Evaluating the efficacy and safety of perianal injection of liposomal ropivacaine HR18034 for postoperative analgesia following hemorrhoidectomy: A multicenter, randomized, double-blind, controlled phase II clinical trial.

STUDY OBJECTIVE: HR18034, composed of the ropivacaine encapsulated in multi-lamellar, concentric circular structure liposomes as the major component and a small amount of free ropivacaine, has performed well in animal experiments and phase I clinical trials. This trial was to investigate the efficacy, safety, pharmacokinetic profile and the minimum effective dose of HR18034 for postoperative analgesia after hemorrhoidectomy compared with ropivacaine. DESIGN: A multicenter, randomized, double-blind trial. SETTING: 19 medical centers in China. PATIENTS: 85 patients undergoing hemorrhoidectomy between October 2022 to November 2022. INTERVENTIONS: Patients were randomly divided into HR 18034 190 mg group, 285 mg group, 380 mg group and ropivacaine 75 mg group, receiving single local anesthetic perianal injection for postoperative analgesia. MEASUREMENTS: The primary outcome was the area under the resting state NRS score -time curve within 72 h after injection. The second outcomes included the proportion of patients without pain, the proportion of patients not requiring rescue analgesia, cumulative morphine consumption for rescue analgesia, etc. Safety was evaluated by adverse events incidence and plasma ropivacaine concentrations were measured to explore the pharmacokinetic characteristics of HR18034. MAIN RESULTS: The areas under the NRS score (at rest and moving states)-time curve were significantly lower in HR 18034 380 mg group than ropivacaine 75 mg at 24 h, 48 h, and 72 h after administration. However, this superiority was not observed in HR18034 190 mg group and 285 mg group. There was no difference in cumulative morphine consumption for rescue analgesia between HR 18034 groups and ropivacaine group. CONCLUSIONS: HR 18034 380 mg showed superior analgesic efficacy and equivalent safety compared to ropivacaine 75 mg after hemorrhoidectomy, thus preliminarily determined as minimum effective dose.

Efficacy and safety of 13 surgical techniques for the treatment of complex anal fistula, non-Crohn CAF: a systematic review and network meta-analysis.

BACKGROUND: Considering the difficulty of treating complex anal fistula (CAF), various surgical techniques exist in clinical work. However, none are ideal. Evidence on the efficacy and safety of different surgical treatments is scarce. The authors aimed to compare the outcomes of the 13 surgical techniques and tried to find the best surgical method for treating CAF. MATERIALS AND METHODS: The authors searched worldwide databases, including Pubmed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and SinoMed, from inception to March 2023. All randomized controlled trials comparing the outcomes of 13 surgical techniques were included according to the PICO principles. The indicators of the cure rate, the recurrence rate, the complication rate, the operating time, the postoperative pain on day 1 (VAS), and the postoperative incontinence in month 1 (Wexner) were extracted and analyzed using STATA software 15.1, Review Manager 5.4, and GeMTC14.3. RESULTS: Twenty-eight randomized controlled trials with a total of 2274 patients were included in the network meta-analysis. There was no statistically significant difference in the comparison among any surgical interventions in terms of the cure rate ( P >0.05 Table 2) and recurrence rate ( P >0.05 Table 3). However, in terms of complication rate, fistulectomy was lower than FPS (Median: 0.14; 95% CI: 0.02-0.70) or fistulotomy (Median: 0.09; 95% CI: 0.01-0.55), and fistulotomy was lower than EAFR (Median: 0.24; 95% CI: 0.05-0.84), LIFT (Median: 0.17; 95% CI: 0.02-0.66) or LIFT-EAFR (Median: 0.11; 95% CI: 0.01-0.69) ( P >0.05 Table 4). The surface estimated the advantages and disadvantages under the cumulative ranking (SUCRA). The ranking results indicated that fistulectomy might have the lowest complication rate (SUCRA=7.9%). Because the network results of the operating time, the postoperative pain, and the postoperative incontinence contained no closed loops, the results of their probability ranking could only be referenced, demonstrating that fistulectomy might have the shortest operating time (SUCRA=23.4%), video-assisted modified ligation of the intersphincteric fistula tract (VAMLIFT) might have the lowest postoperative pain on day 1 (VAS) (SUCRA=0.4%) and LIFT might have the lowest postoperative incontinence in month 1(Wexner) (SUCRA=16.2%). CONCLUSION: Fistulectomy might have the lowest complication rate, which might be the relatively superior surgical technique for treating CAF.

Comparison of clinical outcomes of anal fistula plug and endoanal advancement flap repair treating the complex anal fistula: a systematic review and meta-analysis.

