In Situ Gelling Eye Drops of Tacrolimus with Improved Ocular Delivery and Therapeutic Efficacy.

In situ gelling eye drops of tacrolimus (FK506 Gel) were developed to address the formulation challenge of tacrolimus for anterior ocular inflammatory diseases. Both in silico and in vitro investigations were conducted to screen a suitable cyclodextrin species to increase the drug solubility. Guanosine was employed as the gelator and combined with inclusion complexes of tacrolimus in the presence of borate anions to obtain FK506 Gel, which gelated when came into contact with cations in tear fluid and led to the formation of a nanofibrous hydrogel. The versatility of our design to improve the solubility and ocular retention of the hydrophobic drug was demonstrated in vivo with coumarin 6 as a model drug. A mouse dry eye model was used to evaluate the therapeutic effects of FK506 Gel, which, in combination with the biocompatibility study, suggested that FK506 Gel served as a superior treatment for anterior ocular inflammatory diseases.

Low-resistivity Ohmic contacts of Ti/Al on few-layered 1T'-MoTe2/2H-MoTe2 heterojunctions grown by chemical vapor deposition.

This study explores the phase-controlled growth of few-layered 2H-MoTe2, 1T'-MoTe2, and 2H-/1T'-MoTe2 heterostructures and their impacts on metal contact properties. Cold-wall chemical vapor deposition (CW-CVD) with varying growth rates of MoOx and reaction temperatures with Te vapors enabled the growth of continuous thin films of either 1T'-MoTe2 or 2H-MoTe2 phases on two-inch sapphire substrates. This methodology facilitates the meticulous optimization of chemical vapor deposition (CVD) parameters, enabling the realization of phase-controlled growth of few-layered MoTe2 thin films and their subsequent heterostructures. The study further investigates the influence of a 1T'-MoTe2 intermediate layer on the electrical properties of metal contacts on few-layered 2H-MoTe2. Bi-layer Ti/Al contacts directly deposited on 2H-MoTe2 exhibited Schottky behavior, indicating inefficient carrier transport. However, introducing a few-layered 1T'-MoTe2 intermediate layer between the metal and 2H-MoTe2 layers improved the contact characteristics significantly. The resulting Al/Ti/1T'-MoTe2/2H-MoTe2 contact scheme demonstrates Ohmic behavior with a specific contact resistance of around 1.7 × 10-4 Ω cm2. This substantial improvement is attributed to the high carrier concentration of the 1T'-MoTe2 intermediate layer which could be attributed tentatively to the increased tunneling events across the van der Waals gap and enhancing carrier transport between the metal and 2H-MoTe2.

Misdiagnosis of hemangioma of left triangular ligament of the liver as gastric submucosal stromal tumor: Two case reports.

BACKGROUND: Extragastric lesions are typically not misdiagnosed as gastric submucosal tumor (SMT). However, we encountered two rare cases where extrinsic lesions were misdiagnosed as gastric SMTs. CASE SUMMARY: We describe two cases of gastric SMT-like protrusions initially misdiagnosed as gastric SMTs by the abdominal contrast-enhanced computed tomography (CT) and endoscopic ultrasound (EUS). Based on the CT and EUS findings, the patients underwent gastroscopy; however, no tumor was identified after incising the gastric wall. Subsequent surgical exploration revealed no gastric lesions in both patients, but a mass was found in the left triangular ligament of the liver. The patients underwent laparoscopic tumor resection, and the postoperative diagnosis was hepatic hemangiomas. CONCLUSION: During EUS procedures, scanning across different layers and at varying degrees of gastric cavity distension, coupled with meticulous image analysis, has the potential to mitigate the likelihood of such misdiagnoses.

Large-area and few-layered 1T'-MoTe2thin films grown by cold-wall chemical vapor deposition.

