Effectiveness and safety of dermal matrix used for diabetic foot ulcer: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Diabetic foot ulcers (DFUs) have become a global health concern, which can lead to diabetic foot infection (DFI), lower leg amputation, and even mortality. Though the standard of care (SOC) practices have been recognized as the "gold standard" for DFU care, SOC alone may not be adequate to heal all DFUs and prevent their recurrence. The use of dermal matrix has emerged as an adjuvant treatment to enhance DFU healing. The current study aimed to evaluate the effectiveness and safety of dermal matrix application as an adjuvant treatment to the SOC. METHODS: The databases of PubMed, Embase and CENTRAL were independently searched by two authors, with the following key terms: "diabetic foot ulcer", "acellular dermal matrix", "wound healing", and so on. Randomized controlled trials (RCTs) evaluated the efficacy and safety of dermal matrix in the treatment of DFUs were eligible for inclusion. The primary outcomes analyzed included time to complete healing and complete healing rate at the final follow-up, while secondary outcomes included wound area, ulcer recurrence rate, amputation risk and complication risk. Meta-analyses were performed using random-effect or fixed-effect models, based on the heterogeneity test. RESULTS: This study included a total of 15 RCTs with a total of 1524 subjects. Of these, 689 patients were treated with SOC alone, while 835 patients received SOC plus dermal matrix. Compared to the SOC group, significantly shorter time (MD = 2.84, 95%CI: 1.37 ~ 4.32, p < 0.001***) was required to achieve complete healing in dermal matrix group. Significantly higher complete healing rate (OR = 0.40, 95%CI: 0.33 ~ 0.49, p < 0.001***) and lower overall (RR = 1.83, 95%CI: 1.15 ~ 2.93, p = 0.011*) and major (RR = 2.64, 95%CI: 1.30 ~ 5.36, p = 0.007**) amputation risks were achieved in dermal matrix group compared to SOC group. No significant difference was found in the wound area, ulcer recurrence rate, and complication risk between the two groups. CONCLUSIONS: The application of dermal matrix as an adjuvant therapy in conjunction with SOC effectively improved the healing process of DFUs and reduced the amputation risk when compared to SOC alone. Furthermore, dermal matrix application was well tolerated by the subjects with no added complication risk.

Feasibility of contrast-enhanced ultrasound and flank position during percutaneous nephrolithotomy in patients with no apparent hydronephrosis: a randomized controlled trial.

PURPOSE: To investigate the puncture accuracy and feasibility of contrast-enhanced ultrasound (CEUS) guided percutaneous nephrolithotomy (PCNL) in flank position for patients with no apparent hydronephrosis. METHODS: Between May 2018 and June 2020, 72 kidney stone patients with no or mild hydronephrosis were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided group. Patients' demographics and perioperative outcomes were compared, including the success rate of puncture via calyceal fornix, the success rate of a single-needle puncture, puncture time, operative time, postoperative hemoglobin loss, stone-free rate, incidence of complications and postoperative stay. RESULTS: The success rate of puncture via calyceal fornix for CEUS-guided group was significantly higher than that for conventional US-guided group (86.1 vs. 47.2%, p = 0.002). Patients performed with CEUS-guided PCNL required shorter renal puncture time than those guided with conventional US (36.5 s vs. 61.0 s, p < 0.001). The median postoperative hemoglobin loss in the CEUS-guided group was significantly lower than that in conventional US-guided group (2.5 vs. 14.5 g/L, p < 0.01). There was no statistically significant difference in the success rate of a single-needle puncture, operative time, stone-free rate, incidence of complications and postoperative stay between the two groups. CONCLUSION: CEUS guidance facilitates identification of the renal calyx fornix, and benefits more precise renal puncture and less hemoglobin loss in PCNL. CEUS-guided PCNL in flank position is a feasible approach to the treatment of kidney stone patients with no apparent hydronephrosis. TRIAL REGISTRATION NUMBER: ChiCTR1800015417.

Clinical outcomes and safety of osimertinib plus anlotinib for patients with previously treated EGFR T790M-positive NSCLC: A retrospective study.

