Objective To explore the biological mechanism of radiation resistance in esophageal squamous cell carcinoma(ESCC)and search for effective sensitization targets.Methods We retrieved 186 signaling pathways and related gene information from the MSigDB database.We also obtained RNA transcriptome data of ESCC patients using the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.We collected clinical pathological characteristics and tissue samples of 97 ESCC patients in our hospital from 2013 to 2020.Gene set variation analysis(GSVA)was made to calculate KEGG signaling pathway score,radiotherapy resistance related signaling pathways were screened through random forest algorithm,key genes in the pathway were screened using DESeq2,and a radiotherapy efficacy prediction model was constructed based on support vector machine-recursive feature elimination(SVM-RFE).The results were validated through experiments such as Western blotting and clonogenic assay.Results Based on the KEGG signaling pathway and GSVA enrichment score,random forest analysis showed that in the TCGA and GSE45670 cohorts,the contribution of tryptophan metabolism pathway enrichment values to radiation resistance in ESCC was significantly better than that of the other pathways.DESeq2 analysis revealed that key molecules in the tryptophan metabolism pathway,namely,IDO1,ALDH1B1,AOC1,INMT,AFMID and ALDH7A1,were significantly differentially expressed in the resistant and sensitive groups of ESCC.Based on the SVM-RFE algorithm,the AUC was 0.77,which could accurately predict the radiotherapy efficacy of ESCC.Western blotting experiments showed that IDO1 was highly expressed in ESCC cells,and IDO1 inhibitor treatment significantly inhibited the survival ability and radiosensitivity of KYSE-410 cells.In the enrolled patients of our hospital,immunohistochemical studies showed that IDO1 was highly expressed in the radiotherapy resistant group of ESCC and was associated with poor radiotherapy prognosis in ESCC patients.In addition,further testing showed that the expression of IDO1 in patient samples from our hospital was positively correlated with its PD-L1 expression,but negatively correlated with the infiltration ratio of CD3/CD8 immune cells.Conclusion Tryptophan catabolism is associated with radiation resistance in ESCC,and the key enzyme IDO1 in tryptophan metabolism can be used as a therapeutic target for radiosensitization in ESCC.

OBJECTIVE: To investigate the midterm clinical efficacy of medial patellofemoral complex (MPFC) reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia. METHODS: A retrospective analysis was carried out among adult patients who underwent arthroscopically assisted MPFC reconstruction between January 2014 and December 2020. Dejour classification was evaluated to grade trochlear dysplasia; tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati index were measured. Preoperative and postoperative patient-reported outcome measures (PROMs) were compared, including International Knee Documentation Committee (IKDC) score, Kujala score, Lysholm score and Tegner score. Information regarding returning-to-sport rate, re-instability events and complications was collected. Patellar tilt (PT), lateral patellar displacement (LPD) and bisect offset (BSO) ratio were measured based on axial computed tomography before and after surgery to assess the patellofemoral congruence. RESULTS: A total of 46 MPFC reconstructions in 43 patients were enrolled, including 16 male and 27 female. Mean age at surgery was (22.2±7.6) years (range: 14-44 years). Mean follow-up was (49.9±22.6) months (range: 18-102 months). The percentages of Dejour B, C and D dysplasia were 37.0% (17/46), 43.5% (20/46), and 19.6% (9/46), respectively. Mean Insall-Salvati index was 1.2±0.2 (range: 0.85-1.44), and mean TT-TG distance was (19.6±3.5) mm (range: 10.6-28.7 mm). At latest follow-up, there were significant improvements in all PROMs (P < 0.001): IKDC score, from 56.3±15.1 to 86.2±8.1; Kujala score, from 58.9±15.6 to 92.6±5.4; Lysholm score, from 63.7±15.0 to 94.0±5.7; Tegner score, from 3.1±1.4 to 4.7±1.4, and there were no significant differences in the improvements of the scores between the patients with Dejour B, C and D dysplasia. Overall, ninety percent of the patients returned to their preoperative sports level. One patient reported a postoperative subluxation, while no cases of infection, limited range of motion or patella fracture were observed. PT, LPD and BSO ratio were all significant altered (P < 0.001) after MPFC reconstruction. CONCLUSION Arthroscopically assisted MPFC reconstruction yielded satisfactory midterm clinical results for recurrent patellar dislocation with high-grade trochlear dysplasia. No significant differences of improvements in knee function were observed among the three types of high-grade trochlear dysplasia.
Humans ; Patellar Dislocation/surgery* ; Male ; Female ; Adult ; Arthroscopy/methods* ; Retrospective Studies ; Adolescent ; Young Adult ; Patellofemoral Joint/surgery* ; Recurrence ; Plastic Surgery Procedures/methods* ; Patella/surgery* ; Treatment Outcome

