Objectives:To investigate the mutation of PIK3CA in colorectal cancer and to analyze their clinicopathological features, and evaluate their role in clinical treatment and prognostication.Methods:A total of 128 paraffin-embbeded tissue samples of colorectal cancer from Shanxi Cancer Hospital from 2018 to 2021 were collected. DNA was extracted from the samples, and next-generation sequencing (NGS) was used to detect PIK3CA mutation. The relationship between PIK3CA mutation, their clinicopathological features, and prognosis were analyzed.Results:Among the 128 colorectal cancer samples, there were 75 males and 53 females; with aged range 32-86 years, median 61.5 years, 27 (21.09%) had PIK3CA mutations. Colorectal cancer with PIK3CA mutation was more likely to occur in male patients ( P=0.007), which was related to tumor site ( P=0.032), tumor size ( P=0.029) and TP53 wild-type ( P=0.001). The common site mutations of PIK3CA mostly occurred in tumors with tumor mutation burden≥10 Muts/Mb ( P=0.031).PIK3CA mutation had no significant effect on the survival prognosis of patients, but the efficacy of anti-angiogenic therapy was poor in these patients. Conclusions:PIK3CA mutation is a common mutation in colorectal cancer and plays an important role in the occurrence and development of colorectal cancer. PIK3CA mutation may lead to resistance to anti-angiogenic drugs in colorectal cancer, but its impact on survival and prognosis to patients needs further study.

Objective To provide some evidence for early empirical treatment of infections caused by Pseudanonas aeruginosa(PA)and establish a certain foundation for further studies on its resistance mechanisms.Analyzed the resistance rate of PA and the phenotype characteristics for seven years at this hospital.Methods Using Whonet 5.6 software,the drug sensitivity data of PA isolated and reported from clinical specimens at Kunming First People's Hospital from 2016 to 2022 were analyzed annually.Imipenem,meropenem,ceftazidime,and cefepime were the main observation objects,statisticaly analyze the resistance of other antibiotics under different drug resistance combinations of the above-mentioned drugs Results A total of 1 920 strains of PA were detected in 7 years,with polymyxins exhibiting the lowest resistance rate at 1%.The average resistance rates for Amikacin,Gentamicin and Tobramycin were 6.4%,8.6%and 5.1%,respectively.The resistance rates of Quinolones,Piperacillin/Tazobactam,Ceftazidime,and Cefepime were similar,ranging from 10%～20%.Imipenem and Meropenem did not show better sensitivity,with resistance rates of 21.3%and 18.4%,respectively.The resistance rates of major antibiotics have fluctuated over the past 7 years,mostly increasing from 2017 to reaching a peak in 2018 and then falling back.And then stabilized with the domestic average level.1 393 strains were sensitive to Imipenem,and the sensitivity rate of Meropenem in this part was 96.2%.1 451 strains were sensitive to Imipenem,and 89%of them were sensitive to Meropenem at the same time.369 strains were both resistant to Imipenem and Meropenem,and 33.1%of them were sensitive to Ceftazidime.The more resistant to β-lactam,the lower the sensitivity rate to Amikacin and Ciprofloxacin.Conclusion The overall drug sensitivity of PA in this hospital is relatively good.Should adhere to strict management of antibiotic use.Aminoglycosides can be the preferred drugs for empirical treatment,followed by Quinolones,and Carbapenems and Ceftazidime are also candidates.PA has diverse resistance mechanisms to β-lactam antimicrobials,and carbapenem-resistant strains can be mediated by different mechanisms or jointly.