WHAT IS KNOWN AND OBJECTIVE: Although osimertinib achieved convincing efficacy for patients with EGFR T790M-positive non-small-cell lung cancer (NSCLC) as second-line treatment in the AURA3 clinical trials, patients developed drug resistance ultimately. Therefore, the present study was to investigate the clinical outcome and safety of osimertinib plus anlotinib for patients with previously treated EGFR T790M-positive NSCLC. METHODS: Designed as a retrospective study, this study consecutively included a total of 33 patients with advanced NSCLC who possessed a EGFR T790M-positive mutation and progressed after the first-line therapy. Eligible patients were treated with osimertinib plus anlotinib. Baseline characteristics of the patients were collected during hospitalization. Efficacy of the combination regimen was assessed with the change of target lesion using imaging evidence according to RECIST 1.1 criteria, and all the patients were followed up regularly. Adverse reactions were collected and documented during the treatment. Univariate analysis according to baseline characteristic subgroups was performed using log-rank test, and multivariate analysis was carried out by Cox regression analysis. RESULTS AND DISCUSSION: The best overall response of the patients during osimertinib and anlotinib combination indicated that complete response was found in one patient, partial response was observed in 26 patients, stable disease was noted in 5 patients and progressive disease was reported in one patient. Therefore, objective response rate (ORR) of the combination regimen was 81.8% (95%CI: 64.5%-93.0%), and disease control rate (DCR) was 97.0% (95%CI: 84.2%-99.9%). Furthermore, the median progression-free survival (PFS) of the 33 patients with NSCLC was 15.5 months (95%CI: 6.19-24.81). In addition, the median overall survival (OS) of the 33 patients with NSCLC was 23.8 months (95% CI: 17.67-29.93). Safety profile suggested that the most common adverse reactions of the patients with NSCLC who received anlotinib plus osimertinib were hypertension (63.6%), fatigue (57.6%), diarrhoea (48.5%%), dermal toxicity (39.4%) and proteinuria (33.3%). Interestingly, multivariate Cox regression analysis for PFS demonstrated that ECOG performance status was an independent factor to predict the PFS of the combination regimen. WHAT IS NEW AND CONCLUSION: Osimertinib plus anlotinib regimen preliminarily exhibited encouraging clinical outcomes and acceptable safety profile for patients with previously treated EGFR T790M-positive NSCLC numerically. This conclusion should be validated in prospective clinical trials.

Implication of PD­L1 polymorphisms rs2297136 on clinical outcomes of patients with advanced NSCLC who received PD­1 blockades: A retrospective exploratory study.

Clinically, programmed death-1 (PD-1) blockades have demonstrated promising therapeutic outcomes for patients with advanced non-small cell lung cancer (NSCLC). The present study aimed to examine the impact of programmed death-ligand 1 (PD-L1) polymorphism on clinical outcomes of patients with advanced NSCLC who were treated with PD-1 blockades therapy. The present study was designed as a retrospective analysis, where a consecutive screening of 89 patients with advanced NSCLC who received PD-1 blockades monotherapy were screened. Biological specimens were collected to determine the presence of polymorphism and PD-L1 mRNA expression through genotyping. The analysis focused on examining the relationship between the genotype status of PD-L1 polymorphism and clinical outcomes. Among the 89 patients with advanced NSCLC, the use of PD-1 blockades monotherapy resulted in objective response rate (ORR) of 22.5%, a median progression-free survival (PFS) of 3.4 months [95% Confidence Interval (CI): 1.80-5.00) and a median overall survival (OS) of 11.3 months (95% CI: 7.93-14.67). The analysis of polymorphism indicated that only rs2297136 had clinical significance. Among the 89 patients with NSCLC, the prevalence of rs2297136 was as follows: A total of 58 cases (65.2%) had the AA genotype, 28 cases (31.5%) had the AG genotype and 3 cases (3.4%) had the GG genotype. This resulted in a minor allele frequency of 0.19, which was in consistent with Hardy-Weinberg Equilibrium (P=0.865). The correlation analysis between genotype status of rs2297136 and clinical outcomes indicated that patients with the AA genotype had an ORR of 19.0%, while those with the AG/GG genotype had an ORR of 29.0% (P=0.278). Additionally, the median PFS for the AA genotype was 2.95 months, compared with 5.30 months for the AG/GG genotype (P=0.038). Accordingly, median OS of the AA and AG/GG genotypes was 8.8 and 18.4 months, respectively (P=0.011). The mRNA expression of PD-L1 was significantly higher in patients with AG/GG genotype compared with those with AA genotype (P<0.001). In clinical practice, PD-1 blockades demonstrated promising effectiveness in treating patients with advanced NSCLC. The presence of the rs2297136 variant in PD-L1 gene could potentially be used as a biomarker to predict the clinical outcomes of PD-1 blockades.