Objective To explore the biological mechanism of radiation resistance in esophageal squamous cell carcinoma(ESCC)and search for effective sensitization targets.Methods We retrieved 186 signaling pathways and related gene information from the MSigDB database.We also obtained RNA transcriptome data of ESCC patients using the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.We collected clinical pathological characteristics and tissue samples of 97 ESCC patients in our hospital from 2013 to 2020.Gene set variation analysis(GSVA)was made to calculate KEGG signaling pathway score,radiotherapy resistance related signaling pathways were screened through random forest algorithm,key genes in the pathway were screened using DESeq2,and a radiotherapy efficacy prediction model was constructed based on support vector machine-recursive feature elimination(SVM-RFE).The results were validated through experiments such as Western blotting and clonogenic assay.Results Based on the KEGG signaling pathway and GSVA enrichment score,random forest analysis showed that in the TCGA and GSE45670 cohorts,the contribution of tryptophan metabolism pathway enrichment values to radiation resistance in ESCC was significantly better than that of the other pathways.DESeq2 analysis revealed that key molecules in the tryptophan metabolism pathway,namely,IDO1,ALDH1B1,AOC1,INMT,AFMID and ALDH7A1,were significantly differentially expressed in the resistant and sensitive groups of ESCC.Based on the SVM-RFE algorithm,the AUC was 0.77,which could accurately predict the radiotherapy efficacy of ESCC.Western blotting experiments showed that IDO1 was highly expressed in ESCC cells,and IDO1 inhibitor treatment significantly inhibited the survival ability and radiosensitivity of KYSE-410 cells.In the enrolled patients of our hospital,immunohistochemical studies showed that IDO1 was highly expressed in the radiotherapy resistant group of ESCC and was associated with poor radiotherapy prognosis in ESCC patients.In addition,further testing showed that the expression of IDO1 in patient samples from our hospital was positively correlated with its PD-L1 expression,but negatively correlated with the infiltration ratio of CD3/CD8 immune cells.Conclusion Tryptophan catabolism is associated with radiation resistance in ESCC,and the key enzyme IDO1 in tryptophan metabolism can be used as a therapeutic target for radiosensitization in ESCC.

OBJECTIVE To study the antifungal activity of Huangqin decoction （HQD） against Trichophyton mentagrophytes and explore its mechanism. METHODS Minimal inhibitory concentration （MIC）， minimal fungicidal concentration （MFC）， mycelial length， spore germination rate， biomass and mycelium ultrastructure observation were performed to evaluate the antifungal activity of HQD against T. mentagrophytes. The effects of HQD on the cell wall of T. mentagrophytes were detected through sorbitol protection experiment. By measuring the content of ergosterol and the activities of squalene epoxide （SE） and lanosterol 14α-demethylase （CYP51）， the activity of HQD on the cell membrane of T. mentagrophytes was investigated. The effects of HQD on T. mentagrophytes mitochondria were investigated by determining the activities of malate dehydrogenase （MDH）， succinate dehydrogenase （SDH）， and ATPases （including sodium potassium ATPase， calcium magnesium ATPase， and total ATPase）. RESULTS HQD exhibited significant antifungal activity against T. mentagrophytes with MIC of 3.13 mg/mL and MFC of 25 mg/mL. After intervention with HQD， the mycelial length of T. mentagrophytes was significantly shortened （P＜0.05）； spore germination rate， biomass， the content of ergosterol in the cell membrane， the activities of SE and CYP51 in the cell membrane and MDH， SDH and ATPase in mitochondria were all decreased significantly （P＜0.05）； cell structure had been ；damaged to a certain extent， but the integrity of the cell wall had not been affected. CONCLUSIONS HQD shows significant antifungal activity against T. mentagrophytes， the mechanism of which may be associated with reducing the 0791- content of ergosterol in the cell membrane and the activities of SE， CYP51， and mitochondria-related enzymes.