Objective: To preliminarily explore the mechanism of tensile stress regulating endochondral osteogenesis of condyle by analyzing the expression profiles of significantly different microRNAs (miRNAs) in exosomes of rat mandibular condylar chondrocytes (MCC) under quiescent and cyclic tensile strain (CTS) conditions. Methods: Rat condylar chondrocytes were cultured under static and CTS conditions respectively (10 SD rats, male, 2 weeks old), and exosomes were extracted. The two groups of exosomes were named as control group and CTS group respectively. The differential expression miRNAs were screened by high-throughput sequencing. Bioinformatics analysis and prediction of target genes related to osteogenesis were performed by TargetScan and miRanda website. Results: The exosomes of rat condylar chondrocytes cultured under tensile stress showed a "double concave disc" monolayer membrane structure, the expression of CD9 and CD81 were positive, and the particle size distribution accorded with the characteristics of exosomes, which was consistent with that of static cultured rat condylar chondrocytes. A total of 85 miRNAs with significantly different expression were detected by high-throughput sequencing (P<0.05). The main biological processes and molecular functions of differential miRNAs were biological processes and protein binding, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathway enrichment analysis showed that there was significant enrichment in mammalian target of rapamycin (mTOR) signal pathway. The candidate target genes of miR-199a-5p include bone morphogenetic protein 3 (BMP3), endothelin converting enzyme 1, and miR-186-5p may target Smad8 and BMP3 to exert osteogenesis-related functions. Conclusions: Compared with static state, tensile stress stimulation can change the expression of miRNAs such as miR-199a-5p, miR-186-5p in the exocrine body of rat condylar chondrocytes, which can be considered as a mean to regulate the application potential of the exosomes.
Animals ; Male ; Rats ; Bone Morphogenetic Protein 3 ; Chondrocytes/metabolism* ; Mandibular Condyle ; MicroRNAs/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Stress, Mechanical

Objective:To investigate the clinical features of direct and indirect carotid cavernous fistulas (CCFs).Methods:Patients with CCF treated in the Affiliated Hospital of Xuzhou Medical University from January 2010 to August 2020 were enrolled retrospectively. Relevant clinical data were collected, including the main clinical manifestations, neuroimaging features, and treatment methods. The clinical features of direct and indirect CCFs were compared.Results:A total of 31 patients were enrolled in the study, 29 (93.5%) had ocular symptoms, of which conjunctival hyperemia and edema ( n=24, 77.4%), exophthalmos ( n=19, 61.3%) and orbital murmur ( n=18, 58.1%) were most common. There were 23 patients (74.2%) in direct CCF group and 8 (25.8%) in indirect CCF group. The former had more history of head trauma (78.2% vs. 12.5%; P=0.002), more flow volume (high-flow CCFs: 100% vs. 37.5%; P<0.001) and more likely to cause orbital murmur (69.6% vs. 25.0%; P=0.043). Endovascular embolization was safe and effective. The common methods of endovascular embolization were EVAL glue combined with coil embolization ( n=18, 66.7%) and detachable balloon embolization alone ( n=6, 22.2%). Conclusion:Ocular manifestations are most prominent in patients with CCFs. Direct CCF is more common, usually with a history of head trauma, and the clinical and imaging features are more typical. Interventional embolization is the preferred treatment option for patients with CCF.

Objective:To investigate the relationship of papillary thyroid microcarcinoma (PTMC) with serum thyroglobulin.Methods:Data of 539 patients with papillary thyroid nodule (≤1cm) in Department of Thyroid and Breast Surgery of the Second Hospital of Anhui Medical University and the Department of Oncology Surgery of Suzhou Municipal Hospital for thyroidectomy were retrospectively analyzed. All of the nodules were classified as TI-RADS 4b with ultrasound. According to the postoperative pathological results, patients were divided into PTMC group (experiment group) and benign tumor group (control group) . The PTMC patients were also divided into lymph node metastasis group (experiment group) and no lymph node metastasis group (control group) based on the cervical lymph node metastasis. Then we analyzed the relationship between thyroid stimulating hormone (TSH) , thyroglobulin antibody (TgAb) , thyroid peroxidase antibody (TPOAb) and thyroglobulin (Tg) with PTMC and lymph node metastasis by SPSS.Results:Age, TSH, Tg and TgAb were independent risk factors for PTMC, B: -0.020, 0.192, 0.026, 0.008, 95% CI: 0.962-0.998, 1.045-1.404, 1.015-1.038, 1.003-1.014, both P<0.05. The relations between PTMC and TSH, Tg and TgAb were positive, while age was in negative correlation with PTMC. Meanwhile, age and thyroglobulin (Tg) were also independent risk factors for lymph node metastasis in PTMC patients, B: -0.025, 0.014, 95% CI: 0.957-0.994, 1.008-1.021, both P<0.05. Age was negatively correlated with lymph node metastasis and Tg was positively correlated with lymph node metastasis. Tg level higher than 26.520 ng/ml indicated that the nodule was PTMC (sensitivity: 0.560, specificity: 0.719) , and Tg level higher than 36.695 ng/ml predicted lymph node metastasis in PTMC patients (sensitivity: 0.532, specificity: 0.788) . Conclusion:Tg is a sensitive serum index for identifying PTMC from benign thyroid nodule, and it is also related to lymph node metastasis in PTMC patients.