Anal fistula (AF) is a common disease with high prevalence and surgical operations are effective treatments in clinical work. There exist many well-known surgical techniques treating complex anal fistula (CAF), however, none is ideal. To compare the superiority of Anal fistula plug (AFP) and Endoanal advancement flap repair (EAFR) for complex anal fistula. We searched worldwide databases including Pubmed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and SinoMed from their inception to March 2023. Studies comparing the outcomes of AFP and EAFR were included according to the PICO principles. The indicators of the healing rate, recurrence rate, wound infection rate, and complication rate, et al. were extracted and compared between different surgical methods. 5 RCTS and 7 non-RCTs were included in the meta-analysis with a total of 847 patients (341 patients conducted with AFP and 506 patients with EAFR). By combining the total effect of the 12 articles, we found that there was a statistical difference reporting the healing rate of AFP 48.3% and EAFR 64.4% treating the CAF (OR 0.68, 95% CI 0.30,1.55, P = 0.03), and EAFR has a better healing rate. However, there was no significant difference in terms of the recurrence rate (OR 1.68, 95% CI 0.80,3.54, P = 0.17), the wound infection rate (OR 1.82, 95% CI 0.95,3.52, P = 0.07), and the complication rate (OR 1.06, 95% CI 0.70,1.61, P = 0.77) either in the 12 articles or in the subgroup. The meta-analysis indicated that the EAFR was superior to AFP in terms of the healing rate treating the CAF, however, there were no significant differences between the two groups when it came to the recurrence rate, the wound infection rate, and the complication rate. EAFR might be one initial treatment for the complex cryptoglandular anal fistulas compared with AFP.

The efficacy and safety of Chinese herbal medicine for reducing wound complications after anal fistula surgery: A protocol for systematic review and meta-analysis.

BACKGROUND: Anal fistula is one of the most common diseases in anorectal surgery. The wound healing after surgery can affect the prognosis of patients. We conducted a protocol for systematic review and meta-analysis to assess the efficacy and safety of Chinese herbal medicine for reducing wound complications after anal fistula surgery. METHODS: We have prepared this protocol in accordance with the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA-P) statement. We will search the following databases: the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, Chinese Biomedical Literature Database, Pubmed, Embase, Web of Science, and the Cochrane library. Two authors will independently assess the risk of bias of the included studies based on the bias risk assessment tool recommended in the Cochrane "Risk of bias" assessment tool. All calculations are carried out with STATA13.0 software. RESULTS: A synthesis of current evidence of Chinese herbal medicine for wound management after anal fistula surgery will be shown in this protocol. CONCLUSION: This study may provide more convincing evidence to help clinicians make decisions when dealing with anal fistula patients after surgery.

Perineal burn injury with hidradenitis suppurativa: A case report.

RATIONALE: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease which usually presents with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas. Severe HS has interconnecting sinus tracts and when it occurs in the perianal region, perianal fistulas can form. Obesity and smoking are 2 risk factors for the development of HS. PATIENT CONCERNS: We report a case of a 33-year-old male diagnosed with perianal HS and perianal fistula following a burn injury to the area that occurred during childhood. DIAGNOSIS: Through integration of the clinical signs and imaging results, the patient was diagnosed with HS, Hurley stage III with perianal fistulas. INTERVENTIONS: The patient accepted surgical therapy. Performed under the general anesthesia, the procedure comprised sinus tracts excision and drainage. OUTCOMES: The patient was discharged from the hospital 6 weeks after surgery. LESSONS: The pathogenesis of the HS in this case was the burn injury interfering with sweat gland formation around the anus. Moreover, the scar from the burn made surgical treatment difficult.

Flexible Asymmetrical Solid-State Supercapacitors Based on Laboratory Filter Paper.

In this study, a flexible asymmetrical all-solid-state supercapacitor with high electrochemical performance was fabricated with Ni/MnO2-filter paper (FP) as the positive electrode and Ni/active carbon (AC)-filter paper as negative electrode, separated with poly(vinyl alcohol) (PVA)-Na2SO4 electrolyte. A simple procedure, such as electroless plating, was introduced to prepare the Ni/MnO2-FP electrode on the conventional laboratory FP, combined with the subsequent step of electrodeposition. Electrochemical results show that the as-prepared electrodes display outstanding areal specific capacitance (1900 mF/cm(2) at 5 mV/s) and excellent cycling performance (85.1% retention after 1000 cycles at 20 mA/cm(2)). Such a flexible supercapacitor assembled asymmetrically in the solid state exhibits a large volume energy density (0.78 mWh/cm(3)) and superior flexibility under different bending conditions. It has been demonstrated that the supercapacitors could be used as a power source to drive a 3 V light-emitting diode indicator. This study may provide an available method for designing and fabricating flexible supercapacitors with high performance in the application of wearable and portable electronics based on easily available materials.

Preparation of pH-Sensitive Dextran Nanoparticle for Doxorubicin Delivery.