[Neutral alpha-glucosidase activity is correlated with the location of epididymal obstruction in azoospermia men].

OBJECTIVE: To evaluate the correlation of neutral alpha-glucosidase in seminal plasma with the location of epididymal obstruction in azoospermia men. METHODS: We detected neutral alpha-glucosidase activity in the seminal plasma of 59 men with obstructive azoospermia followed by determining the location of epididymal obstruction by scrotal exploratory surgery. Then we analyzed the correlation between neutral alpha-glucosidase and the location of epididymal obstructive azoospermia. RESULTS: Among the total number of patients, there were 25 cases of bilateral cauda epididymal obstruction, 15 bilateral corpus, 12 bilateral caput, 4 unilateral caput-opposite cauda, and 3 unilateral corpus-opposite cauda. The neutral alpha-glucosidase levels in the seminal plasma of bilateral cauda, corpus and capus epididymal obstructions were (4.1 +/- 1.9), (13.8 +/- 4.4) and (46.8 +/- 19.3) mU per ejaculate, respectively, with statistically significant differences among the three groups (P < 0.05). CONCLUSION: Neutral alpha-glucosidase activity is significantly correlated with the location of epididymal obstruction in azoospermia men, which helps to locate epididymal obstruction, evaluate surgical prognosis and reduce the time of scrotal exploratory surgery.

[Effects of nonylphenol and cadmium on sperm acrosome reaction in vitro in mice].

OBJECTIVE: To study the effects of nonylphenol and cadmium on acrosome reaction in vitro in mouse spermatozoa. METHODS: Sperm were collected from the vas deferens of mice, capacitated in vitro and stimulated with A23187 at 30 micromol/L to induce acrosome reaction. Then the sperm suspension was treated with nonylphenol at 10, 20, 30, 60 and 100 micromol/L or cadmium at 500, 2500 and 5 000 micromol/L, and the control group treated with the carrier solvent. Acrosome reaction of the sperm was analyzed by FITC-PSA staining. RESULTS: Compared with the control group, nonylphenol significantly inhibited acrosome reaction at the concentration of > 60 micromol/L (P < 0.01), but not at < 30 micromol/L (P > 0.05), and the sperm survival rate was reduced with increased concentration of nonylphenol. However, cadmium exhibited no significant influence on either acrosome reaction (P > 0.05) or sperm survival rate at 500 - 5 000 micromol/L. CONCLUSION: Nonylphenol and cadmium affect the spermatogenesis of mice in different ways; the former directly inhibits sperm acrosome reaction, while the latter has no direct effect on it.

Efficacy and Safety of Anlotinib Monotherapy as Third-Line Therapy for Elderly Patients with Non-Small Cell Lung Cancer: A Real-World Exploratory Study.

PURPOSE: The present study was to investigate the real-world efficacy and safety of anlotinib monotherapy as third-line therapy for elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 83 elderly patients (>65 years) with NSCLC who were progressed at least two lines of previous systemic therapy were recruited retrospectively. Patients were treated with anlotinib monotherapy (12 mg or 10 mg). Efficacy of anlotinib was assessed and all the patients were followed up regularly. Adverse reactions were collected during anlotinib administration. Univariate analysis was performed using Log rank test and multivariate analysis was adjusted by Cox regression analysis. Additionally, prognostic analysis according to common adverse reactions was implemented to identify the potential clinical significance. RESULTS: The best overall response of the 83 elderly patients during anlotinib monotherapy indicated that partial response (PR) was observed in six patients, stable disease (SD) was noted in 59 patients, and progressive disease (PD) was reported in 18 patients. Consequently, the objective response rate (ORR) was 7.2% (95% CI=2.7-15.1%) and the disease control rate (DCR) was 78.3% (95% CI=67.9-86.6%). The median progression-free survival (PFS) of the 83 elderly patients with NSCLC was 4.2 months (95% CI=3.51-4.89). Furthermore, the median overall survival (OS) of the 83 patients was 9.6 months (95% CI=6.65-12.55). The safety profile suggested that the relatively common adverse reactions of the elderly patients with ES-SCLC receiving anlotinib therapy were hypertension (49.4%), fatigue (45.8%), and hand-foot syndrome (39.8%). Interestingly, association analysis exhibited that the median PFS of patients with hypertension and non-hypertension was 4.5 and 3.0 months, respectively (χ 2=6.306, P=0.012). CONCLUSION: Anlotinib monotherapy demonstrated a satisfactory efficacy and tolerable safety profile in third-line settings for elderly patients with advanced NSCLC. Patients who experienced a hypertension adverse reaction induced by anlotinib therapy might confer superior PFS. The conclusion should be validated in prospective clinical trials subsequently.

