Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level.

Introduction: Previous studies indicated that Wuda Granule (WDG) has been applied in the treatment of gastrointestinal motility disorder (GMD), but the effect and underlying mechanisms is yet to be elucidated. This study aimed to explore the mechanism and pharmacological effect of WDG for GMD via network analysis, verification of animal experiments and clinical experiments. Methods: The chemical components of WDG were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP, http://lsp.nwu.edu.cn/index.php), and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/Index/) according to oral bioavailability (OB) ≥ 20% and drug-likeness (DL) ≥ 0.10. The targets of WDG compounds were retrieved from the Swiss Target Prediction database (http://www.swisstargetprediction.ch/) and targets related to GMD were retrieved from GeneCards database (https://www.genecards.org/). Network analysis were performed to screen the key active compounds of WDG and its hub targets. Then the pharmacological effect of WDG were verified via vivo experiments in rats and clinical experiments. Results: The results showed that 117 effective active compounds of WDG were screened and 494 targets of WDG compounds targeting GMD were selected. These targets were involved in the biological process of inflammatory regulation and the regulation of gastrointestinal motility. The mechanism was mainly involved in the regulation of PI3K-Akt signaling pathway and Rap1 signaling pathway. In addition, molecular docking analysis suggested that eight key active compounds of WDG may be mainly responsible for the effect of WDG on GMD by targeting HARS, AKT, and PIK3CA, respectively. Animal experiments and clinical trials both suggested that WDG could exert therapeutical effect on GMD via inhibiting inflammation and promoting gastrointestinal motility, it could also improve digestive function of patients with laparoscopic colorectal cancer after surgery. Conclusion: This study was the first to demonstrate that WDG improved GMD mainly via inhibiting inflammatory level and promoting gastrointestinal motility, providing new insights for the understanding of WDG for GMD, inspiration for future research and reference for clinical strategy in terms of the treatment of GMD.

A Novel Molecular Reservoir Based on Reverse Self-Assembled Liquid Crystals - A New Strategy for Prolonging the Duration in Action of Analgesics.

PURPOSE: The aim of this study was to develop liquid crystal (LC) precursors to obtain novel long-acting analgesics for injection based on depot systems and compare the difference between the cubic and hexagonal precursors in delivering Diclofenac sodium (DS). METHODS: Diclofenac sodium liquid crystal precursor injections were prepared and characterized, followed by in vitro release, pharmacodynamic, and pharmacokinetic studies. RESULTS: The optimal formulations were prepared with a ratio of Phytantriol/ethanol/water as 76:19:5 for cubic LC precursors, and a ratio of Phytantriol/ethanol/water/Vitamine-E acetate as 72:18:5:5 for hexagonal, both loading various drug dosages (2.5%, 3.75% and 5%), respectively. Polarized light microscopy and small angle diffraction confirmed that the precursors were isotropic fluids and transformed into gels with Pn3m or HII framework in water. Rheological studies have shown that precursors belong to Newtonian fluids and gels to pseudoplastic fluids. The release showed that the DS in the commercial injection (DS-inj) was completely liberated within 6 h, whereas only 46.55% and 49.73% of the DS in 2.5% cubic precursors and 2.5% hexagonal precursors were freed, respectively. Pharmacodynamic studies have shown that cubic, hexagonal and DS-inj raised the pain threshold in mice by 169.4%, 157.3% and 113.79%, respectively. The mean retention times of DS in cubic and hexagonal were 3.16 and 2.67 times longer than DS-inj, respectively, according to pharmacokinetic results. CONCLUSION: In conclusion, cubic and hexagonal are both promising analgesic sustained release formulations. In addition, based only on the current comparison, cubic seems to have a better long-acting effect.

Transdermal administration of ibuprofen-loaded hexagonal liquid crystal gel for enhancement of drug concentration in the uterus: in vitro and in vivo evaluation.

