Objective:To investigate the clinical application effect of double-layer soft tissue(DLST)suture closure technique in patients with mandible medication-related osteonecrosis of the jaw(MRONJ)of early and medium stages resulted in application of anti-bone-resorptive drugs.Methods:Early to me-dium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking Uni-versity School and Hospital of Stomatology from October 2021 to September 2022 were included.Clinical information of the patients were collected,including primary disease,concomitant disease,medication regimen(drug type,duration of medication),MRONJ stage,clinical symptoms,imaging manifestations,etc.During surgery,after using marginal mandibulae resection to remove the necrotic bone,the wound was closed using DLST closure technique.Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique,the pain score and functional status of the patiens were evaluated.Results:This study totally included 13 patients,12 women and 1 man,aged(66.69±13.14)years.Seven patients had osteoporosis,2 had lung cancer,3 had breast cancer and 1 had prostate cancer among their primary diseases;7 had no concomitant diseases,2 had diabetes melli-tus,2 had cardiovascular disease and 1 had dry syndrome.Intravenous zoledronic acid were used in 9 patients,the average duration was(37.7±20.0)months,and other drugs,such as letrozole tablets were taken in 7 patients at the same time;Denosumab injection was used in 3 patients for an average of(10.3±11.9)months;Alendronate sodium tablets were taken in 5 patients for an average of(55.20± 27.20)months,and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 pa-tients.The average post-operative follow-up was 11.9 months(9 to 17 months),and all the 13 patients were cured without complications,such as pus overflow and so forth.The pre-operative score of Karnof-sky performance status(KPS)in the patients was 68.46±14.05,and the post-operative score was 82.31±15.36,and the difference was statistically significant(P＜0.05).The pre-operative score of visual analogue scale(VAS)in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51,and the difference had statistical significance(P＜0.001).Conclusion:The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the man-dible using anti-bone-resorptive drugs alone,and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

Herpes zoster of trigeminal nerve was a common skin disease caused by varicella-zoster virus infection.Simple involvement of the third branch of trigeminal nerve was rare,and so were oral complica-tions such as pulpitis,periodontitis,spontaneous tooth loss,bone necrosis,etc.This article presented a case of herpes zoster on the third branch of the left trigeminal nerve complicated with left mandibular osteonecrosis.We reported the case of a 64-year-old man with sudden pain in the left half of the tongue 1 month ago,and then herpes on the left facial skin appeared following with acute pain.The local hospital diagnosed it as herpes zoster and treated it with external medication.A few days later,he developed gum pain in the left mandibular posterior tooth area.He was admitted to Peking University School and Hospital of Stomatology one week ago with loose and dislodged left posterior tooth accompanied by left mandibular bone surface exposure.Clinical examination showed bilateral symmetry and no obvious restriction of mouth opening.Visible herpes zoster pigmentation and scarring on the left side of the face appeared.The left mandibular posterior tooth was missing,the exposed bone surface was about 1.5 cm x0.8 cm,and the surrounding gingiva was red and swollen,painful under pressure,with no discharge of pus.The re-maining teeth in the mouth were all m degree loosened.Imageological examination showed irregular low-density destruction of the left mandible bone,unclear boundary,and severe resorption of alveolar bone.The patient was diagnosed as left mandibular osteonecrosis.Under general anesthesia,left mandibular le-sion exploration and curettage+left mandibular partial resection+adjacent flap transfer repair were performed.The patient was re-exmained 6 months after surgery,there was no redness,swelling or other abnormality in the gums and the herpes pigmentation on the left face was significantly reduced.Unfortu-nately,the patient had complications of postherpetic neuralgia.This case indicate that clinicians should improve their awareness of jaw necrosis,a serious oral complication of trigeminal zoster,and provide ear-ly treatment.After the inflammation was initially controlled,surgical treatment could be considered to remove the necrotic bone,curettage the inflammatory granulation tissue,and extraction of the focal teeth to avoid further deterioration of the disease.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

