Self-Implantable Core-Shell Microneedle Patch for Long-Acting Treatment of Keratitis via Programmed Drug Release.

Bacteria-induced keratitis is a major cause of corneal blindness in both developed and developing countries. Instillation of antibiotic eyedrops is the most common management of bacterial keratitis but usually suffers from low bioavailability (i.e., <5%) and frequent administration, due to the existence of corneal epithelial barrier that prevents large and hydrophilic drug molecules from entering the cornea, and the tear film on corneal surface that rapidly washes drug away from the cornea. Here, a self-implantable core-shell microneedle (MN) patch with programmed drug release property to facilitate bacterial keratitis treatment is reported. The pH-responsive antimicrobial nanoparticles (NPs), Ag@ZIF-8, which are capable of producing antibacterial metal ions in the infected cornea and generating oxidative stress in bacteria, are loaded in the dissolvable core, while the anti-angiogenic drug, rapamycin (Rapa), is encapsulated in the biodegradable shell, thereby enabling rapid release of Ag@ZIF-8 NPs and sustained release of Rapa after corneal insertion. Owing to the programmed release feature, one single administration of the core-shell MN patch in a rat model of bacterial keratitis, can achieve satisfactory antimicrobial activity and superior anti-angiogenic and anti-inflammation effects as compared to daily topical eyedrops, indicating a great potential for the infectious keratitis therapy in clinics.

[Treatment of Rheumatoid Arthritis by Hebi Recipe: an Efficacy Observation].

OBJECTIVE: To observe the auxiliary efficacy and safety of Hebi Recipe (HR)in treating early rheumatoid arthritis (RA). METHODS: Totally 63 early RA patients with Gan-Pi disharmony were randomly assigned to the treatment group [32 cases, treated by HR (one dose per day, taken in two portions for 24 successive weeks) plus Methotrexate (MTX)] and the control group (31 cases, treated by MTX alone). The dosage of MTX was increased from 7.5 mg to 12.5 mg, once per week, 24 weeks as one course of treatment. Efficacy for Chinese medical syndromes, American College of Rheumatology 20 (ACR20) improvement rate, disease activity score in 28 joints (DAS28), laboratory related indices [ESR, rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide (CCP)], and related ultrasonic inspection items (synovium thickness, synovium blood flow classification, effusion of joint), and adverse reactions were observed. RESULTS: The total effective rate (83.9%, 26/31 cases) and ACR20 improvement rate (74.2%, 23/31 cases) were higher in the treatment group than in the control group [60.7% (17/28 cases), 46.4% (13/28 cases); P < 0.05]. Compared with before treatment in the same group, DAS28 score, ESR, RF, CRP, CCP, synovium thickness, synovium blood flow classification, effusion of joint all decreased in the two groups after treatment (P < 0.01, P < 0.05). Compared with the control group after treatment, ACR20 improvement rate, DAS28 score, ESR, RF, CRP, CCP, synovium thickness, synovium blood flow classification, effusion of joint all decreased in the treatment group (P < 0.01, P < 0.05). Liver dysfunction occurred in 1 case of the treatment group. One leucopenia and 2 liver dysfunction occurred in the control group. CONCLUSION: HR could effectively improve joints and systemic symptoms of early RA patients with Gan-Pi disharmony.

Comparative observation of the effectiveness and safety of remimazolam besylate versus dexmedetomidine in gastrointestinal surgery in obese patients.

