Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective:To investigate clinical efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) .Methods:An ambispective study was conducted on 123 AD patients treated with dupilumab in Department of Dermatology, the Second Xiangya Hospital of Central South University from July 2020 to March 2022, clinical data were collected, and efficacy and safety of dupilumab were evaluated. Primary outcomes included scores of eczema area and severity index (EASI) , patient-oriented eczema measure (POEM) , peak pruritus numerical rating scale (NRS) and dermatology life quality index (DLQI) before and after 4-, 8-, 12- and 16-week treatment, and adverse reactions and events were recorded. Comparison of scores before and after treatment was performed using paired t test or repeated measures analysis of variance, Mann-Whitney U test was used for the comparison of efficacy among patients with different types of skin lesions or different IgE levels, and multiple regression model based on robust standard errors was used to analyze factors influencing the efficacy. Results:Among the 123 AD patients, 107 were enolled into the efficacy analysis, and 85 (79.44%) completed at least 4 weeks of treatment, including 6 (7.06%) achieving EASI75 and 23 (27.06%) achieving EASI50, and the EASI, NRS, POEM, DLQI scores (10.41 ± 6.72, 4.12 ± 1.74, 8.60 ± 4.29, 7.81 ± 4.38, respectively) significantly decreased compared with those before treatment (18.08 ± 10.69, 7.21 ± 2.01, 16.88 ± 5.74, 12.95 ± 5.95, respectively; all P < 0.001) in the 85 patients. Among the 107 patients, 47 (43.93%) completed at least 16 weeks of treatment. Among the 47 patients, 23 (82.14%) of 28 adults and 17 (89.47%) of 19 adolescents and children achieved 75% or greater improvement in EASI score; the EASI, NRS, POEM and DLQI scores before the treatment all significantly differred from those 4, 8, 12, 16 weeks after the treatment (all P < 0.001) , and all the scores were significantly lower at weeks 4, 8, 12 and 16 than at the previous adjacent time points (all P < 0.05) . At week 4 during the treatment, the EASI improvement rate was significantly lower in the AD patients with prurigo nodularis than in those without ( U = 151.00, P = 0.006) , while there was no significant difference in the EASI improvement rate between the AD patients with xeroderma and those without ( P > 0.05) ; at week 16 during the treatment, there was no significant difference in the EASI improvement rate between patients with prurigo nodularis or xeroderma and those without (both P > 0.05) . Multiple regression analysis based on robust standard errors at week 16 showed that the improvement degree in the EASI score was not correlated with the type of skin lesions ( β = 3.20, P = 0.075) , but correlated with age ( β = -0.22, P = 0.030) , whether patients were in adulthood ( β = 9.54, P = 0.049) , immediate family history ( β = 7.46, P = 0.017) ; the improvement degree in the NRS score was correlated with the type of skin lesions ( β = 0.55, P = 0.032) , age ( β = -0.04, P = 0.033) , weight ( β = -0.05, P = 0.020) , whether patients were in adulthood ( β = 2.06, P = 0.003) and whether patients received combined treatment with antihistamines ( β = -1.91, P = 0.001) . Adverse reactions: among the 123 patients, 6 (4.88%) developed conjunctivitis, and 2 (1.63%) developed facial erythema. Adverse events: vitiligo-like changes occurred on the right forehead of 1 patient, and 3 patients discontinued the treatment with dupilumab due to Henoch-Sch?nlein purpura, distal axonal damage in peripheral nerves in both upper limbs, and epilepsy, respectively. The causal relationship between these adverse events and dupilumab was unclear. Conclusion:Dupilumab is effective in the treatment of AD with high overall safety, and can serve as a new treatment option for AD patients with an unsatisfactory response to traditional treatment.

Acute abdomen in pregnancy can be divided into pregnancy-related and non-pregnancy-related type. This article reviewed the different types of acute abdomen caused by gynecological problems during pregnancy. Also, the progress of laparoscopic surgical technique and the perioperative management and the influence of the operation on pregnancy outcomes in patients who developed acute abdomen and underwent laparoscopic surgery in pregnancy were also analyzed, to provide information for the application of emergency laparoscopic surgery in pregnancy.