Primary dysmenorrhea is a common disease in women, and oral administration of Ibuprofen (IBU) is associated with first-pass effects and gastrointestinal irritation. Here, we developed ibuprofen-loaded hexagonal liquid crystal (IBU HLC) gel for transdermal administration. In this study, the structure of prepared IBU HLC was characterized using polarizing microscopey (PLM) and small angle X ray diffraction (SAXS). In vitro drug release behavior and percutaneous penetration were investigated, and drug transdermal behavior was observed by confocal laser scanning microscope (CLSM). Finally, the pharmacokinetic profile and tissue distribution were investigated after transdermal administration. The PLM and SAXS results showed that the inner structure of IBU HLC was hexagonal phase. Moreover, in vitro release, skin permeation and CLSM demonstrated that IBU HLC had an excellent sustained-release effect, and a good transdermal penetration effect accompanied by the combination of multiple percutaneous routes. Pharmacokinetic studies indicated that IBU entered the blood circulation through abdominal transdermal administration in small amounts, mainly entering the uterus, and had a certain targeting ability. In conclusion, the IBU HLC gel would be a promising sustained-release preparation for transdermal administration to relieve dysmenorrhea with a significant drug concentration in the uterus.

Transoral Endoscopic Thyroidectomy by Vestibular Approach for Papillary Thyroid Carcinoma with Tumor Size ≥2 cm.

Background: The transoral endoscopic thyroidectomy by vestibular approach (TOETVA) has been developed for papillary thyroid carcinoma (PTC) treatment with satisfactory results. However, there were few malignant thyroid nodules ≥2 cm in previous studies of TOETVA. Therefore, we conducted this study to evaluate the results of treatment by TOETVA for PTC with tumor size ≥2 cm. Materials and Methods: The clinical characteristics and surgical outcomes of 10 PTC patients with tumor size ≥2 cm who underwent TOETVA in our center from June 2018 to August 2021 were, respectively, reviewed. Results: All 10 included PTC patients successfully underwent TOETVA and the mean tumor size was 2.5 ± 0.5 cm. The mean number lymph nodes dissected was 9.6 ± 2.9, and 3.1 ± 3.3 positive lymph nodes were discovered. Postoperatively, transient hypoparathyroidism was recorded in 2 patients (20%), transient recurrent laryngeal nerve injury was noted in 1 patient (10%), transient superior laryngeal nerve injury was noted in 1 patient (10%), and numb chin was identified in 1 patient (10%). The postoperative complications aforementioned recovered within 6 months. During a median follow-up of 23.8 ± 13.1 months, no other complications or tumor recurrence were found. Conclusions: TOETVA is feasible for PTC patients with tumor size ≥2 cm and satisfactory short-term surgical outcomes have achieved in this study. We suggested that experienced surgeons can gradually expand the indications for TOETVA.

A novel hybrid approach for "Scarless" (at the neck) lateral neck dissection for papillary thyroid carcinoma: A case series and literature review.

Lateral neck dissection (LND) is a necessary treatment for thyroid cancer with lateral lymph node metastasis. However, the defect created during open surgery leaves a visible scar on the neck. With advancements in surgical technology, many robotic and endoscopic surgical techniques have been reported as alternatives to open surgery. In this study, we present a case series demonstrating the successful application of a novel hybrid approach for endoscopic LND and a review of different surgical approaches for "scarless" (at the neck) LND. We performed endoscopic LND via a combined chest and transoral approach in 24 patients between January 2021 and March 2022. The surgery was completed successfully in all patients with an average operation time of 298.1 ± 72.9 min. The numbers of positive/retrieved lymph nodes at levels II, III-IV, and VI were 0.7 ± 0.9/8.4 ± 4.1, 3.6 ± 2.7/19.5 ± 6.8, and 4.9 ± 3.9/10.3 ± 4.5, respectively. Complications included transient hypoparathyroidism in 10 patients, transient recurrent laryngeal nerve injury in 1 patient, internal jugular vein (IJN) injury in 1 patient, IJN sacrifice due to cancer invasion in 1 patient, and chyle leak in 1 patient, and no cases of tumor recurrence were observed during follow-up. The present case series indicates that the combined chest and transoral approach is feasible and effective for performing LND. Our review of different approaches for "scarless" (at the neck) LND identified advantages and disadvantages for all techniques. Our novel approach has unique advantages, and thus, it can provide an ideal surgical procedure for specific papillary thyroid carcinoma patients.