BACKGROUND: Surgery for obese patients carries a higher risk of anesthesia complications compared with surgery for nonobese patients. Thus, a safe and effective anesthesia strategy is necessary to improve the medical experience of such patients and ensure their safety. AIM: To compared the effectiveness and safety of remimazolam besylate versus dexmedetomidine (DEX) in gastrointestinal surgery in obese patients. METHODS: The study cohort included 60 obese patients undergoing gastrointestinal surgery between July 2021 and April 2023, comprising 30 patients who received DEX intervention (control group) and 30 patients who received remimazolam besylate intervention (research group). Heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), blood oxygen saturation (SpO2), safety (nausea and vomiting, bradycardia, hypotension, and apnea), anesthesia and examination indices [induction time, anesthesia recovery time, and postanesthesia care unit (PACU) discharge time], sedation effect (Ramsay Sedation Scale), and postoperative pain visual analog scale were comparatively analyzed before anesthesia (T0), during anesthesia (T1), and after anesthesia (T2). RESULTS: At T1, the research group showed significantly smaller changes in HR, RR, MAP, and SpO2 than the control group, with a significantly lower adverse reaction rate and shorter induction, anesthesia recovery, and PACU discharge times. Additionally, the intra- and postoperative Ramsay Sedation Scale scores were statistically higher in the research group than in the control group. CONCLUSION: Remimazolam besylate was significantly more effective than DEX in gastrointestinal surgery in obese patients and had a higher safety profile and value in clinical promotion.

Effects of repetitive transcranial magnetic stimulation on neuropathic pain: A systematic review and meta-analysis.

Neuropathic pain (NP) is a chronic pain condition caused by lesion or disease of the somatosensory nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a neuroregulatory tool that uses pulsed magnetic fields to modulate the cerebral cortex. This review aimed to ascertain the therapeutic effect of rTMS on NP and potential factors regulating the therapeutic effect of rTMS. Database search included Web of Science, Embase, Pubmed, and Cochrane Library from inception to July 2021. Eligible studies included randomized controlled studies of the analgesic effects of rTMS in patients with NP. Thirty-eight studies were included. Random effect analysis showed effect sizes of -0.66 (95 % CI, -0.87 to -0.46), indicating that real rTMS was better than sham condition in reducing pain (P < 0.001). This comprehensive review indicated that stimulation frequency, intervention site, and location of lesion were important factors affecting the therapeutic effect. The findings of this study may guide clinical decisions and future research.

Ultrasound-guided percutaneous microwave ablation for symptomatic uterine fibroid treatment--a clinical study.

OBJECTIVE: The aim of this study was to assess the feasibility, safety and therapeutic effects of ultrasound (US)-guided percutaneous microwave thermal ablation (PMTA) in situ for the treatment of symptomatic uterine fibroid. MATERIALS AND METHODS: The microwave (MW) antenna was percutaneously inserted into the fibroid under US guidance to perform the ablation. The ultrasound images, any complications and side effects were assessed during and after ablation. The shrinkage rate of the fibroid was calculated after the treatment. RESULTS: Forty patients underwent the treatment. The baseline fibroid volume was 14.6 to 341.1 cm(3) (mean 140.1 ± 87.4 cm(3)). When the MW therapy started, a heightened echo around the MW emission aperture of the antenna was observed and gradually propagated throughout the fibroid while the ablation continued. The mean ablation time was 490 s. Contrast enhanced MRI showed no enhancement in the fibroid post-ablation. The shrinkage rate of the fibroid was 61.8%, 78.7%, 73.2% and 93.1% at 3, 6, 9, and 12 months after ablation, respectively. Six patients felt pain in their lower abdomens or waists within 12 hours post-ablation, and the discomfort rapidly disappeared. Seven patients had a small amount of vaginal bloody secretions within one to two weeks after treatment, and six of these patients recovered from the bleeding without any therapy after one week. No patient developed complications and fever during or after the ablation. CONCLUSIONS: PMTA for fibroid is feasible and safe, and it is an easy and fast procedure that is minimally invasive.

Successful repair for a ruptured venous aneurysm: an unusual complication of venous arterialization in Buerger's disease.

We report a ruptured venous aneurysm, an unusual complication of venous arterialization for lower limb ischemia in Buerger's disease. Arteriovenous shunt ligation and aneurysm resection were performed successfully, with the distal limb perfusion preserved. By our very limited experience, venous arterialization may be ineffective on improving lower limb ischemia with Buerger's disease.

Therapeutic options and drug delivery strategies for the prevention of intrauterine adhesions.