Objective To explore the association of fibroblast growth factor-23 (FGF23) with abdominal aortic calcification(AAC) and adverse outcomes in maintenance hemodialysis patients.Methods One hundred and fourteen cases of MHD patients were collected prospectively.Serum intact FGF23 was detected by ELISA.Abdomen lateral plain was used as a criteria to determine the abdominal aortic calcification and the abdominal aortic calcification score was counted.Logistic regression analysis was used to determine the risk factors of AAC.Kaplan-Meier analysis was applied to compare the survival rate among different groups and COX regression analysis was used to determine the association of FGF23 and mortality in MHD patients.Results Seventy-six patients present abdominal aortic calcification.The median of AACS was 4.0(0.0,11.0).The median level of FGF23 was 7277.4(2535.0,9990.8) pg/ml.The median follow-up duration was 72.0(67.8,72.8) months.During the follow-up,22 patients (19.3％) died of all-cause death and 17 cases (14.9％) died of cardiovascular diseases.Serum FGF23 level was positively correlated with AAC (r=0.285,P=0.002).Logistic regression analysis showed that longer age (OR=1.059,95％CI:1.020-1.100,P=0.003) and dialysis vintage (OR=I.009,95％CI 1.000-1.017,P=0.039),smoking history (OR=3.010,95％CI 1.177-7.696,P=0.021) and higher FGF23 level(OR=2.831,95％CI 1.010-7.937,P=0.048) were independent risk factors of moderate to severe AAC in MHD patients.Kaplan-Meier survival curves showed that the patients with AACS≥ 5 had significantly higher all-cause mortality(P=0.028) and CVD mortality (P=0.035) than those with AACS ＜ 5.However,the Kaplan-Meier analysis showed no significant difference regarding the level of serum FGF23 with the all-cause and CVD mortality.Cox regression demonstrated that FGF23 was not associated with increased mortality risk,neither in crude nor in multivariate adjusted models.Conclusions Abdominal aortic calcification had a high prevalence in MHD patients.The all-cause and CVD mortality was higher in patients with moderate to severe AAC.FGF23 was an independent risk factor of moderate to severe AAC,but it can't yet be a predictor for the allcause and CVD mortality of MHD patients.

Objective To determine the relationship between serum soluble Klotho (sKL) level and adverse outcome in maintenance hemodialysis (MHD) patients.Methods One hundred and twenty nine cases of MHD patients were collected prospectively.Serum sKL was detected by ELISA.Abdomen lateral plain was used as a criterion to determine the abdominal aortic calcification.The abdominal aortic calcification score (AAC) was calculated.Cox regression analysis was used to determine the risk factor of cardiovascular death (CVD) in MHD patients.Kaplan-Meier showed the relationship between sKL and CVD in MHD patients.Results There were 27 cases (20.9％) of allcause death and 19 cases (14.7％) of cardiovascular death.The median sKL was 612.6(379.2-816.6) nig/L,and log[iPTH] was an independent factor of sKL concentration.Low sKL had high AAC and CVD death rate.Kaplan-Meier method showed that the all-cause death rate was similar between two groups,and CVD death rate increased significantly in low sKL patients (P=0.036).Cox regression indicated that lower sKL level was associated with high CVD death rate [OR=0.352,95％CI(0.127-0.977),P=0.045].After adjustment for the general condition,biochemical indicators,the relationship still existed [OR=0.331,95％ CI (0.117-0.933),P=0.037].In no or mild vascular calcification patients (AAC ≤4),compared with high sKL patients,low sKL patients had no significant difference rate in all-cause mortality.The CVD mortality was significantly higher in high sKL (P=0.035) compared with low sKL.In severe calcification group (AAC ＞ 4),all-cause death and CVD death rates were similar between different sKL groups (P=0.991 and 0.522,respectively).Conclusions Lower sKL has the high CVD death rate and sKL level decreasing is an independent risk factor for CVD death in MHD patients.The lower sKL concentration in MHD patients with no or mild calcification may predict CVD mortality.This study suggests that sKL levels may be helpful in predicting the outcome of patients with MHD.