Liposome and microemulsion loaded with ibuprofen: from preparation to mechanism of drug transport.

To compare the difference between liposome (LP) and microemulsion (ME) in delivering ibuprofen (IBU) transdermally and explore relative mechanism. IBU-LP and IBU-ME were prepared by ethanol injection and spontaneous emulsification, respectively. The percutaneous delivery was evaluated using Franz diffusion cells. Fourier transform infra-red spectroscopy (FTIR), differential scanning calorimetry (DSC), activation energy (Ea), and confocal laser scanning microscopy (CLSM) were used to investigate the transdermal mechanism. The particle size and encapsulation efficiency were 228.00 ± 8.60 nm, 86.68 ± 1.43%(w/w) for IBU-LP, and 56.74 ± 7.11 nm, 91.08 ± 3.27%(w/w) for IBU-ME. Percutaneous study showed that formulations enhanced permeation and drug retention in the skin. FTIR and DSC showed that the permeation occurred due to the interaction of the formulations with the lipid bilayer and the protein. The decrease in Ea (1.506 and 0.939 kcal/mol) revealed that the stratum corneum (SC) lipid bilayers were significantly disrupted and this destructive effect of IBU-LP was stronger. IBU-LP was superior to IBU-ME in the aspects of transdermal delivery of IBU.

Hexagonal liquid crystalline system containing cinnamaldehyde for enhancement of skin permeation of sinomenine hydrochloride.

Sinomenine hydrochloride (SH) is usually applied to treat rheumatoid arthritis (RA) with severe side effects due to oral administration. Cinnamaldehyde (CA) as essential oil possesses an anti-RA effect and can facilitate transdermal penetration. Hence, this study developed hexagonal liquid crystalline (HII) gels to deliver two components (SH and CA) across the skins. HII gels were prepared and characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and rheology. Moreover, in vitro drug release behavior and ex vivo skin permeation were investigated. Finally, Fourier transforms infrared spectral analysis (FTIR) and confocal laser scanning microscopy (CLSM) were used to explore the skin penetration mechanism. PLM and SAXS showed that the inner structure of the gels was HII phase. The addition of lipophilic or hydrophilic molecules slowed down one another's release and the release model was dominated by Fickian diffusion (n < 0.43). Furthermore, in vitro permeation studies indicated that appropriate CA could improve the skin permeability of SH. FTIR and CLSM suggested that infiltration occurred due to disruption of the lipid bilayer structure and increased fluidity of the skin. In conclusion, HII gels and CA exhibited a penetration-promoting effect for transdermal applications in SH.

In vitro and in vivo evaluation of cinnamaldehyde Microemulsion-Mucus interaction.

The current investigation explores the possible mechanism of the microemulsion drug delivery system to improve the oral bioavailability of cinnamaldehyde (CA), an important food spice, from the perspective of the microemulsion-mucus system. The cinnamaldehyde microemulsion (CA-ME) was prepared by the water titration method combined with the pseudo-ternary phase diagram. The dynamic analysis was applied to detect the drug release in vitro. An intestinal mucosal injury test was conducted to evaluate the safety of CA-ME and drug absorption across the intestinal tract of rats was investigated through an Ussing chamber system. The rheology of blank mucus and drug-loaded mucus was investigated using a rheometer. The bioavailability of CA-ME in rats was evaluated through pharmacokinetic characteristics. The ratio of optimal prescription was Tween 80: 1,2-propanediol: vitamin E oil: CA: water = 24.3:4.8:5:7.5:58.4. The droplets were uniform in size and evenly dispersed. Rheological studies showed that the microemulsion-mucus system all exhibit pseudoplastic fluid behavior, and CA-ME increased the viscosity of the mucus to a certain extent. Compared with CA solution, CA-ME promoted the absorption of CA in various intestinal segments, especially the ileum. Pharmacokinetic experiments showed that the relative bioavailability of CA-ME was enhanced 2.5-fold higher than that of CA solution. ME as a carrier for lipophobic substances, may increase the viscosity of the intestine mucus system to obtain longer residue time and better absorption. PRACTICAL APPLICATIONS: In this study, in vitro absorption Ussing model was combined with rheological and pharmacokinetic analysis to systematically analyze the intestinal mucus mechanism of microemulsion to improve the oral bioavailability of cinnamic aldehyde. It laid the foundation for exploring the absorption and transport of drugs in the intestinal mucus barrier.