Objective: To investigate the short-term clinical efficacy of laparoscopic common bile duct exploration(LCBDE) with primary suture or T tube drainage in the management of choledocholithiasis. Methods: The retrospective cohort study was conducted from January 2014 to December 2018 with the clinical data of patients with choledocholithiasis being analyzed. A total of 863 patients were enrolled in this study. There were 431 males and 432 females. The median age was 60 (range 11 to 94). These patients had received LCBDE with primary suture (n=287) and T tube drainage (n=576) in the Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University. Observation indicators: (1)Preoperative blood biochemistry, including blood serum levels of total bilirubin, direct bilirubin, ALT, AST, GGT. (2) Intraoperative conditions, including operation time, blood loss, diameter of common bile duct, number of common bile duct stone.(3)Short-term postoperative conditions, including postoperative hospital stay, postoperative complications. Measurement data with non-normal distribution were described as M (P₂₅, P₇₅), and comparison between groups was done using Mann-Whitney U test. Comparison of count data between groups were analyzed using the chi-square test. Univariate analysis and subsequent multivariable logistic regression were used to investigated the factors affecting the selection of surgical methods. Results: (1) Blood serum levels of total bilirubin and direct bilirubin in the T tube drainage group were 17.0(12.2, 36.0) μmol/L, 7.6(4.9, 19.0) μmol/L, which were significantly higher than those of the primary suture group[15.7(11.8, 29.7) μmol/L, 6.7(4.4, 16.5) μmol/L)](Z=-2.023, -2.468, P<0.05). Preoperative blood serum levels of ALT, AST and GGT in the T tube drainage group were 56.7 (26.6, 128.8) U/L, 38.0(24.3, 75.8) U/L and 179.7(50.8, 394.4) U/L, the primary suture group were[68.2(24.8, 165.3) U/L, 35.5(22.8, 96.9) U/L and 235.2(74.9, 459.1) U/L], with no difference between the two groups (Z=-0.985, -0.437, -1.740, P>0.05). (2)The operation time of the primary suture group was 85(70, 100) min, which was significantly shorter than that of the T tube drainage group[97(75, 120) min](Z=-5.532, P<0.05). The diameter of common bile duct in the primary suture and T tube drainage group were 1.0(0.8, 1.2) cm and 1.0(0.8, 1.2) cm, respectively. Significant difference was observed between the two groups(Z=-2.071, P<0.05). The intraoperative blood loss in the primary suture and T tube drainage group were 20(10, 50) ml and 20(20, 50) ml, with no difference between the two groups (Z=-0.477, P>0.05). 61.32%(176/287) and 67.36%(388/576) of patients in the primary suture group and T tube drainage group were found with multiple stones in the common bile duct, with no difference between the two groups (χ²=3.083, P>0.05). (3)The primary suture group showed shorter postoperative hospital stay compared with the T tube drainage group[4(3, 5) d vs 6(5, 6) d, Z=-12.057, P<0.05]. The primary suture group showed more patients with bile leakage (2.09%) compared with that of the T tube drainage group (0.35%). Multivariable logistic regression showed that the number of common bile duct stone, diameter of common bile duct, time period of surgery, surgery group were significant factors affecting the selection of surgical methods(OR=1.687, 2.423, 0.587, 4.632, 95%CI: 1.152-2.470, 1.519-3.865, 0.511-0.675, 3.698-5.802, P<0.05). Conclusions Although different surgeons showed different opinions with the method of primary suture, laparoscopic common duct exploration with primary suture is safe and reliable in the management of choledocholithiasis with shorter operation time and faster postoperative recovery. T tube drainage is not absolutely necessary in the management of choledocholithiasis. Patients with multiple common bile duct stone or large diameter of common bile duct are likely to receive T tube drainage.

