Objective To provide a toxicological basis for HMS-01 in future clinical trials, through genotoxicity testing of safety evaluation. Methods The genotoxicity of HMS-01 was evaluated by Bacterial Reverse Mutation Assay （Ames test） with Salmonella typhimurium. Results HMS-01 was non-mutagenic against Salmonella typhimurium at six doses of 20.6, 61.7, 185.2, 555.6, 1666.7, and 5000 μg/dish with （or without） a metabolic activation system. Conclusion HMS-01 was not found to be mutagenic in the dose range of this experiment.

Objective This study aims to observe the clinical effect of bone plate reduction in combination with a re-sorbable plate on large mandibular cysts.Methods Between October 2017 and September 2022,patients with large mandibular cysts in the presence of labial and buccal cortical bone were involved in the study.Intraoral approach was performed for bone plate reduction.Cone beam computed tomography(CBCT)scan was reviewed at 3,6,and 9 months postoperatively to observe postoperative complications.Osteogenic results were assessed at these times to determine the clinical outcomes of this procedure.Results Eleven cases with large mandibular cysts in the presence of cortical bone were evaluated.The average thickness of the cortical bone on the labial and buccal sides was measured to be about(1.98±0.37)mm before surgery,with a mean value of(0.73±0.17)mm at the thinnest part of the plate and up to 0.51 mm at the thinnest part of the plate.The cystic cavities were well re-vealed during the surgeries,which were completed suc-cessfully.Postoperatively,the wounds healed in one stage without infection.The percentages of cyst shrinkage were 20.01%,41.76%,and 73.41%at 3,6,and 9 months after surgery,respectively.Quantitative measurement of bone mineral density in the jaws by CBCT with MIMICS software.The bone mineral densities of the adult bone were 313.78,555.85,and 657.45 HU at the 3,6,and 9 month time intervals,respectively.No significant change in the patient's maxillofacial appearance were observed from the preoperative period as assessed by the patient's and observer's visual analog scale.Conclusion Bone plate reduction is an effective treatment for large mandibular cysts of the oral and maxillofacial re-gion with the presence of cortical bone.

Objective To explore the CT and MRI characteristic manifestations of nodular fasciitis(NF).Methods A retrospec-tive analysis was conducted on the imaging data of 27 cases pathologically confirmed NF,and their special CT and MRI signs were analyzed.Among them,21 cases underwent MRI examination,14 cases underwent CT examination,and another 8 cases underwent both CT and MRI examinations.Results Among the 27 cases of NF,16 cases were subcutaneous type,4 cases were intramuscular type,and 7 cases were intermuscular(fascial)type.Eleven cases were located in the head and neck,8 cases in the trunk,6 cases in the upper limbs,and 2 cases in the lower limbs.Fourteen cases underwent CT plain scan,and all lesions showed slightly low density,while 1 case showed mild enhancement on CT enhanced scan.On T1 WI,19 cases showed iso-or slightly hypointense signals,and 2 cases showed slightly hyperintense signals.On T2WI,16 cases showed inhomogeneous hyperintense signals and 5 cases showed homoge-neous hyperintense signals.Fifteen cases showed mixed hyperintense signals on diffusion weighted imaging(DWI).Among the 7 cases with MRI enhancement,5 cases showed significant inhomogeneous enhancement,and 2 cases showed rim enhancement."Fascial tail sign"was observed in 25 cases of NF;"double low signal sign"was seen in 16 cases of NF;"reverse target sign"was observed in 6 cases of NF lesions;peritumoral edema was seen in 9 cases;and small cystic degeneration and necrotic foci were found in 3 cases.Conclusion The imaging manifestations of NF have certain characteristics.When the tumor course is short and the tumor size is small and manifesta-tions such as"fascial tail sign""double low signal sign"and"reverse target sign"are present,the possibility of NF should be considered.