Safety and feasibility of the transoral endoscopic thyroidectomy vestibular approach with neuroprotection techniques for papillary thyroid carcinoma.

BACKGROUND: This study aimed to evaluate the feasibility and safety of the trans-oral endoscopic thyroidectomy vestibular approach (TOETVA) with neuroprotection techniques for the surgical management of papillary thyroid carcinoma (PTC). METHODS: Patients with PTC who underwent TOETVA between December 2016 and July 2020 were included in this study, and their relevant clinical characteristics, operational details, and surgical outcomes were reviewed and extracted from their medical records for further analysis. RESULTS: A total of 75 patients successfully underwent TOETVA with zero conversions. Unilateral lobectomy with isthmectomy and total thyroidectomy were completed for 58 and 17 patients, respectively, all using our unique neuroprotective procedure and ipsilateral central neck dissection (CND). The mean number of retrieved lymph nodes versus positive lymph nodes was 6.8 ± 3.7 vs. 1.5 ± 2.3. Postoperative complications included three cases of transient superior laryngeal nerve (SLN) palsy (4.0%), five cases of transient recurrent laryngeal nerve (RLN) palsy (6.7%), 14 cases of transient hypoparathyroidism (18.7%), two cases of numb chin (2.7%) and two cases of flap perforation (2.7%). The follow-up period for patients with PTC lasted for 15.6 ± 10.9 months, during which no other complications or tumor recurrence were observed. CONCLUSION: TOETVA can be safely performed for patients with PTC with satisfactory results during the short-term follow-up period. Our neuroprotection techniques can be integrated into TOETVA, which is worth recommending for PTC patients who desire better cosmetic surgical outcomes.

Endoscopic thyroidectomy via the combined trans-oral and chest approach for cT1-2N1bM0 papillary thyroid carcinoma.

BACKGROUND: Recent years there have been witnessed considerable advances in endoscopic selective lateral neck dissection (LND). However, dissection of lymph nodes at level IV and level VI via the chest approach is inherently challenging. In this study, we used combined trans-oral and chest approach for endoscopic thyroidectomy in patients with cT1-2N1bM0 papillary thyroid carcinoma (PTC). METHODS: Clinical characteristics and surgical outcomes of ten patients with cT1-2N1bM0 PTC who underwent endoscopic thyroidectomy via combination of trans-oral and chest approach between September 2020 and September 2021 were retrospectively reviewed. RESULTS: All 10 patients successfully underwent total thyroidectomy and selective LND via chest approach, while central neck dissection (CND) and supplementary dissection of lymph nodes at level IV were performed via the trans-oral approach. The mean number of positive/retrieved level II, III-IV, and VI lymph nodes were 0.6 ± 1.0/9.8 ± 5.0, 4.6 ± 2.8/23.1 ± 4.7, and 4.9 ± 3.4/10.3 ± 4.6, respectively. Four patients developed transient hypoparathyroidism which spontaneously resolved within 1 month. Five patients developed numbness of lateral neck and ear and one patient experienced limb lift restriction. No other complications or tumor recurrence occurred during follow-up. CONCLUSION: It is feasible to perform total thyroidectomy, CND, and selective LND via combined trans-oral and chest approach, and satisfactory short-term outcomes were observed in this cohort. This approach may offer one more option for cT1-2N1bM0 PTC patients, especially those in whom metastatic lymph nodes at level IV or level VI are detected by preoperative examination.