One of challenge for cancer therapy is efficient delivery of anticancer agents into tumor sites to increase efficiency of drugs and reduce side effects. To overcome this challenge, we designed pH- sensitive doxorubicin prodrug (DEX-PEI-DOX) nanoparticles based on dextran-poly(ethylene imine) copolymers (DEX-PEI). The DEX-PEI-DOX conjugates were conveniently prepared by grafting PEI to dextran, and then anticancer drug doxorubicin (DOX) were conjugated to DEX-PEI through acid cleavable cis-aconityl bonds. The experiments of dynamic light scattering (DLS) and transmission electron microscopy (TEM) represented that size of dextran nanoparticles was about 120 nm with uniform spherical shape. In vitro drug release from self-assembled nanoparticles was dependent on the pH of medium due to the cis-aconityl linkage. Confocal images revealed that dextran based pH-sensitive DOX delivery nanoparticle could enter into Human breast carcinoma (MCF-7) cells easily. Therapeutic efficacy against MCF-7 cells in vitro was evaluated through MTT assays and the results showed that dextran nanoparticle had obvious anticancer ability. All above results indicated this pH-sensitive DOX-loaded nanoparticles system would be a useful candidate for cancer therapy.

Pattern formation of coupled spiral waves in bilayer systems: rich dynamics and high-frequency dominance.

The interaction of two spiral waves with independent frequencies in a bilayer oscillatory medium (one spiral in each layer) and with a symmetric coupling e is studied. If the spirals have different frequencies, the faster spiral is unaffected by the slower one, and the slower can show a variety of behaviors, which depend on e and include, in order of increasing e, phase drifting, amplitude modulation, amplitude domination, and phase synchronization. This high-frequency dominance, the asymmetric driving-response effect under the condition of a symmetric coupling, is generic and independent of whether the coupled spiral waves are outwardly rotating or inwardly rotating spirals. If the spirals have identical frequencies, they may even show complete synchronization, parallel drift, or circular drift, depending on the relative rotation direction of the two spirals and their initial separation distance. Comparisons with coupled spirals in monolayer media, previous works on coupled spirals in bilayer systems, and coupled phase oscillators are made.

Projective synchronization of two coupled excitable spiral waves.

Interaction of two identical excitable spiral waves in a bilayer system is studied. We find that the two spiral waves can be completely synchronized if the coupling strength is sufficiently large. Prior to the complete synchronization, we find a new type of weak synchronization between the two coupled systems, i.e., the spiral wave of the driven system has the same geometric shape as the spiral wave of the driving system but with a much lower amplitude. This general behavior, called projective synchronization of two spiral waves, is similar to projective synchronization of two coupled nonlinear oscillators, which has been extensively studied before. The underlying mechanism is uncovered by the study of pulse collision in one-dimensional systems.

Novel type of amplitude spiral wave in a two-layer system.

Interaction of spiral waves in a two-layer system described by a model of coupled complex Ginzburg-Landau equations with negative-feedback couplings ε(1) and ε(2) is studied. Synchronization of two spiral waves can be broadly found if ε(1)+ε(2) is sufficiently large. Prior to the synchronization, under the condition of strongly asymmetric coupling (∣ε(1)-ε(2)∣≫0), a novel type of spiral wave, amplitude spiral wave, exists in the driven system. The pattern of amplitude spiral wave shows the spiral in the amplitude and without a singularity point (tip), compared to usual spiral waves known for phase with amplitude uniform far away from tips and rotating around tips.

Transition zone in controlling spatiotemporal chaos.

The controllability of spatiotemporal chaos is investigated. Contrary to our common sense that there is only one transition point (i.e., a critical control strength) for successful control, we find that actually a transition zone exists, connecting two transition points for the local and global stabilities of the controlled state, respectively. Within the zone, the controllable probability increases from zero to one for random initial conditions. This behavior is found to be very generic and is expected to have a severe consequence in realistic applications in the control of spatiotemporal chaos.

Chaos synchronization in coupled systems by applying pinning control.

Chaos synchronization in coupled chaotic oscillator systems with diffusive and gradient couplings forced by only one local feedback injection signal (boundary pinning control) is studied. By using eigenvalue analysis, we obtain controllable regions directly in control parameter space for different types of coupling links (including diagonal coupling and nondiagonal couplings). The effects of both diffusive and gradient couplings on chaos synchronization become clear. Some relevant factors on control efficiency such as coupled system size, transient process, and feedback signal intensity are also studied.

Chirality effect on the global structure of spiral-domain patterns in the two-dimensional complex Ginzburg-Landau equation.

It is well known that in the single-spiral-stable parameter regimes of the two-dimensional complex Ginzburg-Landau equation, spiral-domain patterns spontaneously appear. These patterns are disordered cells of frozen spiral waves well separated by thin walls (shocks), and to a good approximation, the walls are segments of hyperbolas. In this paper, we take a closer look at the global structure of spiral-domain patterns by using rigorous mathematical analysis and considering the unusual effect of the chirality (handedness) of spiral wave. An equation that determines the slope of the shock line is derived. We generalize this analytical method to study the interaction of a pair of spirals with different rotation frequencies, and obtain the geometrical structures of the shock line and the wave front of the invasion wave in transient processing.