinson's disease groups.Correlations between the significantly altered resting-state functional magnetic resonance imaging measures and olfactory and cognitive scores were evaluated. RESULTS AND CONCLUSION:Compared with the control group,low-frequency fluctuation amplitude of the right dorsolateral superior frontal gyrus and the regional homogeneity of the left wedge leaf were significantly reduced in the cerebral small vessel disease and Parkinson's disease groups.The right dorsolateral superior frontal gyrus and the left cuneiform lobe are the seed points.Compared with the Parkinson's disease group,the functional connectivity values of the right anterior cunei,inferior temporal gyrus,anterior central gyrus and dorsolateral superior frontal gyrus,left posterior central gyrus and inferior temporal gyrus were significantly enhanced in the control and cerebral small vessel disease groups.The left cuneiform lobe was the seed point.Compared with the control group,the functional connectivity of the left lingual gyrus was significantly weakened in the cerebral small vessel disease and Parkinson's disease groups.The functional connectivity values of the left middle temporal gyrus and the right posterior central gyrus were enhanced in the control group compared with the cerebral small vessel disease and Parkinson's disease group,and that was enhanced in the cerebral small vessel disease group compared with the Parkinson's disease group.Correlation analysis showed that the olfactory score and cognitive score were positively correlated in the cerebral small vessel disease group,and the regional homogeneity of the left wedge lobe was negatively correlated with the Montreal Cognitive Assessment Scale score,while the functional connectivity of left wedge lobe-left middle temporal gyrus in the Parkinson's disease group was positively correlated with the olfactory recognition score,and the functional connectivity values of the left wedge lobe-left posterior central gyrus and left wedge lobe-left lingual gyrus were positively correlated with the olfactory identification score and the total olfactory score,respectively.The regulation of olfactory function in patients with cerebral small vessel disease has a different neuroimaging mechanism from that of olfactory dysfunction in patients with Parkinson's disease.The olfactory function of patients with cerebral small vessel disease is related to cognitive function.It is speculated that the olfactory function following cerebral small vessel disease is a secondary change of brain dysfunction,while olfactory dysfunction following Parkinson's disease is directly caused by abnormal function of olfactory-related brain areas.Olfactory function assessment in patients with cerebral small vessel disease has potential application in predicting cognitive function.

Objective To observe the value of multimodal models established combined 18F-FDG PET/CT radiomics with clinical data for evaluating response of locally advanced head and neck squamous cell carcinoma(LA-HNSCC)to neoadjuvant immuno-chemotherapy.Methods Totally 213 LA-HNSCC patients were retrospectively enrolled and randomized into training set(n=170)and test set(n=43)at the ratio of 8∶2.Radiomics features of tumors on 18F-FDG PET/CT were extracted and selected from training set,and the independent clinical predictors were screened with sequential univariate and multivariate logistic regressions.Radiomics models,clinical models and combined multimodal models were constructed using different algorithms,including adaptive boosting(AdaBoost),decision tree,naive Bayes,random forest(RF),support vector machine(SVM)and extreme gradient boosting(XGBoost),respectively.The receiver operating characteristic(ROC)curves were drawn,and the area under the curves(AUC)were calculated to assess the efficacy of each model for predicting the response of LA-HNSCC to neoadjuvant immuno-chemotherapy,and the decision curve analysis(DCA)was performed to explore the net benefit of each model.Results Totally 110 radiomics features were selected,and CD4/CD8 ratio was the independent clinical predictor of the response of LA-HNSCC to neoadjuvant immuno-chemotherapy.Models based on AdaBoost and XGBoost algorithms had high and stable efficacy for predicting tumor response to neoadjuvant immuno-chemotherapy,among which the multimodal models had better performance(AUC=0.943,0.930)than radiomics models(AUC=0.939,0.925)and clinical models(AUC=0.903,0.910)in test set(all P＜0.05).Conclusion Multimodal models established combined 18F-FDG PET/CT radiomics with CD4/CD8 ratio were more effective for predicting response of LA-HNSCC to neoadjuvant immuno-chemotherapy than any single model.

Objective:To investigate the dosimetric factors associated with acute nausea and vomiting (RINV) during intensity modulated radiotherapy for nasopharyngeal carcinoma.Methods:General clinical data and organs at risk (OAR) doses from 130 newly diagnosed early nasopharyngeal carcinoma patients who received radiation therapy alone in Henan Cancer Hospital from February 2018 to February 2023 were retrospectively analyzed. Dosimetric parameters were recorded, and the correlation between the parameters and the degree of nausea and vomiting was statistically analyzed using univariate and multivariate logistic regression models.Results:All 130 patients had symptoms of ≥ grade 1 nausea and vomiting. In the comparison of dosimetric parameters between patients with < grade 2 and ≥ grade 2 nausea, except the brainstem V 20 Gy, all parameters showed statistically significant differences (all P<0.05). The inner ear D max, and D max, D mean, V 10 Gy, V 20 Gy, V 30 Gy of the throat, oral cavity, pharyngeal constrictor, dorsal vagal complex (DVC) showed statistically significant differences between patients with grade 1 and grade 2 nausea (all P<0.05). The results of multivariate regression analysis showed that DVC V 30 Gy was a significant influencing factor in predicting the severity of nausea ( OR=73.95, 95% CI: 4.66-1172.60, P<0.001), and there was a significant correlation between oral V 30 Gy and the severity of vomiting ( OR=37.69, 95% CI: 1.26-1125.42, P=0.04). Conclusions:Even if OAR are exposed to lower doses of radiation, nausea or vomiting symptoms can still occur. The occurrence of RINV is significantly associated with DVC and oral radiation doses.

