The applications of targeting gene delivery systems in tumor therapy have attracted extensive attention of researchers in recent years, as they can selectively deliver the therapeutic gene to tumor sites, improve the success rate of gene therapy and reduce the side effects. Therefore, design and development of novel gene delivery vehicles have been a hot area of current research. Recent studies have shown that mesenchymal stem cells (MSCs) have the ability to migrate towards and engraft into the tumor sites. Therefore, these properties make them a great hope for efficient targeted-delivery vehicles in cancer gene therapy. In this review, we examine the promising of utilization of MSCs as a targeted-delivery vehicle for cancer gene therapy, and summarize various challenges and concerns regarding this therapy.

There are lack of specific treatment for diabetic peripheral neuropathy (DPN)right now.However, TCM intervention highlights the distinct advantage for the disease.Modified Huangqi-Guizhiwuwu Tang is one of the important recipes for that.But there are no uniform standards curative effect evaluation for it, and some clinical trials do not have some new evaluation standards.We summary the clinical research literatures in recent years and analyze the existing problems, therefore, provide new recommendations as views for medical researchers in the design of clinical trials.

Objective To evaluate the clinical effect of the homemade traditional Chinese medicine bathing prescription combined with Thymalfasin and Isotretinoin treatment for Verruca Plantaris.Methods A total of 120 patients with Verruca Plantaris were randomly divided into 3 groups according to the random number table method (each group 40). The drug therapy group was given Thymalfasin and Isotretinoin to treatment; and the Chinese medicine washing group was given traditional Chinese medicine wash-out on the basis of drug therapy; and the physical therapy group was given liquid nitrogen freezing treatment on the basis of drug therapy. All the groups were treated 12 weeks and follow-up 3 months. Four weeks were a course, and a total of 3 courses. After the treatment, the symptom grading scores (number of skin lesions, the size of skin lesions, the degree of pain and the quality of life) was compared, and the clinical effect rate was evaluated and the recurrence rate was observed.Results Twelve weeks after treatment, Chinese medicine washing group total effective rate was 97.5% (39/40), drug treatment group 87.5% (35/40), and physical treatment group 90.0% (36/40). The Chinese medicine washing group total effective rate was superior to the drug therapy and physicaltherapy groups (Z values were -3.463,-3.122,P values were 0.001, 0.002). after treatment, the number of lesions scores (2.0 ± 1.1 vs. 2.8 ± 1.5, 2.7 ± 1.6,F=3.787), the size of the lesion scores (2.3 ± 1.7 vs. 3.2 ± 1.3, 3.1 ± 1.3, F=4.657), pain degree and the quality of life scores (0.4 ± 0.5 vs. 1.0 ± 1.2, 1.0 ± 1.0,F=5.353) in the Chinese medicine washing group were significantly higher than those in the drug therapy and physical therapy groups (P<0.01). After follow-up period, the recurrence rate of Chinese medicine washing group was 10.3% (4/39), the drug treatment group 25.7% (9/35), the physical therapy group 41.7% (15/36). The difference among 3 groups was statistically significant (Z=-3.188,P<0.01).Conclusions The traditional Chinese medicine combined with Thymalfasin and Isotretinoin could reduce the number of skin lesions, narrow the range of skin lesions and reduce the degree of pain, and improve the quality of life.

Objective To summarize our experience in robotic-assisted laparoscopic surgery for adrenal diseases Methods The clinical data of 243 patients with adrenal tumor treated by robotic-assisted laparoscopic surgery from March 2010 to February 2017 were retrospectively reviewed.There were 99 men and 144 women.The mean age was 51.6 years (range, 19-84).Tumors located at left adrenal in 140 cases, right in 97 cases,and both sides in 6 cases.The average diameter was 3.32 cm (range, 0.8-12 cm).However, there were 41 cases whose tumor diameter were greater than 5 cm.Results There were 2 cases of conversion during operation, 1 case converted to open surgery and the other to the traditional laparoscope surgery.The mean operative time was 35 min (range, 20-130 min).Estimated blood loss was 80 ml (range,20-1 200 ml).Blood transfusion was needed in 6 cases.The mean postoperative hospital stay was 5d (range, 3-20 d).The pathological diagnosis included 37 cases of pheochromocytoma, 149 cases of cortical adenoma, 3 cases of cortical carcinoma, 5 cases of metastatic tumor, 9 cases of adrenal myelolipoma, 3 cases of adrenal cyst, 2 cases of bronchogenic cyst, 25 cases of adrenal nodular hyperplasia,2 cases of angiomyolipomas, 1 case of mature teratoma, 1 case of diffuse large B-Cell lymphoma, 1 case of angioma, and 4 cases of neurofibromatosis.Conclusions Robotic-assisted laparoscopic adrenalectomy was safe and effective.Robotic-assisted laparoscopic surgery has the advantages over laparoscopic surgery in treatment of complicated adrenal tumor, such as large adrenal tumors, pheochromocytoma, bilateral adrenal diseases, overweight and obese patients with adrenal diseases.