This study employs cold-wall chemical vapor deposition to achieve the growth of MoTe2thin films on 4-inch sapphire substrates. A two-step growth process is utilized, incorporating MoO3and Te powder sources under low-pressure conditions to synthesize MoTe2. The resultant MoTe2thin films exhibit a dominant 1T' phase, as evidenced by a prominent Raman peak at 161 cm-1. This preferential 1T' phase formation is attributed to controlled manipulation of the second-step growth temperature, essentially the reaction stage between Te vapor and the pre-deposited MoOxlayer. Under these optimized growth conditions, the thickness of the continuous 1T'-MoTe2films can be precisely tailored within the range of 3.5-5.7 nm (equivalent to 5-8 layers), as determined by atomic force microscopy depth profiling. Hall-effect measurements unveil a typical hole concentration and mobility of 0.2 cm2Vs-1and 7.9 × 1021cm-3, respectively, for the synthesized few-layered 1T'-MoTe2films. Furthermore, Ti/Al bilayer metal contacts deposited on the few-layered 1T'-MoTe2films exhibit low specific contact resistances of approximately 1.0 × 10-4Ω cm2estimated by the transfer length model. This finding suggests a viable approach for achieving low ohmic contact resistance using the 1T'-MoTe2intermediate layer between metallic electrodes and two-dimensional semiconductors.

Endoscopic ultrasound-guided lauromacrogol injection for treatment of colorectal cavernous hemangioma: Two case reports.

BACKGROUND: Colorectal cavernous hemangioma is a rare vascular malformation resulting in recurrent lower gastrointestinal hemorrhage, and can be misinterpreted as colitis. Surgical resection is currently the mainstay of treatment, with an emphasis on sphincter preservation. CASE SUMMARY: We present details of two young patients with a history of persistent hematochezia diagnosed with colorectal cavernous hemangioma by endoscopic ultrasound (EUS). Cavernous hemangioma was relieved by several EUS-guided lauromacrogol injections and the patients achieved favorable clinical prognosis. CONCLUSION: Multiple sequential EUS-guided injections of lauromacrogol is a safe, effective, cost-efficient, and minimally invasive alternative for colorectal cavernous hemangioma.

2023: A year of accomplishments for the 13 Science Citation Index Expanded- and Emerging Sources Citation Index-indexed Baishideng journals.

In 2023, Baishideng Publishing Group (Baishideng) routinely published 47 open-access journals, including 46 English-language journals and 1 Chinese-language journal. Our successes were accomplished through the collective dedicated efforts of Baishideng staffs, Editorial Board Members, and Peer Reviewers. Among these 47 Baishideng journals, 7 are included in the Science Citation Index Expanded (SCIE) and 6 in the Emerging Sources Citation Index (ESCI). With the support of Baishideng authors, company staffs, Editorial Board Members, and Peer Reviewers, the publication work of 2023 is about to be successfully completed. This editorial summarizes the 2023 activities and accomplishments of the 13 SCIE- and ESCI-indexed Baishideng journals, outlines the Baishideng publishing policy changes and additions made this year, and highlights the unique advantages of Baishideng journals.

Characteristics and Risk Factors of Functional Dyspepsia Fulfilling the Rome IV Criteria Overlapping With Gastroesophageal Reflux Disease, Irritable Bowel Syndrome, and Functional Constipation in South China.