Intrauterine adhesions (IUAs) are bands of fibrous tissue that form in the endometrial cavity and associated with the increased risk of abnormal menstruation, recurrent pregnancy loss, secondary infertility, and pregnancy complications. Physical barriers, including intrauterine device and hydrogel, were clinical available to prevent the post-operational IUAs. But physically separation of the injured endometrium relies on the own limited healing power and often ends with recurrence. In recent years, the mechanisms driving IUAs treatment has validated the application of hormones, and further stem cell therapy has also led to the development of novel therapeutic agents with promising efficacy in pre-clinical and initial clinical studies. Still, it is challenging to delivery the therpaeutic factors to the injured uterus. Herein, in this review, we discuss the traditional intervention methods for the prevention of IUAs, as well as novel therapeutics and delivery strategies that will most likely change the treatment paradigms for better clinical outcomes. The combination strategy that using physical barriers as the delivery carriers for therapeutics might provide new alternatives for the prevention of IUAs.

[NSAIDs combined with radiotherapy to prevent heterotopic ossification after total hip arthroplasty].

OBJECTIVE: To investigate the preventive effects and differences of NSAIDs combined with radiotherapy, NSAIDs and radiotherapy for heterotopic ossification(HO) after total hip arthroplasty(THA). METHODS: From February 2015 to July 2016, 168 hips undergoing primary THA were divided into group A, B and C, and 163 patients were followed up (54 cases and 54 hips in group A, 55 cases and 55 hips in group B, 54 cases and 54 hips in group C). Among group A, 5 hips were primary osteoarthritis, 37 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 12 hips were secondary osteoarthritis due to acetabular dysplasia. Patients in group A received oral celecoxib (0.2 g, 2 times a day) for 2 weeks after operation. Among group B, 6 hips were primary osteoarthritis, 32 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 17 hips were secondary osteoarthritis due to acetabular dysplasia, all of which in group B were treated with preoperative single 7 Gy radiotherapy. Among group C, 5 hips were primary osteoarthritis, 35 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 14 hips were secondary osteoarthritis due to acetabular dysplasia. Patients in group C were treated with preoperative radiotherapy and celecoxib after operation. The side effects of gastrointestinal reactions were observed after operation, and the heterotopic ossification was evaluated by pelvic anterior and posterior X-ray (Brooker grading). RESULTS: The mean clinical and radiological follow-up was 21 months(12 to 30 months). In group A, 54 hips were followed up with 7 hips with heterotopic ossification, including 5 hips of Brooker I and 2 hips of Brooker II. In group B, 55 hips were successfully followed up, with 8 hips of heterotopic ossification occurred, including 6 hips of Brooker I, 2 hips of Brooker II. In group C, 54 hips were successfully followed up, with 5 hips of heterotopic ossification occurred , including 4 hips of Brooker I, 1 hip of Brooker II. There was no significant difference in efficacy among 3 groups (χ²=0.743, P=0.690) by chi-square test. The prevalence of side effects were as following: in group A, there were 6 hips with side effects;in group B, there were 6 hips with side effects;in group C, there were 7 hips with side effects. There was also no significant difference in side effects among 3 groups (χ²=0.135, P=0.935). CONCLUSIONS: The combined-therapy group has lower prevalence of HO than the NSAIDs group or radiotherapy group, but the statistical difference between them is not significant. NSAIDs is still the first choice to prevent HO after THA.

[Effects on electro-scaip acupuncture on cerebral dopamine transporter in patients with Parkinson' s disease].