OBJECTIVE To establish the fingerprint of Huangqin decoction （HQD）， to separate the phase states and screen the active phase states of antidermatophytic activity so as to study the spectrum-effect relationship. METHODS HPLC method was adopted using baicalin as reference， the fingerprints of 10 batches of HQD were drawn and the similarity evaluation was carried out using the Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition） to determine the common peak； the phase states of HQD were separated and characterized by high-speed centrifugation and membrane dialysis. The minimum inhibitory concentrations （MIC） of HQD and its different phase states against Trichophyton mentagrophytes were determined simultaneously. Using the peak area of 37 common peaks as independent variable， MIC as dependent variable， Pearson correlation analysis was performed by using SPSS 21.0 software. RESULTS A total of 37 common peaks were obtained in HPLC fingerprints of 10 batches of HQD， with the similarity higher than 0.99. Ten components were identified， such as albiflorin， paeoniflorin， liquiritin apioside， baicalin， melaleuca glycoside A， wogonoside， baicalein， glycyrrhizic acid， wogonin and oroxylin A. HQD was split into 3 phase states， such as precipitation phase （HQD-P）， solution phase （HQD-S） and nano phase （HQD-N）. The morphology of HQD-P was irregular granular， and the average particle size was 4.670-91.522 μm. The morphology of HQD-S was uniform flakes， and no particle size was detected. HQD-N was spherical in shape and the particle size was （129.0±12.9） nm. MIC values of each phase state of HQD against T. mentagrophytes in different phase states were HQD-N （4.64 mg/mL） ＜HQD （5.85 mg/mL） ＜HQD-P （7.37 mg/mL） ＜HQD-S （12.89 mg/mL） at the same dosage. Pearson correlation analysis showed that the peak area of 25 of the 37 common peaks （including identified components） was significantly negatively correlated with MIC （absolute values of correlation coefficient＞0.95 and P＜0.05）. CONCLUSIONS The chemical composition of 10 batches of HQD is consistent； HQD-N is the active phase state of HQD. Ten components such as paeoniflorin， liquiritin apioside and baicalin may be the main active components of HQD. The antidermatophytic effect of HQD is closely related to its component content and physical phase state.

Significantly increasing crop yield is a major and worldwide challenge for food supply and security. It is well-known that rice cultivated at Taoyuan in Yunnan of China can produce the highest yield worldwide. Yet, the gene regulatory mechanism underpinning this ultrahigh yield has been a mystery. Here, we systematically collected the transcriptome data for seven key tissues at different developmental stages using rice cultivated both at Taoyuan as the case group and at another regular rice planting place Jinghong as the control group. We identified the top 24 candi-date high-yield genes with their network modules from these well-designed datasets by developing a novel computational systems biology method, i.e., dynamic cross-tissue (DCT) network analysis. We used one of the candidate genes, OsSPL4, whose function was previously unknown, for gene editing experimental validation of the high yield, and confirmed that OsSPL4 significantly affects panicle branching and increases the rice yield. This study, which included extensive field phenotyping, cross-tissue systems biology analyses, and functional validation, uncovered the key genes and gene regulatory networks underpinning the ultrahigh yield of rice. The DCT method could be applied to other plant or animal systems if different phenotypes under various environments with the common genome sequences of the examined sample. DCT can be downloaded from https://github.com/zt-pub/DCT.

OBJECTIVETo investigate the relationship between serum/follicular fluid fetuin B levels and outcome offertilization (IVF).

METHODSInfertility women (28 with low fertilization rates, 44 with normal fertilization rates) receiving IVF in Women's Hospital of Zhejiang University School of Medicine during June and December 2016 were enrolled in the study. Serum/follicular fluid fetuin B levels were measured with ELISA method. Correlations of serum and follicular fetuin B level with fertilization outcome of IVF were analyzed with Pearson correlation coefficient and receiver operating characteristic (ROC) curve.

RESULTSA positive correlation between serum fetuin B and follicular fluid fetuin B levels was observed (=0.675,<0.01). Both serum and follicular fluid fetuin B levels in women with low fertilization rates of IVF were lower than those in women with normal fertilization rates[(6.09±1.31) μg/mL vs. (7.13±1.47) μg/mL,=3.050,<0.05; (5.13±0.96)μg/mL vs. (6.22±1.33) μg/mL,=3.755,<0.01]. ROC analysis showed that the area under curve (AUC) of serum fetuin B level in predicting fertilization rate was 0.832 (95%:0.729-0.934,<0.01), and 6.08 μg/mL could be used as cut-off value.

CONCLUSIONSSerum fetuin B level is correlated with follicular fluid fetuin B level, and it may be used for predicting the fertilization outcome of IVF.