Kidney xenotransplantation: Recent progress in preclinical research.

Kidney transplantation is the most effective treatment for end-stage renal disease, but is limited by the increasing shortage of deceased and living human donor kidneys. Xenotransplantation using pig organs provides the possibility to resolve the issue of organ supply shortage and is regarded as the next great medical revolution. In the past five years, there have been sequential advances toward the prolongation of life-supporting pig kidney xenograft survival in non-human primates, with the longest survival being 499 days. This progress is due to the growing availability of pigs with multi-layered genetic modifications to overcome the pathobiological barriers and the application of a costimulation blockade-based immunosuppressive regimen. These encouraging results bring the hope to initiate the clinical trials of pig kidney transplantation in the near future. In this review, we summarized the latest advances regarding pig kidney xenotransplantation in preclinical models to provide a basis for future investigation and potential clinical translation.

[Soluble proteins of the plerocercoid of Spirometra mansoni].

OBJECTIVE: To analyze soluble proteins of the plerocercoid of Spirometra mansoni. METHODS: The total protein of the plerocercoid of S. mansoni was separated by SDS-PAGE and two-dimensional electrophoresis (2-DE). Western blotting was performed to find out distinct antigens by sera of plerocercoid-infected mice. RESULTS: A total of 33 protein bands were separated by SDS-PAGE (Mr 13,800-145,400). Four of them were high-abundance proteins with Mr 26,500, Mr 37,600, Mr 88,200, and Mr 130,200, respectively. At least two protein bands of Mr 31,600 and 37,600 reacted with the infected mice sera. 367 protein spots were detected on 2-DE gel, among which. about 67% proteins were found within Mr 18,840-46,800 and isoelectric point (pI) 4-7. Western blotting showed 30 antigen spots specifically reacting with sera from mice infected by S. mansoni. CONCLUSION: Two protein bands and thirty protein spots are specific acidic proteins of S. mansoni plerocercoid.

Flexible ureteroscopy and laser lithotripsy for renal stones 2 cm or greater: A single institutional experience.

With improvements in endoscopy and laser technology, flexible ureteroscopy (FURS) has been a viable treatment option for large renal stones. Here, we share our experience of the FURS treatment for renal stones 2 cm or greater.We evaluated 251 consecutive patients who underwent FURS and holmium laser lithotripsy for renal stones 2 cm or greater between January 2015 and April 2019. Stone size was defined as the longest axis on non-contrast computed tomography. Data were retrospectively collected from electronic medical records. Patient demographics, stone clearance rates and perioperative complications were evaluated.There were 165 male patients and 86 female patients with an average age of 46.9 years (range 22-80 years). Mean stone size was 2.7 cm and the average number of procedures was 1.4 (range 1-5). The stone-free rate at the end of the first, second and third procedure was 61.9%, 82.9%, and 89.5%, respectively. The final stone-free rate decreased as stone size grows, and it was only 58.3% for kidney stones larger than 4 cm after an average of 2.3 procedures. The lowest clearance rates were observed in lower calyx calculi (87.2%) and multiple calyx calculi (83.5%). The overall complication rate was 15.1%, and the most common complication was postoperative fever (9.6%). One patient required blood transfusion, owing to postoperative coagulation disorders induced by urosepsis.Single or staged FURS is a practical treatment option for the renal stones sized 2 to 4 cm with acceptable efficacy and safety. Stone clearance rate of FURS treatment is mainly affected by stone size and location.

Construction and identification of Complex DNA vaccine of hepatitis B and Toxoplasma gondii.