Objective To explore the safety and feasibility of a modified superior mesenteric artery(SMA)approach in totally laparoscopic complete mesocolic excision(CME)and D3 lymphadenectomy for right colon cancer.Methods A retrospective analysis was performed on clinical data of 77 cases of totally laparoscopic radical surgery for right colon cancer from April 2021 to April 2023.Before August 2022,42 cases underwent traditional SMA approach(control group,only marking with the ileocolic vascular pedicle as the tail of SMA),while after August 2022,35 cases underwent modified SMA approach(modified group,marking with the Treitz's ligament and ileocolic vascular pedicle as the head and tail of SMA,respectively).There was no statistically significant difference in general information between the two groups(P>0.05).The intraoperative conditions,postoperative recovery,and postoperative complications were compared between the two groups.Results Compared with the control group,the modified group had a shorter surgical time[(147.3±35.8)min vs.(173.4±29.9)min,t =-3.428,P =0.001].There were no statistically significant differences in the number of lymph node dissection,number of positive lymph nodes,drainage volume,exhaust time,postoperative hospital stay,and incidence of complications between the two groups(P>0.05).Conclusion The modified SMA approach for totally laparoscopic radical resection of right colon cancer shortens the surgical time,reduces the difficulty and risk of surgery,and has high safety and feasibility.

Objective:To investigate the criteria for two-way referral of diabetes in China through systematic review.Methods:According to inclusion and exclusion criteria, articles on two-way referral criteria for diabetes in China were retrieved from databases of PubMed, Embase, Cochrane Library, CNKI and Wanfang from inception to July 15, 2023. The data were extracted, by author′s name, publish year, criteria for rupwards and downwards referral, sample size, study region, study type and main conclusions.Results:A total of 702 relavent articles were retrieved, and 15 of which were included in the analysis. Blood glucose levels were the basic criteria for two-way referral, The criteria for upward referral included fasting blood glucose, 2-h postpradial blood glucose, glycosylated hemoglobin and random blood glucose, but there were variations in measuement values. The criteria for downward referral included fasting blood glucose, 2-h postpradial blood glucose, glycosylated hemoglobin, with the variation in fasting blood glucose. Lipids and blood pressure were also included in the referral criteria in later literature, with the variation of blood pressure values. There was consensus on the upward referral criteria for patients with special types of diabetes and with newly diagnosed diabetes. In contrast, the referral criteria for diabetic complications were relatively vague, especially with the lack of severity classification for chronic complications.Conclusion:The two-way referral criteria for diabetes mellitus have been constantly developing, while the criteria for downwards referral to the community need to be further improved.

As a rare Chinese medicinal material， Paridis Rhizoma is mainly distributed in Yunnan， Guangxi， and Guizhou in southwestern China， with the effect of clearing heat and detoxifying， alleviating edema and relieving pain， cooling liver and tranquilizing mind. It is particularly effective for injuries from falls， fractures， contusions and strains， snake bites， cold wind-induced convulsion， and other diseases， which has been used for more than 2 000 years. According to modern research， polyphyllin Ⅱ， one of the main active components of Paridis Rhizoma， belongs to diosgenin in structure. It has the anti-tumor， anti-inflammatory， antiviral， antibacterial， immune-regulating， antioxidant， and multidrug resistance-reversing activities， showing good application prospect. Especially， the anti-tumor effect of polyphyllin Ⅱ has attracted wide attention， and the mechanism is inhibiting proliferation， migration， and invasion of tumor cells， inducing cell cycle arrest， apoptosis， and autophagy， suppressing angiogenesis， and modulating tumor microenvironment. However， the pharmacokinetic results show that polyphyllin Ⅱ has low bioavailability in vivo due to the low solubility， poor absorption， unsatisfactory distribution， and slow metabolism， which limit the clinical application. In recent years， there has been an explosion of research on the adverse reactions of polyphyllin Ⅱ， such as the strong hemolytic activity and obvious cytotoxicity to liver， kidney， myocardium and cardiovascular cells. Thus， papers were retrieved from "CNKI"， "VIP"， "Wanfang Data"， "PubMed"， "Web of Science"， and "Elsevier SD" with "Paris saponin Ⅱ"， "Polyphyllin Ⅱ" as the main keywords， and the pharmacological activities and mechanisms， pharmacokinetics， and adverse reactions were summarized. The findings are expected to serve as a reference for the in-depth research， development， and utilization of polyphyllin Ⅱ.