Objective To observe the effect and safety of the endovascular hypothermia through hypothermic intravenous infusion device in the treatment of patients with severe craniocerebral injury compared with conventional surface cooling. Methods A total of 66 cases of patients with severe cranio-cerebral injury were randomly divided into the observation group and the control group with 33 cases in each group according to envelop randomization. The control group received surface cooling, and the observation group was given surface cooling plus endovascular hypothermia through hypothermic intravenous infusion device. The target temperature was 35 ℃maintained for 3-5 days, and natural rewarming was applied at the speed of 0.1-0.5℃/h to 36.0-37.3℃. The time to reach target temperature, the constant stability, the incidence rate and severity of complication such as shiver, arrhythmia, skin injury and agitation were recorded and compared between two groups, as well as the heart rate, breathing rate, pulse rate, blood pressure and Glasgow Coma Scale (GCS) scores after 72 h of treatment. Glasgow Outcome Scale scores 30 days after treatment and nursing workload were also calculated and compared. Results The cooling speed, time to reach target temperature and the ability to maintain at 35℃were (1.3±0.2)℃/h, (2.3±0.2) h and (6.5± 1.8)%in the observation group, respectively, compared with (0.5±0.1)℃/h, (3.6±0.6) h and (11.3±2.2)%in the control group, which had significant differences (t=1.862, 2.112, 2.408,P < 0.05). The occurrence rates of shiver, arrhythmia, skin damage and dysphoria and restlessness in the observation group were 33.33%(11/33), 9.09%(3/33), 6.06%(2/33) and 27.27%(9/33), respectively, which were much lower than those in the control group 84.85%(28/33), 15.15%(5/33), 33.33%(11/33), 54.55%(18/33),χ2=1.764-2.733,P<0.05. The heart rate, breathing rate, pulse rate, systolic blood pressure and GCS score after 72 h of treatment were(68.31 ± 3.73)times/min,(16.60 ± 1.52)times/min,(136.35 ± 3.71)mmHg(1 mmHg=0.133 kPa),(34.61 ± 1.05)℃, (9.91±4.05)points in the observation group, while(58.31±3.62)times/min,(19.81±1.83)times/min,(150.66± 2.70)mmHg,(35.65 ± 1.36)℃,(7.63 ± 3.17)points in the control group, and there were significant differences between two groups(t=2.275-3.035, P < 0.05).Besides, the ice-changing ice and turning-over time in the observation group were both remarkably reduced compared with control group, (14.03±3.11) min/h vs (38.12± 2.70) min/h (t=3.356, P<0.05) , (15.08±3.07) min/h vs (26.16±2.54) min/h ( t=3.021, P<0.05). Patients with good recovery, mild disability, severe disability, death in the observation group were 16, 13, 3 and 1 case, while 6, 11, 9, 7 cases in the control group (χ2=2.351,P < 0.05). Conclusions The endovascular hypothermia through hypothermic intravenous infusion device can rapidly reduce and effectively maintain target temperature, reduce the incidence rate of complication, improve the vital signs and decrease the nursing workload in order to improve neurological outcome in the treatment of patients with severe craniocerebral injury.

OBJECTIVE:To discuss the effects of Rujieping capsule on estrogen receptor(ER) and progesteron receptor(PR) of pathological tissues in rats with hyperplasia of mammary glands.METHODS:The rats were injected i.m with Estradiol benzoate injection for 25 days followed by the injection of Progesterone injection i.m for 5 days to establish the model of hyperplasia of mammary glands.Which were treated with high and low doses of Rujieping capsule respectively for 30 days with tamoxifen as positive control.RESULTS:Both tamoxifen and high and low doses of Rujieping capsules could lessen the symptoms of red swelling of nipples or hyperplasia of mammary glands,lower the levels of E2 and PRL,enhance the level of progestone,lower the index of uterus,markedly reduce the number of layers of the ductal epithelial cells,reduce the levels of ER and PR in mammary glands,and suppress mammoplasia.CONCLUSION:Rujieping capsules is effective in the treatment of hyperplasia of mammary glands in rats by regulating the level of estrogen and improve pathomorphologic change of hyperplastic mammary glands.

OBJECTIVE:To study the immunoregularoty effect of Lappaconitine in S180 tumor-bearing mice.METHODS: Each mouse was inoculated hypodermically with S180 tumor cells and normal sodium suspension,24 hours later,all the mice were injected i.m.with Lappaconitine q.d for 10 consecutive days.The immune function of the S180 tumor-bearing mice was detected.RESULTS: In Lappaconitine-treated mice,serum IgG level was heightened significantly;the 2,4-DNFB-induced delayed type hypersensitivity was enhanced;the induction of transformation of lymphocytes into lymphoblast was achieved;the phagocytic function of reticuloendothelial system was enhanced significantly,and the immune function of red cells was promoted.CONCLUSION: Lappaconitine could inhibit the growth of S180 tumor cells and significantly enhance the cellular immune function of S180 tumor-bearing mice.