Objective To investigate the relationship between the variation of endothelial progenitor cells (EPC) number and cardiovascular diseases (CVD) in maintenance hemodialysis (MHD) patients ,and discuss the function of EPC in the progression of CVD in MHD. Methods One hundred and fifteen MHD patients over 18 years whose dialysis vintage was over six months from Department of Nephrology, Renji Hospital, Shanghai Jiao Tong University School of Medicine were enrolled. They were divided into CVD group and non ? CVD group by medical history, electrokardiographie (EKG), cardiac ultrasound, peripheral vascular imaging and cardiovascular imaging. Peripheral blood (5 ml) was collected for detecting EPC number by flow cytometry as CD34/CD133/vascular endothelial growth factor receptor 2 (VEGFR2) cells. The EPC number between CVD group and non?CVD group was compared. The relationship between the decrease of EPC number and CVD risks in MHD patients was analyzed by logistic regression analysis. In a three?year follow?up, the death and new CVD events of the two groups were compared in order to discuss the relationship between EPC number and adverse events. Results Among 115 MHD patients, the average age was 61.57 ± 12.76, male/female was 71/44, the average dialysis vintage was (86.24 ± 56.31) months, the average Kt/V was 1.69 ± 0.29 and average ultrafiltration volume was (2.48 ± 0.90) L. Forty?four patients in 115 (38.3%) were with concurrent CVD. The EPC number in CVD group was significantly lower than that in non CVD group (P=0.015). The CVD group had higher serum phosphate (P=0.013), higher glycosylated hemoglobin (P<0.001), but serum calcium, intact parathyroid hormone (iPTH) and other indicators had no significant difference between two groups. Multiple Logistic regression analysis showed that older age (OR=1.061), history of diabetes (OR=9.796), dialysis vintage (OR=1.015), serum phosphate (OR=3.766), decrease of EPC number (OR=0.909) were the independent impact factors of CVD events in MHD patients. There were 22 patients of the 115 MHD patients had encountered a new CVD event in a three?year follow?up between December 2012 and December 2015, 9 patients from the CVD group and 13 patients from the Non?CVD group, and there was no significant difference between two groups (P=0.776). Nine patients from the CVD group and 7 patients from the Non?CVD group died in the follow?up, and there was no significant difference (P=0.111). Seventy?one MHD patients from the non?CVD group were divided into two groups by the median of EPC number. There were 3 patients in the higher EPC number group encountered CVD events and 10 patients in the lower EPC number group encountered CVD events, which had significant difference (P=0.024). Conclusion The decrease of circulating EPC number may be related with CVD events in MHD patients. Even adjusted by age, sex, diabetes, dialysis vintage and serum phosphate, decreased EPC number is still the independent risk factor of CVD events in MHD patients. The decrease of EPC number in MHD patients may be used to predict the occurrence of cardiovascular events.

Objective To establish the quality standard of Radix Toddaliae Asiaticae. Methods Thin layer chromatography ( TLC) and high performance liquid chromatography ( HPLC) were used to identify and determine chloride nitidine and toddalolactone in Radix Toddaliae Asiaticae. The moisture and total ash contents were detected according to the methods recorded in appendix of Chinese Pharmacopeia (2010 edition) . Results Toddalolactone and chloride nitidine were detectable by TLC, the spots were clear and the dissociation was good. The established HPLC method was simple and accurate. The linear ranges of toddalolactone and chloride nitidine in Radix Toddaliae Asiaticae were 2.84~42.6 μg/mL and 25.6~385 μg/mL, and their recovery rates were 99.2 % ( RSD=1.12%) and 100 % ( RSD=0.71%) , respectively. The content of moisture was in the range of 75.8~98.9 mg/g and that of total ash was in the range of 12.4~33.6 mg/g. Conclusion The developed method is specific and accurate, and can provide useful reference for establishing quality standard of Radix Toddaliae Asiaticae.