Background/Aims: Functional dyspepsia (FD) overlapping with other gastrointestinal disorders are quite common. The characteristics of FD overlap in Chinese population with latest Rome IV criteria were unclear. This large-scale outpatient-based study assessed the characteristics of FD overlap in South China. Methods: Consecutive FD patients visited the Gastroenterology Clinic at 2 tertiary medical centers in Hangzhou, China who fulfilled the Rome IV criteria were enrolled. Complete questionnaires related to the gastrointestinal symptoms (Rome IV criteria), Reflux Disease Questionnaire, anxiety and depression, quality of sleep and life, and demographic information were collected. Results: Among the total of 3281 FD patients, 50.69% overlapped with gastroesophageal reflux disease, 21.46% overlapped with irritable bowel syndrome, 6.03% overlapped with functional constipation. FD overlap had higher proportion of single/divorced/widowed rate, high education level, being employed, drinking, night shift, unhealthy dietary habit than FD only (P < 0.05). They had higher frequency of consultation and economic burden, as well as lower scores in quality of life (P < 0.001). Multivariate logistic regression showed that increasing age, female, low body mass index, history of gastroenteritis, anxiety, depression, and poor sleep quality were independent risk factors for FD overlap. Conclusions: FD overlap was quite common in China with high economic burden and poor quality of life, FD patients with history of gastroenteritis, anxiety, depression, and poor sleep quality were more likely to have overlap disorders. Awareness of the physical and psychosocial stressors in overlapping condition would help optimize the management of FD overlap in clinical practice.

Influence of Age and Gender on Nasal Airway Patency as Measured by Active Anterior Rhinomanometry and Acoustic Rhinometry.

In this study, we aimed to investigate the influences of age and gender on nasal airway patency, as measured by both active anterior rhinomanometry (AAR) and acoustic rhinometry (AR). The nasal airway patency of healthy subjects was evaluated using AAR and AR. In AAR, the subjects generated airflow actively through inspiration and expiration in repetitions of 10, while nasal patency was measured at an inspiratory and expiratory reference pressure of 75 Pa. In AR, we assessed the geometry of the nasal cavity through the analysis of sound waves reflected from the nasal cavities in order to measure both cross-sectional areas and nasal volumes. The subjects were divided by gender, with all males and females then grouped by ages of 20-39 years, 40-59 years and ≥60 years. There were 40 subjects in each group. The mean resistance measured by AAR and the cross-sectional areas and nasal volumes measured by AR were not different between the different age groups; however, the cross-sectional areas and nasal volumes were found to be lesser in females than in males. Our results showed that nasal airway patency was not affected by age, while females were shown to have wider nasal passages than males.

Improving ocular bioavailability of hydrophilic drugs through dynamic covalent complexation.

The clinical benefits of diquafosol tetrasodium (DQS), a hydrophilic P2Y2 receptor agonist for dry eye, have been hindered by a demanding dosing regimen. Nevertheless, it is challenging to achieve sustained release of DQS with conventional drug delivery vehicles which are mainly designed for hydrophobic small molecule drugs. To address this, we developed an affinity hydrogel for DQS by taking advantage of borate-mediated dynamic covalent complexation between DQS and hydroxypropyl guar. The resultant formulation (3% DQS Gel) was characterized by sustained release, low corneal permeation, and extended ocular retention, which were desirable attributes for ocular surface drug delivery. Both in vitro and in vivo studies had been carried out to verify the biocompatibility of 3% DQS Gel. Using corneal fluorescein staining, the Schirmer's test, PAS staining, quantitative PCR and immunohistological analyses as outcome measures, the superior therapeutic effects of 3% DQS Gel over PBS, the hydrogel vehicle and free DQS were demonstrated in a mouse dry eye model. Our DQS delivery strategy reported herein is readily applicable to other hydrophilic small molecule drugs with cis-diol moieties, thus providing a general solution to improve clinical outcomes of numerous diseases.

Validation of the clinical applicability of the brief self-administered waterless empirical taste test during the era of COVID-19.

BACKGROUND: This study was performed to test the clinical applicability of a new taste test, the Brief Self-Administered Waterless Empirical Taste Test (B-WETT) in the era of COVID-19. METHODS: Sixty healthy volunteers and 60 patients experiencing gustatory dysfunction were enrolled. All subjects received both the Self-Administered WETT and the new B-WETT which are comprised of disposable plastic strips containing sucrose, citric acid, sodium chloride, caffeine, and monosodium glutamate tastants to evaluate taste function. The healthy volunteers were re-tested with the WETT and B-WETT after an inter-test interval of at least 7 days to measure retest reliability. RESULTS: The sum scores of five tastants of the first test were 25.7 for males and 29.5 for females in WETT, and 12.4 for males and 15.2 for females in B-WETT. There were significant differences in the sum scores between males and females whether in WETT or B-WETT. The sum scores strongly correlated between WETT and B-WETT, whether in healthy volunteers or in patients with gustatory dysfunction (r >0.7). There was also a strong correlation between the first and second tests of B-WETT for the sum scores. CONCLUSION: This study shows that B-WETT is a valid and reliable taste test, and is convenient for use in the era of COVID-19 to evaluate the taste function of patients.