This present study is to develop an HPLC method for simultaneous determination of four diester diterpenoid alkaloids, beiwutine, mesaconitine, hypaconitine and aconitine in the leaves of Aconitum kusnezoffii, so as to provide evidence of the quality control of this herb. The four constituents were measured on a Waters XBridge CC₁₈ column(4.6 mmχ250 mm, 5 μm). The mobile phase was acetonitrile-40 mmol·L⁻¹ ammonium acetate solution(adjusted pH to 10.5 with ammonia solution)(33:67) with isocratic elution at a flow rate of 1.0 mL·min⁻¹; the detection wavelength was 235 nm; the column temperature was 30 °C, and the injection volume was 10 μL. Next, this contents of the four diester diterpenoid alkaloids in 12 samples were 0.025 5-0.088 5, 0.039 1-0.071 5, 0.026 6-0.081 0 and 0.008 12-0.031 2 mg·g⁻¹, respectively. Next, this method has been successfully applied to the analysis of A. kusnezoffii folium in different harvest periods. The contents of the four alkaloids decreased primarily, and then increased with the postponing of harvest. The established method is proved to be accurate and sensitive for the determination of alkaloids in A. kusnezoffii folium, and may be useful for the quality improvement of this herbal medicine. Moreover, these results indicated the scientific significance for the toxicity and the suitable harvest time of this herb.
Aconitine ; analysis ; Aconitum ; chemistry ; Chromatography, High Pressure Liquid ; Diterpene Alkaloids ; analysis ; Drugs, Chinese Herbal ; chemistry ; Phytochemicals ; analysis ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry

Objective To evaluate the effects of turmeric volatile oil (TVO) combined with cisplatin on the proliferation and apoptosis of a human cutaneous squamous cell carcinoma cell line A431,and to explore their mechanisms.Methods Some cultured A431 cells at exponential growth phase were divided into several groups to be treated with 5,10,20,40 and 80 mg/L TVO,as well as high-glucose Dulbecco's modified Eagle's medium (DMEM) containing 1％ dimethyl sulfoxide (DMSO,control group),respectively.After 24-hour treatment,cell counting kit 8 (CCK8) assay was performed to estimate the proliferative activity of A431 cells in the above groups.Some other A431 cells were divided into 4 groups:control group treated with high-glucose DMEM containing 1％ DMSO,TVO group treated with 40 mg/LTVO,cisplatin group treated with 10 mg/L cisplatin,and TVO + cisplatin group treated with 40 mg/L TVO and 10 mg/L cisplatin.After 24-hour treatment,CCK8 assay was performed to estimate the cellular proliferative activity,inverted microscopy to observe changes in cell morphology,fluorescence microscopy to detect cell apoptosis after acridine orange (AO)/ethidium bromide (EB) double-staining,colorimetry to evaluate the activity of Caspase-3 and Caspase-9,and Western blot analysis to determine the protein expression of Caspase-3 and p-glycoprotein.Results After 24-hour treatment with 5,10,20,40 and 80 mg/L TVO,the cell proliferation rates were inhibited by (12.83 ± 6.4)％,(16.27 ± 11.4)％,(21.61 ± 9.1)％,(33.11 ± 2.0)％ and (46.00 ± 3.3)％ respectively,and the inhibition rates were all significantly higher in these groups than in the control group (4.03％ ± 1.4％,all P ＜ 0.05).The 50％ inhibitory concentration (IC50) of TVO at 24 hours was (61.66 ± 1.03) mg/L.Compared with the control group,the proliferation inhibition rates significantly increased in the TVO group,cisplatin group and TVO + cisplatin group (all P ＜ 0.05),suggesting that the combination of TVO and cisplatin showed synergistic inhibitory effects with a combination index of 1.366.Moreover,A431 cells turned round to different extents and became apoptotic in the TVO group and cisplatin group,and the TVO + cisplatin group showed obviously decreased number of cells and a large number of cell debris.The TVO + cisplatin group also showed significantly increased activity of Caspase-3 (1.520 ± 0.115) and Caspase-9 (2.760 ± 0.297) as well as protein expression of Caspase-3 (1.482 ± 0.016) compared with the TVO group (Caspase-3 activity:1.117 ± 0.095;Caspase-9 activity:1.259 ± 0.059;Caspase-3 protein expression:1.156 ± 0.006,all P ＜ 0.01) and cisplatin group (Caspase-3 activity:1.381 ± 0.089;Caspase-9 activity:1.829 ± 0.171;Caspase-3 protein expression:1.296 ± 0.021,all P ＜ 0.01),but significantly decreased p-glycoprotein expression (0.528 ± 0.014) compared with the TVO group (1.311 ± 0.011,P ＜ 0.01) and cisplatin group (1.169 ± 0.012,P ＜ 0.01).Conclusion TVO combined with cisplatin can synergistically inhibit the proliferation of A431 cells and induce cell apoptosis,which may be associated with activation of the caspase system and decreased expression of pglycoprotein.