Objective To analyze the relevant factors of cerebral stroke recurrence in order to provide reference for clinical prevention. Methods A total of 300 patients with cerebral stroke treated in our hospital from April 2012 to April 2015 were selected and divided into the primary onset group (206 cases) and the recurrence group (94 cases). The age, blood pressure, blood sugar, blood lipids, smoking, drinking, carotid atherosclerosis, type of stroke, family history of stroke and emotions of the two groups were compared. Univariate and multivariate analysis was conducted. Results The differences of patients' age, blood pressure, blood sugar, blood lipids, smoking, carotid atherosclerosis, family history of stroke, the respect such as emotional between two groups were statistically significant (P<0.05), the differences of drinking and stroke type had no statistical significance (P>0.05), and old age, hypertension, hyperglycemi a, hyperlipi-demia, smoking, carotid atherosclerosis, family history of stroke, emotional behavior disorder were independent risk fac-tors for recurrence of stroke(P<0.05). Conclusion For the patients with primary onset cerebral stroke and potential risk of cerebral stroke, their medical history and family history should be learned in detail, monitoring of their blood pres-sure, blood glucose and blood lipids should be enhanced, and meanwhile good life habits should be developed under guidance and positive and optimistic mentality should be cultured.

OBJECTIVETo investigate the molecular etiology of three patients with sporadic cleidocranial dysplasia (CCD) and to provide genetic counseling and prenatal diagnosis for the family members based on the identified mutations.

METHODSGenomic DNA was extracted from peripheral blood samples using a standard method. All 7 coding exons of the RUNX2 gene and their flanking intronic sequences were amplified by PCR and sequenced directly. The PCR products of the exons with mutations from the three patients were cloned into a T-vector. Positive clones were sequenced.

RESULTSThe three patients who have the typical CCD phenotypes involving clavicles, calvarium, stature, and teeth have carried various frameshift mutations in the RUNX2 gene. Patient 1 has a gross deletion of 80 nucleotides in exon 1 (c.227_306del), which caused a frameshift beginning at the Q/A repeat of the polypeptide and a premature termination (p.Ala76GlyfsX58). Patient 2 has a 2-bp duplication in exon 2 (c.471_472dupGG), which also caused a frameshift and a premature termination (p.Ala158GlyfsX19). Patient 3 has a T duplication in exon 7 (c.1321dupT), which caused a frameshift and a premature termination (p.Ser370PhefsX13) as well.

CONCLUSIONThe three novel mutations in RUNX2 are the underlying molecular mechanism for the CCD phenotypes of three sporadic Chinese patients, respectively. These have broadened the mutation spectrum of RUNX2 gene and provided a molecular basis for the genetic counseling and prenatal diagnosis for the affected families.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Cleidocranial Dysplasia ; genetics ; Core Binding Factor Alpha 1 Subunit ; genetics ; Exons ; Female ; Frameshift Mutation ; Humans ; Introns ; Male ; Molecular Sequence Data

Objective To explore the correlation between the syndromes of patients with gastric carcinoma and level of serum sE-cad. Methods Totally 190 cases of different syndromes of patients with gastric carcinoma were collected, and serum level of sE-cad was measured by ELISA. The correlation between the syndromes of gastric cancer and level of serum sE-cad was analyzed by SPSS16.0 software. Results The level of serum sE-cad of interior retention of blood stasis syndrome was significant different with that of deficiency syndrome of spleen and stomach, yin impairment syndrome due to stomach heat, deficiency syndrome of both qi and yin (P<0.05). Besides, this result was the same as the results of gender stratification analysis in men. The difference in serum level of sE-cad in the type of deficiency syndrome of spleen and stomach was significant different with that of deficiency syndrome of both qi and yin in women (P<0.05). Conclusion Level of serum sE-cad was correlated with syndrome type of patients with gastric carcinoma.