Qin's seven steps for endoscopic selective lateral neck dissection via the chest approach in patients with papillary thyroid cancer: experience of 35 cases.

BACKGROUND: Endoscopic thyroidectomy is widely performed as it does not result in neck scar. However, there is a paucity of reports pertaining to completely endoscopic lateral neck dissection (LND). In this study, we introduce our step-wise approach for performing endoscopic selective LND via the chest-breast approach. We refer to this approach as Qin's seven steps. METHODS: The Qin's seven steps are: (1) establishment of working space range; (2) dissection of lymph nodes between the SCM and the sternohyoid muscle (level IV) and exposure of omohyoid; (3) dissection of lymph nodes at level IV; (4) dissection of lymph nodes at level III; (5) dissection of lymph nodes at carotid triangle (level III); (6) exposure of accessory nerve and dissection of lymph nodes at level II a; (7) dissection of lymph nodes at level II b. We reviewed the clinical data of 35 patients with papillary thyroid cancer (PTC) who were operated using the Qin's seven steps. RESULTS: All 35 patients successfully underwent LND; bilateral LND was performed in 5 patients. The mean tumor size was 1.8 ± 1.0 cm; seven patients had multiple lesions. The mean number of retrieved lymph nodes in level II, III and IV were 8.8 ± 5.6, 6.1 ± 4.0 and 9.3 ± 5.1, respectively. As for complications, there were 3 cases of accessory nerve injury and 1 case of hypoglossal nerve injury. Internal jugular vein injury, cervical plexus injury and lymphatic leakage occurred in 2, 7, and 1 patients, respectively. CONCLUSION: The Qin's seven steps for performing endoscopic selective LND could be safely used in PTC patients with lateral lymph node metastasis. Satisfactory results were achieved in the short-term follow-up period. We recommend the use of Qin's seven steps for PTC patients who are not desirous of neck scar.

In Situ Liquid Crystal Gel as a Promising Strategy for Improving Ocular Administration of Dexamethasone: Preparation, Characterization, and Evaluation.

The purpose of this study was to design an in situ liquid crystal gel (ISLG) as an ophthalmic drug delivery system for dexamethasone (DEX) to enhance its eye retention and ocular bioavailability. The in situ liquid crystal gels (ISLGs) were prepared using a phytantriol/PEG400/water (65:30:5, w/w) ternary system. Polarized light microscope (PLM), small-angle X-ray scattering (SAXS), and rheology analysis confirmed that the internal structure of the preparations was Pn3m cubic phase liquid crystal gels with pseudoplastic fluid properties. Meanwhile, in vitro release behavior of the preparations conforms to the Higuchi equation. Corneal penetration experiments showed that compared with DEX sodium phosphate eye drops, DEX-ISLGs(F2) produced a 5.45-fold increase in the Papp value, indicating a significant enhancement of corneal penetration. In addition, in vivo experiments have confirmed that the ISLGs have better biocompatibility and longer retention time in the cornea. Simultaneously, corneal hydration level, eye irritation experiments, and histological observations proved the safety of the preparations. Pharmacokinetic studies have shown that the ISLG could maintain the DEX concentration in aqueous humor for at least 12 h after administration, which significantly improves the bioavailability of the drug. Collectively, these results indicated that ISLG would be a potential drug carrier for the treatment of diabetic retinopathy (DR).

Physicochemical evaluation and pharmacodynamics of itraconazole-loaded liquid crystal precursor for vaginal delivery.