Due to good mechanical properties and biocompatibility, tissue engineering scaffolds have become the vital method for repairing and regenerating articular cartilage defects. With the continuous development of tissue engineering technology, many scaffolds preparation and formation methods have been developed and tested in the past decade, however, the preparation of ideal regenerative scaffolds remain controversial. As load-bearing tissue inside the body joints, the matrix structure and cell composition of articular cartilage are hierarchical, and there are several smooth natural gradients from the cartilage surface to the subchondral bone layer, including cell phenotype and number, specific growth factors, matrix composition, fiber arrangement, mechanical properties, nutrient and oxygen consumption. Therefore, in the design of regenerative scaffolds, it is necessary to achieve these gradients to regenerate articular cartilage in situ. In recent studies, many new biomimetic gradient scaffolds have been used to simulate the natural gradient of articular cartilage. These scaffolds show different mechanical, physicochemical or biological gradients in the structure, and have achieved good repair effects. The related articles on tissue engineering for the treatment of articular cartilage defects were retrieved by searching databases with key wordsarticular cartilage injury, cartilage repair and gradient scaffolds. In this work,the structural, biochemical, biomechanical and nutrient metabolism gradients of natural articular cartilage were studied and summarized firstly. Then, the latest design and construction of articular cartilage gradient scaffolds were classified. Besides that, the material composition (such as hydrogels, nanomaterials, etc.) and the preparation process (such as electrospinning, 3D printing, etc.) of grandient scaffolds were further enhanced. Finally, the prospect and challenge of biomimetic gradient scaffolds in cartilage engineering are discussed, which provides a theoretical basis for the successful application of gradient scaffolds in clinical transformation.

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) and karyotyping in the prenatal diagnosis for carriers of balanced translocations. METHODS: Clinical records of 135 amniocentesis samples of balanced translocation carriers undergoing simultaneous CNV-seq and karyotyping were analyzed. Chromosomal aberrations were defined as those can definitely lead to birth defects definitely, which included chromosomal numerical abnormality, large deletion/duplication and pathogenic copy number variations (pCNVs). RESULTS: The detection rates for karyotyping and CNV-seq were 4.44% (6/135) and 5.93% (8/135) respectively, and the latter had a detection rate of 1.48(2/135) higher than the former. A total of 68 fetal chromosomal translocations were detected by karyotying analysis. CONCLUSION For couples carrying a balanced translocation, simultaneous CNV-seq and karyotyping is conducive to the detection of fetal chromosomal abnormalities and genetic counseling.
Chromosome Aberrations ; Chromosome Disorders/genetics* ; DNA Copy Number Variations ; Female ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Translocation, Genetic

OBJECTIVE: To explore the genetic basis of three families with recurrence of non-immune hydrops fetalis (NIHF) but negative result by copy number variation sequencing (CNV-seq). METHODS: Amniotic fluid sample and/or abortive tissues of the fetuses were collected and subjected to CNV-seq analysis. Peripheral blood samples of the parents were also taken for trio whole exome sequencing (trio WES). RESULTS: Fetus 1 was found to harbor heterozygous c.976G>T(p.Glu326*) variant of the SOX18 gene in addition with compound heterozygous variants c.844C>T(p.Arg282Trp) and c.9472+1G>A of the RYR1 gene. The three variants were all inherited from its parents and have been associated with the etiology of NIHF. Based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, the c.976G>T variant of SOX18 gene and c.9472+1G>A of RYR1 gene were predicted to be pathogenic (PVS1+PM2+PP3+PP4, PVS1+PM2+PP3), and c.844C>T variant of RYR1 gene to be likely pathogenic (PM1+PM2+PP3). Fetus 2 was found to harbor compound heterozygous variants c.6682C>T(p.Gln2228*) and c.4373_4383del(p.Val1458Alafs*63) of the PIEZO1 gene. Both variants were also inherited from its parents and are associated with the etiology of NIHF. Based on ACMG standards and guidelines, both c.6682C>T and c.4373_4383del variants of PIEZO1 gene were predicted to be pathogenic (PVS1+PM2+PP4, PVS1+PM2). Fetus 3 was found to harbor compound heterozygous variants of the TTN gene c.29860G>C(p.Asp9954His) and c.21107A>T(p.Asp7036Val), which were respectively inherited from its parents. Both variants have been strongly associated with the phenotype, though the connection between the etiology of NIHF and variants of the TTN gene remains elusive. Based on ACMG standards and guidelines, the c.29860G>C and c.21107A>T variants of TTN gene were predicted to be likely pathogenic (PM1+PM2+PP3). CONCLUSION Trio WES can improve the diagnosis rate of NIHF with a negative result by CNV-seq. Considering the urgency of prenatal diagnosis, CNV-seq and trio WES should be carried out at the same time for fetuses with NIHF.
DNA Copy Number Variations ; Female ; Genomics ; Heterozygote ; Humans ; Hydrops Fetalis/genetics* ; Ion Channels ; Pregnancy ; SOXF Transcription Factors ; United States ; Whole Exome Sequencing