The analgesic effects of ß-elemene in rats with neuropathic pain by inhibition of spinal astrocytic ERK activation.

Neuropathic pain takes a heavy toll on individual well-being, while current therapy is far from desirable. Herein, we assessed the analgesic effect of ß-elemene, a chief component in the traditional Chinese medicine Curcuma wenyujin, and explored the underlying mechanisms at the level of spinal dorsal horn (SDH) under neuropathic pain. A spared nerve injury (SNI)-induced neuropathic pain model was established in rats. Intraperitoneal injection (i.p.) of ß-elemene was administered for 21 consecutive days. Mechanical allodynia was explored by von Frey filaments. The activation of the mitogen-activated protein kinase (MAPK) family (including ERK, p38, and JNK) in spinal neurons, astrocytes, and microglia was evaluated using immunostaining 29 days after SNI surgery. The expression of GFAP, Iba-1, p-ERK, p-JNK, and p-p38 within the SDH was measured using immunoblotting. The levels of proinflammatory cytokines (including TNF-α, IL-1ß, and IL-6) were measured with ELISA. The levels of oxidative stress indicators (including MDA, SOD, and GSH-PX) were detected using biochemical tests. Consecutive i.p. administration of ß-elemene relieved SNI-induced mechanical allodynia (with an EC50 of 16.40 mg/kg). SNI significantly increased the expression of p-ERK in spinal astrocytes but not microglia on day 29. ß-elemene reversed spinal astrocytic ERK activation and subsequent upregulation of proinflammatory cytokines in SNI rats, with no effect on the expression of p38 and JNK in spinal glia. ß-elemene also exerted antioxidative effects by increasing the levels of SOD and GSH-PX and decreasing the level of MDA. Our results suggest that SNI induces robust astrocytic ERK activation within the SDH in the late phase of neuropathic pain. ß-elemene exerts remarkable analgesic effects on neuropathic pain, possibly by inhibiting spinal astrocytic ERK activation and subsequent neuroinflammatory processes. Our findings suggest that ß-elemene might be a promising analgesic for the treatment of chronic pain.

Thyroid Disorders and Dementia Risk: A Nationwide Population-Based Case-Control Study.

BACKGROUND AND OBJECTIVES: Dementia has been gaining attention in aging societies and is estimated to affect 50 million adults globally in 2020, and 12% of the US population may develop a thyroid disorder in their lifetime. There have been limited studies investigating the correlation between thyroid disorder and dementia in the Asian population. METHODS: Our large nationwide population-based case-control study used the Taiwanese National Health Insurance Research Database. A total of 7,843 adults with newly diagnosed dementia without a history of dementia or neurodegenerative disease between 2006 and 2013 were identified and included in our study. In addition, 7,843 adults without dementia diagnosis before the index date were age and sex-matched as controls. Diagnosis of hyperthyroidism or hypothyroidism before the diagnosis of dementia or the same index date was identified. Results were obtained from logistic regression models and adjusted for sex, age, history of hypertension, diabetes, coronary artery disease, depression, hyperlipidemia, alcohol dependence syndrome, tinnitus, hearing loss, and radioactive iodine treatment. RESULTS: A total of 15,686 patients were included in the study. Both case and control groups were slightly predominantly female (4,066 [51.8%]). The mean (SD) age for those with dementia was 74.9 (11.3) years and for those without dementia was 74.5 (11.3) years. Among patients aged 65 years or older, a history of hypothyroidism was associated with an increased risk of being diagnosed with dementia (adjusted odds ratio [aOR] 1.81; 95% CI 1.14-2.87; p = 0.011), which was an association not present in patients older than 50 years but younger than 65 years. We found that this association was most significant among patients aged 65 years or older with a history of hypothyroidism who received hypothyroidism medication (aOR 3.17; 95% CI 1.04-9.69; p = 0.043). DISCUSSION: Our large-scale case-control study found that among people aged 65 years or older, those with a history of hypothyroidism were associated with an 81% increased risk of having dementia and among those, there was a more than 3-fold increased dementia risk with thyroid conditions that required thyroid hormone replacement treatment. Future well-controlled prospective longitudinal studies should be conducted to elucidate these potential mechanisms and relationships. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that among patients aged 65 years or older, a history of hypothyroidism was associated with an increased risk of being diagnosed with dementia.