PURPOSE: To develop a liquid crystal (LC) precursor that can be used as a novel vaginal delivery system for Itraconazole (ITZ) and evaluate its pharmacodynamics. METHODS: The LC precursor was prepared by using phytantriol (PYT) as lipid matrix and N, N-dimethylformamide (DMAC) as solvent. Swelling studies were performed to assess the phase conversion ability. The formulations were characterized by crossed polarized light microscopy (CPLM), small-angle X-ray scattering (SAXS). Moreover, the rheological and in vitro drug release behavior were investigated. Then the vaginal retention time of ITZ in the optimal prescription was evaluated. Finally, the pharmacodynamics studies of the ITZ-loaded LC precursor were performed in a mouse model of vulvovaginal candidiasis (VVC). RESULTS: The LC precursor could transform to LC gels after administration into the vagina. Based on PLM and SAXS, the LC gels, formed after phase-conversion, were cubic LC. The LC precursor was non-Newtonian, while the LC gels exhibited a pseudo-plastic fluid behavior. In vitro release results revealed that F2 (68.0%) had a higher cumulative drug release than that of F1 (59.17%) at 72 h. Most of the LC gels could be retained in the vagina of mice for 24-36 h. Pharmacodynamics studies showed that there was only mild inflammation or no inflammatory stimulation in the control group. The ITZ-loaded LC precursor significantly improved the symptoms of vaginitis in mice and had a better therapeutic effect than that of the positive control group. CONCLUSIONS: The ITZ-loaded LC precursor would be a promising formulation for vaginal drug delivery.

Application of Nano-Carbon in lymph node dissection and protection of parathyroid glands in 3D laparoscopic thyroidectomy / 中国内镜杂志

Objective To explore the clinical significance of Nano-Carbon particles and 3D laparoscopy in central compartment lymph node dissection and parathyroid glands protection in treatment of cN0 thyroid cancer. Methods We conduct a retrospective analysis of sixty-five patients with cN0 thyroid cancer who were received 3D laparoscopic thyroidectomy in the last 3 years. All patients were received total resection of thyroid plus the affected side and (or) contralateral side central compartment lymph node dissection. All patients were allocated to control group (n = 32) and carbon nano-particles trace group (tracer group, n = 33). The lymph node-related indexes (including number of dissected lymph node at Ⅵ area, number of Metastatic lymph node and Frozen lymph node-positive rate at Ⅵ area), serum calcium (24 h after surgery) and PTH (48 h after surgery) were collected and compared between the 2 groups. Results Number of dissected lymph node at Ⅵ area, positive rates of intraoperative frozen-section examination of parathyroid glands and PTH (48 h after surgery) were found statistical higher in nanoparticles group than control (P < 0.05). No statistical difference were found in Number of Metastatic lymph node and serum calcium (24 h after surgery) (P < 0.05). Conclusion The clinical significance of carbon nanoparticles and 3D laparoscopy is effective and feasible for central compartment lymph node dissection and parathyroid glands protection in treatment of cN0 thyroid cancer.

Application of Nano-Carbon in lymph node dissection and protection of parathyroid glands in 3D laparoscopic thyroidectomy / 中国内镜杂志

Objective To explore the clinical significance of Nano-Carbon particles and 3D laparoscopy in central compartment lymph node dissection and parathyroid glands protection in treatment of cN0 thyroid cancer. Methods We conduct a retrospective analysis of sixty-five patients with cN0 thyroid cancer who were received 3D laparoscopic thyroidectomy in the last 3 years. All patients were received total resection of thyroid plus the affected side and (or) contralateral side central compartment lymph node dissection. All patients were allocated to control group (n = 32) and carbon nano-particles trace group (tracer group, n = 33). The lymph node-related indexes (including number of dissected lymph node at Ⅵ area, number of Metastatic lymph node and Frozen lymph node-positive rate at Ⅵ area), serum calcium (24 h after surgery) and PTH (48 h after surgery) were collected and compared between the 2 groups. Results Number of dissected lymph node at Ⅵ area, positive rates of intraoperative frozen-section examination of parathyroid glands and PTH (48 h after surgery) were found statistical higher in nanoparticles group than control (P < 0.05). No statistical difference were found in Number of Metastatic lymph node and serum calcium (24 h after surgery) (P < 0.05). Conclusion The clinical significance of carbon nanoparticles and 3D laparoscopy is effective and feasible for central compartment lymph node dissection and parathyroid glands protection in treatment of cN0 thyroid cancer.