Objective:This study investigated the changes of cortical thickness in patients with Parkinson's cognitive dysfunction.Methods:In this cross-sectional study, general clinical data and head magnetic resonance imaging data were collected from Parkinson's disease(PD)patients and healthy controls who were hospitalized or outpatient in the Department of Geriatric Neurology of the First Affiliated Hospital of Kunming Medical University from January 2019 to December 2020.We observed the changes of cortical thickness in each group, and analyzed the correlation between cortical thickness and cognitive dysfunction in PD.Results:Compared with PD normal cognitive group, the cortical thickness of the left superiortemporal gyrus[(2.7±0.1)mm, (2.4±0.1)mm, t=-4.194], left supramarginal[(2.4±0.1)mm, (2.2±0.1)mm, t=-4.845], right insula[(3.0±0.1)mm, (2.7±0.1)mm, t=-4.170], left parahippocampal[(2.8±0.3)mm, (2.4±0.3)mm, t=-4.164]decreased in PD cognitive impairment group(all P<0.05), and cortical thickness of the right parsorbitalis[(2.5±0.2)mm, (2.4±0.2)mm, t=-4.226], left entorhinal[(3.5±0.3)mm, (3.1±0.4)mm, t=-4.583], left inferiortemporal[(2.7±0.2)mm, (2.5±0.1)mm, t=-6.229], left supramarginal[(2.4±0.1)mm, (2.1±0.1)mm, t=-3.236], right fusiform[(2.8±0.1)mm, (2.5±0.1)mm, t=-5.364], right lingual[(2.0±0.1)mm, (1.9±0.1)mm, t=-3.887], right insula[(3.0±0.1)mm, (2.7±0.2)mm, t=-5.326], right isthmuscingulate[(2.6±0.2)mm, (2.3±0.2)mm, t=-3.743]decreased in PD severe cognitive impairment group, the statistical difference was significant(all P<0.05). The cerebral cortex thickness was positively correlated with Mini-Mental State Examination and different cognitive areas, and negatively correlated with Hoehn-Yahrr grading. Conclusions:Local cortical thinning was observed in PD patients with cognitive impairment, whereas cortical involvement was more extensive in PD patients with severe cognitive impairment.

Objective:To investigate the relationship between rapid eye movement sleep behavior disorder(RBD)and neurofilament light chain(NfL)levels in patients with Parkinson's disease(PD).Methods:General clinical data of 121 PD patients and 38 healthy controls(HC)who visited the Department of Geriatric Neurology of the First Affiliated Hospital of Kunming Medical University from June 2019 to January 2021 were collected in a prospective study.According to the Rapid Eye Movement Sleep Behavior Disorder Questionnaire(RBDSQ), PD patients were divided into a PD with RBD group(PD-RBD, RBDSQ≥6)and a PD without RBD group(PD-NRBD, RBDSQ<6). General clinical data and plasma NfL levels of patients in the groups were compared.In addition, symptoms during exercise, during non-exercise, and sleep quality in the groups were also compared.Results:Plasma NfL levels were higher in the PD group than in the HC group(19.39 ng/L, 12.58-31.78; 14.85 ng/L, 9.78-22.15; Z=-2.492, P<0.05); plasma NfL levels were significantly higher in the PD-RBD group than in the PD-NRBD group and in the HC group(25.29 ng/L, 19.09-34.75; 17.14 ng/L, 11.70-26.67; 14.85 ng/L, 9.78-22.15; Z=-3.434, P<0.01); there was no significant difference in plasma NfL levels between the HC group and the PD-NRBD group( P>0.05). Receiver operating characteristic(ROC)curve analysis showed that, when the plasma NfL cutoff was set at 17.86 ng/L, PD-RBD and PD-NRBD could be distinguished( AUC=0.70, 95% CI=0.60-0.80, sensitivity 82%, specificity 54%). Binary logistic regression identified NfL level as an independent predictor of PD-RBD( β=0.068, OR=1.103, P=0.003). Conclusions:PD-RBD patients have increased plasma NfL levels, which can potentially serve as a biomarker for PD with RBD.