Transoral Robotic Surgery for Early-T Stage Glottic Cancer Involving the Anterior Commissure-News and Update.

BACKGROUND: About 20% of all glottic carcinomas involve the anterior commissure (AC), and AC involvement was deemed to be a risk factor of local recurrence and poor prognosis. Transoral robotic surgery (TORS) has been developed for a panoramic view of the AC and en-bloc resection of the tumor by multidirectional dissection with endo-wristed instruments. With satisfactory preliminary results, we would like to update the data with a bigger cohort and present the news on using TORS for salvage treatment of recurrence from irradiation failure. METHODS: From July 2010 to December 2019, 22 patients with early T1 and 2 stage primary (n = 11) or recurrent (n = 11) glottic cancer with AC involvement received TORS without adjuvant therapy. TORS exposure was found to be better than TLM by conventional laryngoscopy in diagnostic biopsy. Seven of the 22 patients had recurrent cancer from irradiation failure. The perioperative factors that may be associated with survival were retrospectively analyzed, and the 5-year overall survival (OS)/disease-specific survival (DSS)/recurrence-free survival (RFS)/and organ preservation survival (OPS) rate were estimated by the Kaplan-Meier Method. Their voice and swallowing functions were evaluated by questionnaires of Voice Handicap Index-10 (VHI-10) and Functional Outcome Swallowing Scale (FOSS). RESULTS: All 22 TORSs were completed smoothly. After a mean follow-up of 49 ± 35.9 months, the Kaplan-Meier method estimated 5-year OS/DSS/RFS/OPS was 93.8%, 93.8%, 74.6%, and 86.3%, respectively. Our 11 patients with fresh cancer had 100% recurrence-free survival. Although the recurrent rate was higher in patients with history of RT, they could be rescued by further open laryngectomy without compromising the OS and DSS. Only one patient expired. The other 21 patients had satisfactory swallowing function with FOSS of 0.33 ± 0.66. Five patients depended on tracheostomy, but the rest 17 patients had serviceable voice with VHI-10 of 18.41 ± 11.29. CONCLUSIONS: TORS could be used in the primary or salvage management of glottic cancer with AC involvement while TORS was confirmed to have better exposure to TLM. The RFS was good for patients with primary cancer. In patients having irradiation failure, TORS could also be a minimally invasive transoral approach before trying open surgery to preserve the organ.