Objective To discuss the efficacy of laparoscopic ureteroureterostomy for upper pole hydronephro-sis and ureteral dilatation in children with complete duplex kidney.Methods The clinical data of 14 patients (15 units in total)who underwent laparoscopic ureteroureterostomy from April 2016 to October 2017 were retrospectively analyzed. Nine out of 14 cases had repeated urinary tract infections(UTI)and other symptoms[6 cases in group A:patients without vesicoureteral reflux(VUR)but presenting urinary tract infection (UTI)symptoms,3 cases in group C:patients diagnosed with VUR];5 cases of asymptomatic patients were selected as group B.All the 14 cases had upper pole hydronephrosis and ureteral dilatation.Preoperative examinations included ultrosonograpy,urinary magnetic resonance urography(MRU), intravenous pyelography (IVP),voiding cystourethrogram(VCUG),and nuclear renal scanning.It was found that 4 cases had ureterocele;3 cases had recurrent cystoureteral reflux (group C)before operation,and 1 case had cystoureteral re-fluxed after replantation.Results Laparoscopic surgery was successful in all of 14 children.None of them were shifted to open surgery because of abdominal viscera injury bleeding.The operation duration was 85－140 min.The average posto-perative hospital stay was 5.58 days.There was neither urinary anastomotic leakage nor UTI.Fourteen cases were followed up and the postoperative follow－up period was 7－23 months.No cases developed urinary tract infection except 2 cases with vescioureteral reflux.Ultrasound examination showed that the upper renal parenchyma of 5 children was thicker,ul-trasonography showed that upper pole hydronephrosis was better and ureteroceles were smaller.There was no complication such as lower pole hydronephrosis.The symptoms of urinary tract infection disappeared after operation.Conclusions Laparoscopic ureteroureterostomy can treat renal duplication with less trauma,and it is safe and effective.It can be one of therapeutic regimen to treat low－functional upper pole hydronephrosis and ureteral dilatation in renal duplication.Howe-ver,this procedure cannot be used for vescoureteral reflux cases because of high rate of stump infection.

Objective To analyze the prognostic factors of adrenal tumor in children under 12 years of age. Methods A total of 90 children with 97 adrenal tumors admitted from June 2006 to August 2017 were selected in Children's Hospital of Nanjing Medical University.The age distribution,tumor type,biochemistry and tumor indicators, treatment,stage classification and prognosis were analyzed.Results There were 46 males and 44 females in 90 cases. Ages ranged from 4 days to 11 years and 1 month,with an average of (38.1 ± 31.3)months.The main clinical mani-festations were abdominal mass,fever and abdominal pain.Eighty cases (82.5%)underwent surgery,while 17 cases (17. 5%)did not.Open resection was performed in 48 cases,open partial resection in 11 cases,laparoscopic surgery in 10 cases,and just biopsy in 11 cases.The pathological examination showed 43 cases with neuroblastoma,13 cases with ganglioneuroblastoma,8 cases with ganglioneuroma,5 cases with adrenocortical carcinoma,3 cases with teratoma,1 case with pheochromocytoma,1 case with malignant rhabdoid tumor.Statistical analysis revealed that neuron－specific eno-lase(NSE)value of neuroblastoma and lactate dehydrogenase(LDH)value of cortical cancer increased significantly. The age was correlated with tumor stage,and patients had older age on stage Ⅳ.Complete resection in surgery was correlated with the stage of the tumor,as tumor in lower tumor stage seemed easier to be completely removed.Fifty－three cases (58.9%)were followed up for 2 months up to 11 years and 4 months.Forty－four cases survived and 9 ca-ses died.Higher tumor stage predicated worse prognosis.Conclusions Adrenal gland tumors need early diagnosis and active treatment.Earlier onset of age,complete surgical resection with patients have better prognosis.Complete resection of the disease was a key factor in the prognosis.