ObjectiveIn kinesin-3, the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A. The function of this neck hinge for controlling processive movement, however, remains unclear. MethodsWe made a series of modifications to the neck hinges of KIF13B and KIF1A and tested their movement using a single-molecule motility assay. ResultsIn KIF13B, the insertion of flexible residues before or after the proline differentially impacts the processivity or velocity, while the removal of this proline increases the both. In KIF1A, the deletion of entire flexible neck hinge merely enhances the processivity. The engineering of these hinge-truncated necks of kinesin-3 into kinesin-1 similarly boosts the processive movement of kinesin-1. ConclusionThe neck hinge in kinesin-3 controls its processive movement and proper modifications tune the motor motility, which provides a novel strategy to reshape the processive movement of kinesin motors.

Objective To explore the predictive value of cardiopulmonary exercise test (CPET) combined with clinical indexes in the postoperative complications. Methods The clinical data and CPET data (including lung function) of patients undergoing radical esophagectomy in Xuzhou Central Hospital from January 2018 to March 2022 were collected. Univariate analysis and multivariate logistic regression analysis were used to analyze the meaningful evaluation index for the occurrence of postoperative complications. Results A total of 77 patients with esophageal cancer were included, including 59 (76.6%) males and 18 (23.4%) females aged 47-80 years. There were 42 (54.5%) patients in the non-complication group and 35 (45.5%) patients in the complication group. Univariate analysis results showed that the occurrence of postoperative complications was significantly correlated with age, body mass index (BMI), smoking index, tumor stage, the length of postoperative hospital stay, peak work rate (WRpeak), peak kilogram oxygen uptake (VO2peak/kg), the ventilatory equivalent for carbon dioxide slope (VE/VCO2 slope), forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) and maximum expiratory flow rate (MMEF) (P<0.05). The results of multivariate logistic regression analysis showed that BMI [OR=1.35, 95%CI (1.03, 1.77), P=0.031], peakVO2/kg [OR=0.64, 95%CI (0.45, 0.93), P=0.018], oxygen uptake-anaerobic threshold (ATVO2) [OR=0.66, 95%CI (0.44, 0.98), P=0.044] and VE/VCO2 slope [OR=1.49, 95%CI (1.10, 2.02), P=0.011] were the related indexes of complications after radical resection of esophageal cancer. The sensitivity of BMI, VO2peak/kg, ATVO2/kg and VE/VCO2 slope in predicting postoperative complications was 82.10%, and the specificity was 87.44%, 95%CI (0.744, 0.955). Conclusion BMI, VO2peak/kg, ATVO2/kg and VE/VCO2 slope can be used as predictors for postoperative complications of esophageal cancer.

ObjectiveUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze the differences in chemical components between raw products and wine-processed products of Polygonatum cyrtonema rhizome. MethodUPLC-Q-Exactive Orbitrap MS was used to analyze the chemical compositions of P. cyrtonema rhizome before and after processing， and the effective response ions were extracted after raw data processing， and the differential compounds before and after processing were screened combined with multivariate statistical analysis and according to the conditions of variable importance in the projection（VIP） value>1， P<0.05， fold change（FC）>2 or FC<0.5， based on the retention time， quasi-molecular ions， fragment ions and other information， the components were identified in combination with the control products and the literature， and the significant difference compounds were identified by clustering thermal analysis and relative quantitative analyzed， in order to clarify the change rule of the main components in P. cyrtonema rhizome before and after processing. ResultA total of 72 differential constituents between raw products and wine-processed products were identified， including 15 alkaloids， 12 organic acids， 12 amino acids， 6 flavonoids， 4 saccharides and 23 others. There were a total of 18 significantly different components， among which 13 compounds， including L-malic acid， lactic acid and 9，12，13-trihydroxy-10-octadecenoic acid， showed an increasing trend in content after wine processing， 5 compounds such as trans-3-indoleacrylic acid， L-arginine， D-tryptophan， showed a decreasing trend after processing. ConclusionThe chemical components of P. cyrtonema rhizome are significantly different before and after processing， mainly organic acids， saccharides， amino acids， flavonoids and alkaloids， which can lay the foundation for the in-depth study of the processing mechanism of Polygonati Rhizoma.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Objective To observe the clinical efficacy of FANG's scalp acupuncture combined with timing auricular point pressing therapy in the treatment of insomnia patients with maintenance hemodialysis(MHD).Methods A total of 70 patients with insomnia on MHD were randomly divided into observation group and control group,with 35 patients in each group.Both groups were given conventional treatment,the control group was given oral use of Estazolam Tablets on the basis of conventional treatment,and the observation group was given FANG's scalp acupuncture combined with timing auricular point pressing therapy.Both groups were treated for a total of 4 weeks of treatment.After 1 month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Pittsburgh Sleep Quality Index(PSQI)score and the Kidney Disease Quality of Life Short Form(KDQOL-SF)score,as well as the scores of the Hamilton Depression Scale(HAMD)and the Hamilton Anxiety Scale(HAMA),were observed in the patients of the two groups before and after treatment.The changes in hemoglobin(Hb),serum creatinine(Scr),and blood urea nitrogen(BUN)levels were compared before and after treatment between the two groups,and the safety of the two groups was evaluated.Results(1)After treatment,the PSQI and KDQOL-SF scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI and KDQOL-SF scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the HAMD and HAMA scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving HAMD and HAMA scores,and the differences were statistically significant(P＜0.05).(3)After treatment,the Hb,Scr,BUN levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving Hb,Scr,BUN levels,and the differences were all statistically significant(P＜0.05).(4)The total effective rate was 77.14%(27/35)in the observation group and 62.86%(22/35)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(5)Comparison of the incidence of adverse reactions in the two groups of patients,the difference was not statistically significant(P＞0.05).Conclusion FANG's scalp acupuncture combined with timing auricular point pressing therapy in the treatment of insomnia patients with MHD can effectively improve the sleep quality of patients and alleviate anxiety and depression,so as to improve the quality of life of patients,with remarkable efficacy.

Objective:To investigate the changes of thyroid hormones and the flow velocity of superior thyroid artery in patients with Graves' disease and Hashimoto's thyrotoxicosis before and after treatment with methimazole.Methods:A case-control study was conducted to select 45 cases of Graves' disease and 45 cases of Hashimoto's thyroiditis from October 2021 to December 2022 in the Department of Endocrinology, North China University of Science and Technology Affiliated Hospital. The changes of thyroid hormone and blood flow velocity of superior thyroid artery in patients with Graves' disease and Hashimoto's thyroiditis before and after treatment with methimazole were analyzed. Measurement data satisfying normal distribution were expressed by xˉ±s, and the mean between two groups was compared by t test. Measurement data not satisfying normal distribution were expressed by M( Q1, Q3), and the median between two groups was compared by Wilcoxon rank sum test. χ 2 test was used to compare the constituent ratio of enumeration data among groups. Results:There was no significant difference in thyroid stimulating hormone (TSH) between the two groups before treatment, and there was no significant difference in TSH between the two groups after 1 month and 3 months of treatment (all P>0.05). The levels of free triiodothyronine (FT3) were (24.09±9.29) pmol/L and (17.41±9.36) pmol/L in Graves' disease group and Hashimoto's thyroiditis group respectively before treatment. FT4 were (60.23±20.82) and (43.47±21.71) pmol/L, respectively, and the peak stolie vloiy (PSV) were (69.53±5.70) and (52.65±4.64) cm/s, respectively in Graves' disease group and Hashimoto's thyroiditis group respectively before treatment. There were significant differences between the two groups ( t values wrere 3.39 and 3.74, Z=13.83, all P<0.001). The difference of FT3 between one month after treatment and before treatment was (-6.36±5.32) and (-12.64±9.08) pmol/L ( t=4.02, P<0.001) and the difference in FT3 between 3 months of treatment and before treatment was (-10.14±9.50) and (-17.80±11.17) pmol/L, respectively ( t=3.51, P<0.001) between the Graves disease group and the Hashimoto's thyroiditis group. The difference in FT4 between the Graves disease group and the Hashimoto's thyroiditis group after 1 month of treatment and before treatment was (-28.47±10.09) and (-20.57±14.48) pmol/L ( t=7.01, P<0.001), and the difference of FT4 was (-47.06±20.57) and (-30.17±20.54) pmol/L ( t=3.91, P<0.001) between the Graves disease group and the Hashimoto toxin group. The difference between one month after treatment and before treatment was (-13.10(-34.10,-2.60)) and (-10.50(-27.5,-0.20)) cm/s ( Z=2.63, P=0.009), respectively. The difference between 3 months and before treatment was (-31.40(-53.20,-12.70)) and (-19.90(-46.00,-4.70)cm/s ( Z=4.40, P<0.001)) between the Graves disease group and the Hashimoto's thyroiditis group, and the difference was statistically significant. Conclusion:Thyroid hormone levels were decreased after treatment with methimazole in patients with diffuse toxic goiter and Hashimoto toxemia, but the difference was not statistically significant. The PSV level of superior thyroid artery in patients with diffuse toxic goiter was significantly lower than that in patients with Hashimoto's thyrotoxicosis.