Predictive value of alarm symptoms in Rome IV irritable bowel syndrome: A multicenter cross-sectional study.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional bowel disease that shares features with many organic diseases and cannot be accurately diagnosed by symptom-based criteria. Alarm symptoms have long been applied in the clinical diagnosis of IBS. However, no study has explored the predictive value of alarm symptoms in suspected IBS patients based on the latest Rome IV criteria. AIM: To investigate the predictive value of alarm symptoms in suspected IBS patients based on the Rome IV criteria. METHODS: In this multicenter cross-sectional study, we collected data from 730 suspected IBS patients evaluated at 3 tertiary care centers from August 2018 to August 2019. Patients with IBS-like symptoms who completed colonoscopy during the study period were initially identified by investigators through medical records. Eligible patients completed questionnaires, underwent laboratory tests, and were assigned to the IBS or organic disease group according to colonoscopy findings and pathology results (if a biopsy was taken). Independent risk factors for organic disease were explored by logistic regression analysis, and the positive predictive value (PPV) and missed diagnosis rate were calculated. RESULTS: The incidence of alarm symptoms in suspected IBS patients was 75.34%. Anemia [odds ratio (OR) = 2.825, 95% confidence interval (CI): 1.273-6.267, P = 0.011], fecal occult blood [OR = 1.940 (95%CI: 1.041-3.613), P = 0.037], unintended weight loss (P = 0.009), female sex [OR = 0.560 (95%CI: 0.330-0.949), P = 0.031] and marital status (P = 0.030) were independently correlated with organic disease. The prevalence of organic disease was 10.41% in suspected IBS patients. The PPV of alarm symptoms for organic disease was highest for anemia (22.92%), fecal occult blood (19.35%) and unintended weight loss (16.48%), and it was 100% when these three factors were combined. The PPV and missed diagnosis rate for diagnosing IBS were 91.67% and 74.77% when all alarm symptoms were combined with Rome IV and 92.09% and 34.10% when only fecal occult blood, unintended weight loss and anemia were combined with Rome IV, respectively. CONCLUSION: Anemia, fecal occult blood and unintended weight loss have high predictive value for organic disease in suspected IBS patients and can help identify patients requiring further examination but are not recommended as exclusion criteria for IBS.

A topical fluorometholone nanoformulation fabricated under aqueous condition for the treatment of dry eye.

Fluorometholone (FMT) is a frequently prescribed drug for the alleviation of dry eye. However, due to low aqueous solubility, it has been routinely used as an ophthalmic suspension, which is characterized by low bioavailability, inconvenience of administration, and difficulty in delivering accurate dose. Furthermore, the opaque appearance of the ophthalmic suspension is not desirable for optical purpose. In the present study, a transparent FMT nanoformulation (FMT-CD NPs) was fabricated by the cyclodextrin (CD) nanoparticle technology without organic solvents. It was demonstrated that FMT was encapsulated in an amorphous form, which was associated with increased release rate and enhanced corneal penetration efficiency. The biocompatibility of FMT-CD NPs was confirmed by the Live/Dead assay, CCK-8 assay and the wound healing assay. Most importantly, FMT-CD NPs alleviated dry eye signs more efficiently than the commercial eye drop, with one-fifth the dosage of FMT in the latter. Collectively, our study provides a promising FMT formulation for improved management of dry eye while reducing drug related side effects.

Validation of the local applicability of the 'TIB' Olfactory Test Device in the era of COVID-19.

OBJECTIVE: To evaluate the validity and test-retest reliability of the novel 'TIB' Olfactory Test Device (TIB) and to determine its normative values. METHODS: The study stratified the study subjects into normosmic, hyposmic and anosmic groups according to their olfactory function. The olfactory function of the subjects was evaluated using both the traditional Chinese version of the University of Pennsylvania of Smell Identification Test (UPSIT-TC) and the TIB. The normosmic group was used to retest with the UPSIT-TC and TIB at an inter-test interval of at least 7 days. The cut-off scores of TIB among the three different groups were determined by receiver operating characteristic curve analysis. RESULTS: This study enrolled 180 subjects: 60 in each group. The mean scores of TIB were 44.1 for the normosmic group, 27.5 for the hyposmic group and 10.9 for the anosmic group. The TIB scores were significantly different across the three groups. There was a significant correlation between the first and second TIB tests (r = 0.506). The cut-off scores were 41 for normosmic subjects and 24 for hyposmic subjects. CONCLUSION: The validity and test-retest reliability results suggest that the TIB is an appropriate olfactory test for the Taiwanese population.

A Pilot Study of the Waterless Empirical Taste Test.