OBJECTIVE: To investigate the effect of electro-scalp acupuncture (ESA) on dopamine transporter (DAT) in basal ganglia (BG) of patients with Parkinson's disease (PD) by single photon emission computed tomography (SPECT). METHODS: Ten patients with primary PD were divided equally into two groups randomly. Patients in the treated group received ESA at points of MS6, MS4, MS8, MS9 and MS14, for patients with unilateral lesions, ESA was applied on contralateral points, while for those with bilateral lesions, points of both sides were stimulated, the depth of puncturing was made to arrive at the galea aponeurotica. Patients in the control group took medopa orally in the dosage of 125 mg, 3 times per day for mild, 250 mg, 3 times per day for moderate and 250 mg, 4 times per day for severe cases. All the patients were examined with 99mTc-TRODAT- 1 SPECT before and after 6 weeks' treatment to analyze the activity of DAT by ratio of basal ganglia/occipital (BG/OC) using regional of interesting (ROI) technique. RESULTS: The uptake of 99mTc-TRODAT-1 increased after treatment in both groups. In the treated group, the homolateral (of the affected limbs, the same below) BG/OC ratios before and after treatment were 1.1883 +/- 0.1471 and 1.2416 +/- 0.3146 respectively, and those in the control group 1.1597 +/- 0.0568, 1.2053 +/- 0.1153, showing no significant difference between them (P > 0.05); while the contralateral BG/OC ratios before and after treatment were 0.9019 +/- 0. 1210 and 0.9496 +/- 0.2522 respectively in the treated group, and 1.0436 +/- 0.1393 and 1.2972 +/- 0.2612 respectively in the control group. The difference value of contralateral BG/OC before and after treatment in the control groups was significantly different (P<0.05). But at other cerebral regions, 99mTc-TRODAT-1 SPECT showed no difference between the two groups in changes before and after treatment, therefore, showed no difference in effect of improving DAT between the two groups (P > 0.05). CONCLUSION: ESA could reduce the loss of DAT in basal ganglia and improve its activity in patients with PD to protect the dopamine neuron, so as to delay the progression of PD and alleviate clinical symptoms of patients.

Sulfur fumigation, a better or worse choice in preservation of Traditional Chinese Medicine?

Sulfur fumigation (SF) in Traditional Chinese Medicine (TCM) is a highly efficient and important traditional preservation method in China. This method has generated a great deal of concern and has been disputed in the last few years because of its uncertain safety. SF can alter the quality of TCMs by damaging the bioactive compounds, changing chemical profiles, and generating detrimental exogenous materials. However, SF is still widely used in the herbal medicinal industry because of its various benefits, such as its pesticidal and anti-bacterial effects, easy operation, and low-cost. This review contains the current situation, chemical mechanism and reactions during SF, the pharmacological and pharmacokinetic research, and the influence of quality caused by SF. In addition, a quantification-operation sulfur fumigation device (QOSFD), which can maintain the quality of TCMs by controlling the SF processing parameters, has been designed and introduced. The key technologies of this device involve controlling the O(2) content and the temperature of SO(2) as well as the quantification of sulfur in SF. This device can reduce the possibility of reaction between bioactive compounds and sulfur/sulfurous acid, as well as control the limitation of SO(2) residues. The QOSFD is regarded as a promising preservation technique in the field of TCM, medicinal materials, agriculture, and fruit industry.

[Epidemiological effects of the A (H1N1) influenza vaccine immunization program on students].

OBJECTIVE: To evaluate the epidemiological effects of vaccine immunization program related to A (H1N1) influenza in the middle school students. METHODS: Non-randomized clinical trial was designed to assess the A (H1N1) influenza vaccine on its efficacy. 14 883 students from 8 middle schools in Zhejiang province were recruited and classified into vaccinated or control groups, based on the status of immunization with A (H1N1) influenza vaccine. All subjects were followed up through one epidemic period (6 months) and the incidence rates of influenza-like illnesses, A (H1N1) influenza, and seasonal influenza in these two groups were compared to evaluate the efficacy of the vaccine. RESULTS: There were 6334 subjects in the vaccinated group and 8549 in the control group. 7441.75 person-years were followed from these two groups. The incidence rate of A (H1N1) influenza in vaccinated group was 1.64‰ per person-year, lower than that of the control group. The rate difference (RD) was -1.64‰ per person-year (95% confidence interval value from -3.04‰ to -0.23‰ per person-year), and the difference was significant (P = 0.010). The incidence rate of influenza-like illnesses in vaccinated group was 21.47‰ per person-year, lower than that of the control group (22.69‰ per person-year) and the difference was not significant (P > 0.05). The incidence rate of B influenza in vaccinated group was 6.63‰ per person-year, higher than that of control group (7.02‰ per person-year) but the difference was not significant (P > 0.05). CONCLUSION: This vaccine demonstrated a good epidemiological effect against the A (H1N1) influenza virus infection, observed through a student-immunization program. The cross-protection effect against the influenza-like illnesses and other seasonal influenzas was not noticed in this study.