OBJECTIVE: To construct and identify multi-gene recombinant expression vector pcDNA3-HBsAg-p30-ROP2. METHOD: Primers were designed according to the gene sequences of restriction enzyme cutting site of recombinant pcDNA3-p30-ROP2 and hepatitis B surface antigen (HBsAg). The target fragment of HBsAg was amplified and cloned to expression vector pcDNA3-p30-ROP2 by restriction enzyme digestion and ligation. The recombinant expression vector pcDNA3-HBsAg-p30-ROP2 was identified by PCR detection, followed by enzyme restriction and sequencing. RESULTS: The target fragment of HBsAg was successfully amplified, and the multi-gene eukaryotic expression vector pcDNA3-HBsAg-p30-ROP2 was established. PCR detection and restriction enzyme digestion showed that the length of the target fragment was consistent with the theoretical value. The recombinant expression vector contained the complete sequences of p30-ROP2 compound gene and HBsAg. CONCLUSION: Multi-gene recombinant expression vector pcDNA3-HBsAg-p30-ROP2 was successfully established. The constructed expression vector could be used to develop multi-gene nucleic acid vaccines.

[Studies on dihydrotestosterone-binding capacity in prostate tissue].

OBJECTIVE: To explore the effect of the binding ability of the dihydrotestosterone(DHT) in prostate. METHODS: Twenty-two normal prostate tissues taken from accident-death corpses without serious diseases, and cytosolic and nuclear fractions were prepared with all the endogenous hormone removed from the cytosolic and nuclear fractions by ether stripping. The content of the bound 3H-DHT was assayed by adding 3H-DHT. RESULTS: The average DHT-binding capacity of the DHT-binding protein in prostate was (0.0263 +/- 0.0047) nmol/g wet tissue. The DHT-binding capacities of cytosolic and nuclear fractions were (0.0103 +/- 0.0015) nmol/g wet tissue and (0.0155 +/- 0.0035) nmol/g wet tissue respectively, and the difference between them was very significant(P < 0.01). CONCLUSIONS: The DHT-binding capacity of the DHT-binding protein in prostate is high and maintaining the high DHT level facilitates the effect of DHT.

Multiple advanced surgical techniques to treat acquired seminal duct obstruction.

The aim of this study was to evaluate the outcomes of multiple advanced surgical treatments (i.e. microsurgery, laparoscopic surgery and endoscopic surgery) for acquired obstructive azoospermia. We analyzed the surgical outcomes of 51 patients with suspected acquired obstructive azoospermia consecutively who enrolled at our center between January 2009 and May 2013. Modified vasoepididymostomy, laparoscopically assisted vasovasostomy and transurethral incision of the ejaculatory duct with holmium laser were chosen and performed based on the different obstruction sites. The mean postoperative follow-up time was 22 months (range: 9 months to 52 months). Semen analyses were initiated at four postoperative weeks, followed by trimonthly (months 3, 6, 9 and 12) semen analyses, until no sperm was found at 12 months or until pregnancy was achieved. Patency was defined as >10,000 sperm ml⁻¹ of semen. The obstruction sites, postoperative patency and natural pregnancy rate were recorded. Of 51 patients, 47 underwent bilateral or unilateral surgical reconstruction; the other four patients were unable to be treated with surgical reconstruction because of pelvic vas or intratesticular tubules obstruction. The reconstruction rate was 92.2% (47/51), and the patency rate and natural pregnancy rate were 89.4% (42/47) and 38.1% (16/42), respectively. No severe complications were observed. Using multiple advanced surgical techniques, more extensive range of seminal duct obstruction was accessible and correctable; thus, a favorable patency and pregnancy rate can be achieved.

[Cultivation and isolation of bacteria coupling nitrogen removal from wastewater and hydrogen sulfide removal from biogas].

It was studied that during the startup of reactors the crucial bacteria coupling nitrogen removal from swine wastewater and hydrogen sulfide removal from biogas using bubbling absorption reactors without seeding sludge, with seeding anaerobic sludge and aerobic sludge, respectively. During the prophase of the experiment (before the 26th d), the removal rate of nitrogen and hydrogen sulfide were from 50% to 64% in reactors with seeding sludge, that in the reactor without seeding sludge was only 11%-14%. At the end of experiment (the 56th d after startup), the removal rates of nitrogen for three reactors were about 90%. The removal rates of hydrogen sulfide were more than 70%. The result showed that though the finishing time for startup of the reactor without seeding sludge was longer than that with seeding sludge, it could be obtained the same effect of removal of nitrogen and hydrogen sulfide as the latter after two months cultivation. In the different period of startup of the reactors, the variation of the population of bacteria was studied, which had the same trend as the removal effect of nitrogen and hydrogen sulfide. Two strains which could remove the nitrogen and hydrogen sulfide more than 60% simultaneously were isolated from the three reactors, and primarily identified as Thiobacillus denitrificans and Pseudomonas respectively, based on their morphology and physiological characters.