The overall health condition of patients significantly affects the diagnosis,treatment,and prognosis of endodontic diseases.A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy,as well as selecting appropriate therapeutic approaches.This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures,improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Objective:Progressive bone resorption and destruction is one of the most critical clinical features of middle ear cholesteatoma,potentially leading to various intracranial and extracranial complications.However,the mechanisms underlying bone destruction in middle ear cholesteatoma remain unclear.This study aims to explore the role of parathyroid hormone-related protein(PTHrP)in bone destruction associated with middle ear cholesteatoma. Methods:A total of 25 cholesteatoma specimens and 13 normal external auditory canal skin specimens were collected from patients with acquired middle ear cholesteatoma.Immunohistochemical staining was used to detect the expressions of PTHrP,receptor activator for nuclear factor-kappa B ligand(RANKL),and osteoprotegerin(OPG)in cholesteatoma and normal tissues.Tartrate-resistant acid phosphatase(TRAP)staining was used to detect the presence of TRAP positive multi-nucleated macrophages in cholesteatoma and normal tissues.Mono-nuclear macrophage RAW264.7 cells were subjected to interventions,divided into a RANKL intervention group and a PTHrP+RANKL co-intervention group.TRAP staining was used to detect osteoclast formation in the 2 groups.The mRNA expression levels of osteoclast-related genes,including TRAP,cathepsin K(CTSK),and nuclear factor of activated T cell cytoplasmic 1(NFATc1),were measured using real-time polymerase chain reaction(real-time PCR)after the interventions.Bone resorption function of osteoclasts was assessed using a bone resorption pit analysis. Results:Immunohistochemical staining showed significantly increased expression of PTHrP and RANKL and decreased expression of OPG in cholesteatoma tissues(all P<0.05).PTHrP expression was significantly positively correlated with RANKL,the RANKL/OPG ratio,and negatively correlated with OPG expression(r=0.385,r=0.417,r=-0.316,all P<0.05).Additionally,the expression levels of PTHrP and RANKL were significantly positively correlated with the degree of bone destruction in cholesteatoma(r=0.413,r=0.505,both P<0.05).TRAP staining revealed a large number of TRAP-positive cells,including multi-nucleated osteoclasts with three or more nuclei,in the stroma surrounding the cholesteatoma epithelium.After 5 days of RANKL or PTHrP+RANKL co-intervention,the number of osteoclasts was significantly greater in the PTHrP+RANKL co-intervention group than that in the RANKL group(P<0.05),with increased mRNA expression levels of TRAP,CTSK,and NFATc1(all P<0.05).Scanning electron microscopy of bone resorption pits showed that the number(P<0.05)and size of bone resorption pits on bone slices were significantly greater in the PTHrP+RANKL co-intervention group compared with the RANKL group. Conclusion:PTHrP may promote the differentiation of macrophages in the surrounding stroma of cholesteatoma into osteoclasts through RANKL induction,contributing to bone destruction in middle ear cholesteatoma.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

Objective:To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China.Methods:A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results:A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality ( OR=1.04, 1.09, 0.67, 95% CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions:Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.