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Objective:To explore the mechanism of peritoneal dialysis solution (PDS)-induced peritoneal microinflammation through activation of ceramide (CER) in peritoneal dialysis model mice.Methods:Thirty 5-week-old male C57BL/6 mice weighing about 22 g were used to set up peritoneal dialysis models, and then were randomly divided into 4 groups: sham operation group (1.5 ml sterilized water, n=7), high glucose-PDS group (1.5 ml 4.25% PDS, n=8), high glucose-PDS+ acid sphingomyelinase (ASMase) inhibitor desipramine (DES) group (1.5 ml sterilized water+10 mg/kg DES, n=8), high glucose-PDS+Src kinase inhibitor PP2 group (1.5 ml sterilized water +1 mg/kg PP2, n=7), with intraperitoneal injection once a day. After 28 days, the mice were sacrificed to retain peritoneal tissues. HE staining and Masson staining were used to observe the histological changes of peritoneum. Immunohistochemistry was used to detect the Toll-like receptor 4 (TLR4) and macrophages. High performance liquid chromatography, liquid chromatography/mass spectrometry and immunofluorescence were used to detect the expression of ASMase and CER. Real-time quantitative PCR was used to detect the mRNA levels of c-Src, p-Src, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Western blotting was used to detect the protein levels of c-Src, and p-Src. Enzyme-linked immunosorbent assay was used to detect the serum C reactive protein (CRP), IL-6 and TNF-α. Results:(1) High glucose-PDS led to peritoneal hyperplasia, collagen deposition and fibrosis in the peritoneal dialysis mice, indicating successful modeling. Compared with high glucose-PDS group, peritoneal hyperplasia, collagen deposition and fibrosis of mice treated with DES and PP2 were significantly improved (all P<0.05). (2) Compared with sham operation group, ASMase activation and CER level of peritoneal tissues were significantly higher in high glucose-PDS group, and DES could significantly inhibit activated ASMase and increased CER expression caused by high glucose-PDS (both P<0.05). PP2 had no significant effect on ASMase activation and CER level (both P>0.05). (3) Compared with sham operation group, there were more TLR4 and macrophage positive staining cells in peritoneal tissues in high glucose-PDS group, and the mRNA expression levels of IL-6 and TNF-α in peritoneal tissues and serum CRP, IL-6 and TNF-α were higher (all P<0.05). DES and PP2 could significantly inhibit the increased TLR4, macrophages and related inflammatory factors induced by high glucose-PDS (all P<0.05). (4) Compared with sham operation group, c-Src and p-Src mRNA and protein expression levels of peritoneal tissues in high glucose-PDS group were significantly higher (all P<0.05). PP2 significantly inhibited the increased p-Src mRNA and protein levels caused by high glucose-PDS (both P<0.05), but had no significant effect on the mRNA and protein expression levels of c-Src (both P>0.05). DES had no significant effect on the mRNA and protein expression levels of c-Src and p-Src (all P>0.05). Conclusions:High glucose-PDS may enhance the expression of CER through stimulating the activity of ASMase, phosphorylate Src, activate TLR4 and induce inflammatory damage of peritoneum in peritoneal dialysis model mice.

Objective:To explore the effect of perioperative nursing based on enhanced recovery after surgery (ERAS) in patients undergoing off-pump coronary artery bypass (OPCAB) .Methods:From January 2018 to February 2020, 200 OPCAB patients admitted to Affiliated Hospital of Jining Medical University were selected as research subjects using convenience sampling method. The 100 patients admitted from January 2018 to January 2019 served as the control group, while the 100 patients admitted from February 2019 to February 2020 served as the observation group. The control group received routine perioperative nursing, while the observation group received perioperative nursing based on the ERAS. The postoperative ventilator assistance time, Intensive Care Unit (ICU) stay time, anal exhaust time, off-bed time after surgery, and postoperative hospital stay time were compared.Results:The observation group had shorter postoperative ventilator assistance time, ICU stay time, anal exhaust time, off-bed time after surgery, and postoperative hospital stay time compared to the control group, with statistically significant differences ( P<0.05) . Conclusions:Perioperative nursing based on the ERAS can accelerate the postoperative recovery process of OPCAB patients, which is worthy of clinical promotion and practice.