OBJECTIVES: This study was performed to test the clinical applicability of a new taste test-the waterless empirical taste test (WETT). METHODS: Sixty healthy volunteers and 20 patients with oral cancer were enrolled. They all received the conventional solution-based whole-mouth suprathreshold taste test (WMTT), which contained sucrose, citric acid, sodium chloride, and caffeine solutions for tastants, along with the WETT. The WETT used plastic strips to deliver tastants. The strip was embedded with sucrose, citric acid, sodium chloride, caffeine, or monosodium glutamate taste enhancer in 4 different concentrations. Each strip was tested twice. Thirty of the healthy volunteers received the WETT again to measure a retest reliability. Case-control matching by age and gender was used to compare the scores of WMTT and WETT between 13 healthy volunteers and 13 patients with oral cancer. RESULTS: The correlation was not high between the WMTT and WETT (r < 0.7) whether in the healthy volunteers or in patients with oral cancer. In terms of retest reliability of the WETT, the mean total score was 24.9 ± 7.3 for the first test and 25.8 ± 8.4 for the second test. The intraclass correlation coefficient was 0.85 (P < .001). When case-control matching was performed, the WMTT scores were not significantly different between 13 healthy volunteers and 13 patients with oral cancer (P = .266), but the WETT scores were significantly lower in patients with oral cancer (P = .017). CONCLUSION: This study showed that the results of the WETT were not highly correlated with those of the WMTT. However, its retest reliability was high, and its results were significantly different between the healthy volunteers and the patients with oral cancer.

Engineering Advanced Drug Delivery Systems for Dry Eye: A Review.

Dry eye disease (DED) is a widespread and frequently reported multifactorial ocular disease that not only causes ocular discomfort but also damages the cornea and conjunctiva. At present, topical administration is the most common treatment modality for DED. Due to the existence of multiple biological barriers, instilled drugs generally exhibit short action times and poor penetration on the ocular surface. To resolve these issues, several advanced drug delivery systems have been proposed. This review discusses new dosage forms of drugs for the treatment of DED in terms of their characteristics and advantages. Innovative formulations that are currently available in the market and under clinical investigation are elaborated. Meanwhile, their deficiencies are discussed. It is envisioned that the flourishing of advanced drug delivery systems will lead to improved management of DED in the near future.

Adeno-associated virus vector intraperitoneal injection induces colonic mucosa and submucosa transduction and alters the diversity and composition of the faecal microbiota in rats.

Background: Viral vector technology, especially recombinant adeno-associated virus vector (rAAV) technology, has shown great promise in preclinical research for clinical applications. Several studies have confirmed that rAAV can successfully transduce the enteric nervous system (ENS), and rAAV gene therapy has been approved by the Food and Drug Administration (FDA) for the treatment of the early childhood blindness disease Leber congenital amaurosis and spinal muscular atrophy (SMA). However, until now, it has not been possible to determine the effect of AAV9 on intestinal microbiota. Methods: We examined the efficiency of AAV9-mediated ascending colon, transverse colon and descending colon transduction through intraperitoneal (IP) injection, performed 16S rRNA gene amplicon sequencing and analysed specific faecal microbial signatures following AAV9 IP injection via bioinformatics methods in Sprague-Dawley (SD) rats. Results: Our results showed (1) efficient transduction of the mucosa and submucosa of the ascending, transverse, and descending colon following AAV9 IP injection; (2) a decreased alpha diversity and an altered overall microbial composition following AAV9 IP injection; (3) significant enrichments in a total of 5 phyla, 10 classes, 13 orders, 15 families, 29 genera, and 230 OTUs following AAV9 IP injection; and (4) AAV9 can significantly upregulate the relative abundance of anaerobic microbiota which is one of the seven high-level phenotypes that BugBase could predict. Conclusion: In summary, these data show that IP injection of AAV9 can successfully induce the transduction of the colonic mucosa and submucosa and alter the diversity and composition of the faecal microbiota in rats.