Objective To explore the clinical feasibility of robot-assisted laparoscopic radical cystectomy (RARC) with total intracorporeal othotopic ileal neobladder (TIOIN).Methods A consecutive series of 4 patients (2 male,2 female),who underwent RARC with TIOIN by a single surgeon,were included in the retrospective study,between March 2017 and June 2017.Their age ranged from 59 to 71 years,which the mean age was (65.7 ± 4.9) years.Preoperative urinary CT scan,cystoscopic examination and transurethral resection of bladder tumor were performed for diagnosis.Among these,2 patients underwent side-to-side bowel anastomosis using a linear stapler,while hand-sewn anastomosis was performed in the other 2 patients.The detubularized bowel segment was arranged in a U shape,and then the two medial borders were closed to create the posterior wall of the neobladder,which completed a partial U shape and anastomosed with the end of urethra.After placing the single J stents into the ureter,the uretero-neobladder was anastomosed.To close the urine reservoir,each border of the U-shaped segment was folded again and sutured to form a sealed pouch.Results All operations were performed successfully.The average operation time for RARC was 93.2 min (ranging 79-117 min).The average operation time for urinary diversion was 214.2 min (ranging 163-251 min).The mean estimated blood loss was 304.5 ml (ranging 200-400 ml).The mean hospital stay was 20.5 d (ranging 13-32 day).The number of dissected lymph node ranged from 11 to 16 (mean 3.7 ± 2.6).All the surgical margins were negative.The time for postoperative out-of-bed activity and bowel function recovery was 2-3 days and 3-4 days,respectively.The single-J stents were removed 1 months after operation,generally.No urine leakage was noticed after removing the drainage tube and catheter.The lymph leakage was observed in one case,which was resolved 15 days post-operatively after given nutrient therapy.The performance of urinary continence was satisfactory,except one patient complained about the nocturnal incontinence.After the regular pelvic exercise,the symptom improved two months after the operation.Hydronephrosis and intestinal leakage were not observed.Conclusions Our initial experience showed that RARC with TIOIN is feasible and alterative for experienced surgeon.

Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.
Antineoplastic Agents ; administration & dosage ; Doxorubicin ; administration & dosage ; Drug Delivery Systems ; Gene Transfer Techniques ; Humans ; Mesenchymal Stem Cells ; Neoplasms ; therapy ; Paclitaxel ; administration & dosage ; Research ; trends

Objective To explore the clinical efficacy and safety of off-clamping in robotic-assisted partial nephrectomy (RAPN) for the treatment of renal tumors.Methods From January 2015 to March 2017,the data of 48 patients who underwent off-clamping RAPN were reviewed retrospectively.There were 31 males and 17 females,and the mean age was 57 years (range:23-84 years).The mean tumor size was 3.1 cm (range:1.2-6.4 cm),with the upper,middle,and lower polar tumors account for 35.4％,27.1％,and 37.5％,respectively.The clinical tumor stage was T1N0M0 in all 48 cases,according to the AJCC tumor staging system for renal cancer.Results RAPNs were performed successfully in all 48 cases,without conversion to open surgery.In those patients,the application of off-clamping in robotic-assisted partial nephrectomy was performed in 44 cases.The renal artery and vein was exposed,dissected,isolated and then clamped in 4 cases due to bleeding.The mean surgical time was 85 min (range:75-185 min).The mean estimated blood loss was 134 ml (range:60-270 ml),and no blood transfusion was needed.The wound surface was closed using interrupted suture with Hem-o-lok clips securing each needle point.The mean time for renorrhaphy was 22 min (rang:11-31 min).No intraoperative severe complications such as vascular injury,trauma of abdominal organ occurred.There were 5 complications,including 2 cases of hematuria,2 cases of delayed healing of incision,and 1 case of pneumohypoderma.The pathological diagnosis included 40 cases of renal clear cell carcinoma,3 cases of papillary renal cell carcinoma,and 5 cases of angiomyolipomas.No tumor recurrence or distant metastasis was observed during the average follow-up of 17 months (range 3-27 months).Conclusions Off-clamping RAPN is safe and feasible approach to excise certain kidney tumors.It carries the benefits of less complication,quick recovery,and less ischemia reperfusion renal injury.Off-clamping RAPN would be suitable for those patients with solitary kidneys,renal insufficiency,and bilateral tumors.