Objective:To investigate the effects of early sleep deprivation(SD) on depressive-like behavior and hippocampus synaptic plasticity in adult mice with chronic unpredictable mild stress(CUMS) model.Methods:Thirty 2-week-old clean grade male mice were randomly divided into control group (CON group), CUMS group and SD + CUMS group according to the random number table, with 10 mice in each group. The mice in SD + CUMS group were subjected with sleep deprivation for 4 hours once a day during puberty (3 ~ 6 weeks old), and then were stimulated by CUMS after adulthood (9 weeks old). The mice in CUMS group were subjected with CUMS at the age of 9 weeks. And the mice in CON group were not given any intervention.The depressive-like behavior was evaluated by body weight, sugar water preference, tail suspension test and forced swimming test.The density of dendritic spines of basal and apical neurons in hippocampal CA1 was measured by Golgi staining, the frequency and amplitude of miniature excitatory postsynaptic current(mEPSC) of pyramidal neurons in the hippocampal CA1 region of mice were measured by electro-physiological patch clamp technique.Graphpad prism 7.0 software was used for statistical analysis and mapping. One-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparison.Results:(1) After stress modeling, there were significant differences in body weight, sugar water preference percentage, forced swimming immobility time and tail suspension time among the three groups ( F=71.63, 39.82, 44.13, 43.07, all P<0.01). Compared with CON group, the mice in CUMS group and SD+ CUMS group had lower body weight ((25.51±0.37) g, (22.92±0.31) g, (20.12±0.27) g, both P<0.01), lower sugar water percentage preference ((87.40±1.65) %, (63.42±3.33) %, (49.68±3.70)%, both P<0.01), longer immobile time of forced swimming ((34.30±5.32) s, (119.20±12.03) s, (153.80±9.17) s, both P<0.01) and longer immobile time of tail suspension test((115.20±8.19)s, (156.80±4.35) s, (192.00±4.12) s, both P<0.01). Compared with CUMS group, SD+ CUMS group had lower body weight ( P<0.01), lower sugar water preference percentage ( P<0.05), longer immobile time in forced swimming test( P<0.05) and longer immobile time in tail suspension test( P<0.01). (2) Golgi staining results showed that the densities of dendritic spines of apical neurons and basal neurons in hippocampal CA1 area of the three groups were significantly different ( F=38.41, 41.34, both P<0.01). The densities of dendritic spines of basal and apical hippocampal neurons in CUMS group and SD+ CUMS group were lower than those in CON group ((7.74±0.22)/10 μm, (6.58±0.27)/10 μm, (5.00±0.13)/10 μm, both P<0.01), ((8.90±0.23)/10 μm, (7.63±0.30)/10 μm, (6.01±0.14)/10 μm, both P<0.01). Compared with CUMS group, the mice in SD+ CUMS group had lower densities of dendritic spines of basal and apical hippocampal neurons(both P<0.01). (3) Electrophysiological results showed that there were significant differences in the frequency and amplitude of mEPSC in hippocampal pyramidal neurons of the three groups ( F=38.90, 63.37, both P<0.01). Compared with CON group, the frequency and amplitude of mEPSC in pyramidal neurons of CA1 in CUMS group and SD+ CUMS group were significantly lower ((0.39±0.03)Hz, (0.20±0.02)Hz, (0.07±0.02)Hz, both P<0.01; (9.98±0.31)pA, (7.74±0.21)pA, 6.36±0.13)pA, both P<0.01). Compared with CUMS group, the frequency and amplitude of mEPSC in SD+ CUMS group were lower (both P<0.01). Conclusion:Adolescent sleep deprivation aggravates depressive behavior and hippocampus synaptic plasticity impairment in adult CUMS model mice.

OBJECTIVE: To analyze the expression of microRNA-106a(miR-106a) in renal cell carcinoma (RCC) and its correlation with clinicopathological characteristics and prognosis of patients. METHODS: Serum samples of 64 patients with newly diagnosed RCC were collected as the study group, and serum samples of 40 healthy individuals were used as the control group. Real-time fluorescence quantitative PCR was used to determine the expression level of miR-106a in each group. The correlation between miR-106a expression and clinicopathological characteristics of the patients was studied with single factor analysis and multiple Logistic regression model. Kaplan-Meier survival curve was used to analyze its correlation with the prognosis of patients. RESULTS: Before surgery, compared with the control group (1.17± 0.58), RCC patients with high- (9.15± 0.96) and low-expression(3.45± 0.37) had increased expression of miR-106a. Postoperatively, the expression level of miR-106a in both groups of patients decreased to 1.53± 0.18 and 1.75± 0.21, respectively. The area under the curve (AUC) of the diagnostic value of serum miR-106a for RCC was 0.782 (95% CI: 0.661-0.902). With an optimal cutoff value of 0.531, the sensitivity was 78.10% and the specificity was 75.00%. Serum miR-106a level of RCC patients with TNM stage T3 or T4, clinical stage II or III, lymph node metastasis, and recurrence were significantly increased. The high expression of serum miR-106a in RCC patients has an independent relationship with the tumor TNM stage and lymph node metastasis. Of the 64 follow-up patients, 4 were lost and 30 had died. Among them, the median survival time of patients in the miR-106a high expression group was 30 months, which was significantly shorter than that of the low expression group (52 months). CONCLUSION The serum level of miR-106a is elevated in RCC patients, and may be used as a molecular marker for the diagnosis of RCC. High serum expression of miR-106a is an independent predictor for tumor TNM stage and lymph node metastasis, as well as an independent predictor for poor prognosis of RCC patients.
Biomarkers, Tumor/genetics* ; Carcinoma, Renal Cell/genetics* ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms/genetics* ; MicroRNAs/genetics* ; Neoplasm Recurrence, Local ; Prognosis

Objective:To assess the prognostic value of modified Charlson comorbidity index (mCCI) combined with serum albumin for long-term prognosis in peritoneal dialysis (PD) patients.Methods:From January 1, 2007 to June 30, 2015, patients who started PD in Nanjing Drum Tower Hospital were enrolled in this retrospective cohort study. Clinical data including gender, age, underlying diseases, laboratory examination and prognosis were collected. The mCCI at the beginning of PD was calculated. Whether the duration of PD exceeded 5 years was used as an indicator to evaluate the prognosis. The patients were divided into≥5 years group and<5 years group according to the duration of PD, and the data were compared between the two groups. Cox regression model was constructed to analyze the influencing factors of all-cause death in PD patients. Multivariate logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the predictive value of mCCI and serum albumin levels on whether patients could maintain long-term PD.Results:Of the 183 patients included [males 106(57.9%), females 77(42.1%); (53.35±16.50) years old; 162 cases (88.5%) with hypertension, 55 cases (30.1%) with diabetes], 97 cases had PD duration for ≥5 years and 86 cases less than 5 years. The overall 5-year technical survival rate was 65.1%. At the beginning of PD, compared with the dialysis age≥5 years group, the patients in the dialysis age less than 5 years group had older age, higher mCCI, lower serum albumin level, and higher C-reactive protein (CRP) level (all P<0.05), but there were no significant differences in gender, education level, electrolyte, mean arterial pressure, high densitv lipoprotein (HDL), low-density lipoprotein (LDL) and PD adequacy index between the two groups (all P>0.05). Multivariate logistic regression analysis showed that increased age ( OR=1.022, 95% CI 1.000-1.043, P=0.046), increased mCCI ( OR=1.620, 95% CI 1.300-2.018, P<0.001) and decreased serum albumin ( OR=0.807, 95% CI 0.730-0.893, P<0.001) were independent predictors for the duration of PD<5 years. ROC curve analysis showed that the area under ROC curves ( AUC) of mCCI, serum albumin level and combined prediction probability of the two for the duration of PD<5 years were 0.647(95% CI 0.568-0.727), 0.655(95% CI 0.577-0.734), and 0.767(95% CI 0.700-0.835), respectively, indicating that the accuracy of combined parameters to predict survival outcome was higher than that of any single parameter. Multivariate Cox analysis showed that increased age ( HR=1.073, 95% CI 1.046-1.100, P<0.001), increased mCCI ( HR=1.198, 95% CI 1.044-1.375, P=0.010) and decreased serum albumin ( HR=0.904, 95% CI 0.843-0.969, P=0.004) were independent influencing factors for all-cause death in PD patients. Conclusions:Old age, high mCCI and low serum albumin level are influencing factors for dialysis age<5 years and all-cause death in PD patients. mCCI combined with serum albumin level can improve the accuracy of predicting the long-term dialysis in PD patients.

Objective:To investigate the recovery of patients with acute thallium poisoning after 9 years.Methods:A group of 14 patients with familial thallium poisoning who were admitted to our hospital in 2010 were followed up for 9 years.Results:Among the 14 patients with acute thallium poisoning, one patient died on the 14th day after poisoning, and all the other survivors were followed up 9 years later. The general condition of all the patients was significantly better than that of poisoning 9 years ago. The alopecia of all cases disappeared, the newborn hair grew normally, without gastrointestinal symptoms, numbness, pain in the limbs and mental symptoms. All the patients returned to normal intelligence and physical strength and had a normal life. One patient (No. 5) gave birth to 2 children successively after discharge. The first child was 6 years old and the second child was 2 years old. Both growth and intelligence were not different from those of the same age. Currently, the third pregnancy was more than 7 months. No.6 and No.10 patients were poisoned in their teenage and were currently all studying in university. No.6 patient suffered from Hashimoto's thyroiditis 7 years after poisoning, and he has been taking thiamazole tablets for two years. Poisoned infants, No.7, 8 ,11 and 12, were school-age children with normal growth, mental development and excellent academic performance. Among the 13 surviving patients, blood and urine samples from No. 1, No. 3, and No. 4 patients were collected, and no thallium concentration was detected, and biochemical examina-tion and neurological examination were all normal.Conclusions:Patients with acute thallium poisoning have a favorable prognosis according to the follow-up after 9 years. All patients have no obvious sequelae and have normal labor ability. Young women have normal fertility, and children have normal growth and mental development.