Objective:To observe the clinical features and visual prognostic factors of ethambutol-induced optic neuropathy (EON).Methods:A cohort study. Twenty-four inpatients (46 eyes) identified as EON in Neuro-Ophthalmology Department of Chinese PLA General Hospital from January 2014 to December 2017 were enrolled, including 14 males (26 eyes) and 10 females (20 eyes) with a ratio of 1.4/1 male/female. The average age was 42.79±15.12 years and the average weight was 62.46±12.31 kg. The average time duration between oral administration of ethambutol and occurrence of EON was 9.94±16.49 months. The average time of ethambutol duration was 7.06±11.68 months, with an average accumulative dose of 156.7±1 779.0 g and the average daily dose of 15.07±8.95 mg/(kg·d). All patients were tested with visual acuity, fundus photos, colour vision, OCT, visual field, VEP, orbital MRI and the gene of OPA1 and mitochondrial deoxyribonucleic acid(mtDNA). All the patients accepted drug withdrawal immediately after diagnosis, and were given the treatment of systemic nerve nutrition and improvement of microcirculation for 2 weeks. The time of follow-up was more than 12 months. According to whether the visual acuity (VA) in any of eyes was over than 0.1 at the last follow- up, all the patients were divided into two groups: the bad VA group (VA less than or equal to 0.1) and the better VA group (VA over than 0.1) group. The χ2 test and Fisher's exact probabilistic method test were used to compare the counting data between groups, and the Wlincox rank sum test was used to compare the measurement data. Multiple factors of VA outcome between the patients with bad or better va were analyzed by logistic regression. Results:Thirty eyes (65.2%) had VA less than or equal to 0.1 and 5 eyes (10.9%) had VA over than 0.5 at EON onset. The VA of the rest 11 eyes (23.9%) was higher than 0.1 and lower than 0.5. At the last follow- up, 20 eyes (43.5%) had VA less than or equal to 0.1 and 9 eyes (19.6%) had VA over than 0.5, the VA of the rest 17 eyes (36.9%) was higher than 0.1 and lower than 0.5. Fundus examination revealed 7 eyes (15.3%) with optic disc edema. OCT revealed significant loss of the retinal nerve fiber layer (RNFL) in the affected eyes, mainly in the temporal RNFL of the optic disc. All patients had dyschromasia, mainly in distinguishing the color of red and green. The types of visual field defect was as following: central dark spot (52.2%), diffuse visual acuity decreased (30.4%), temporal hemianopsia (17.4%). Orbital MRI revealed that 12/24 (50.0%) patients had T2 lesions with T1 enhancement in 6/24 patients (25.0%). Genetic test showed that 4 patients (16.7%) had gene mutation. Among them, there were 2 patients with OPA1 mutation, 1 with mtDNA 14340 point mutation and 1 with the mtDNA 11778 point mutation. Thirteen patients showed better VA outcomes (over than 0.1) while 11 showed bad VA outcomes after discontinuation of ethambutol. Between the better VA group and the bad VA group, there were statistically significant differences in the daily dose of ethambutol and gene mutation( P=0.031, 0.023). The daily dose was related to visual prognosis of EON while only the daily dose of more than 18 mg/(kg·d) may lead to bad VA outcomes according to the logistic analysis (95% CI 0.007-0.736, OR=0.069, P=0.027). Conclusions:EON may have OPA1 and mtDNA mutation with more bilateral eyes involved and less optic edema, which about 43.5% of the patients showed irreversible visual impact. The daily dose of ethambutol is related to the vision recovery.

Malignant tumor has become an urgent threat to global public healthcare. Because of the heterogeneity of tumor, single therapy presents great limitations while synergistic therapy is arousing much attention, which shows desperate need of intelligent carrier for co-delivery. A core‒shell dual metal-organic frameworks (MOFs) system was delicately designed in this study, which not only possessed the unique properties of both materials, but also provided two individual specific functional zones for co-drug delivery. Photosensitizer indocyanine green (ICG) and chemotherapeutic agent doxorubicin (DOX) were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform. Except for efficient drug delivery, the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy. The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared (NIR) light irradiation. The

Pulmonary drug delivery has attracted increasing attention in biomedicine, and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs. However, the existing methods for preparing porous particles using porogens have several drawbacks, such as the inhomogeneous and uncontrollable pores, drug leakage, and high risk of fragmentation. In this study, a series of cyclodextrin-based metal-organic framework (CD-MOF) particles containing homogenous nanopores were delicately engineered without porogens. Compared with commercial inhalation carrier, CD-MOF showed excellent aerosolization performance because of the homogenous nanoporous structure. The great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments, including cytotoxicity assay, hemolysis ratio test, lung function evaluation,

Objective:To analyze the anatomical morphological characteristics of the trabecular bone of human mandibular condyle by observing the distribution of volume of interests (VOI).Methods:The micro-CT images of a right condyle specimen of a 61-year-old adult male was analyzed in this study. The cylindrical VOI with both diameter and height of 2 mm were arranged, according to a certain pattern, as many as possible at various levels within the trabecular bone of the condyle. Each VOI had no intersection area. The selected VOI were divided into 5 parts: medial part, middle part, lateral part, anterior part and posterior part, with 6 layers from top to bottom. And the distribution of the overall anatomical morphological characteristics of three-dimensional (3D) images of the trabecular bone of the condyle was analyzed by using seven morphological parameters of each VOI, i.e. bone mineral density (BMD), bone volume/total volume (BV/TV), bone surface area/bone volume (BS/BV), trabecular thickness (Tb.Th), trabecular bone number (Tb.N), trabecular spacing (Tb.Sp) and trabecular bone pattern factor (Tb.Pf).Results:In the present study, totally 34 VOI were selected from the condyle specimen.The morphological distribution of the VOI was uneven in the 3D structure of the trabecular bone of the human condyle. BMD, BV/TV, Tb.N and Tb.Th were much higher at the middle part, while showed the smallest at the medial part. The anterior part demonstrated much higher parameters than the posterior part at the first, second, fifth and sixth layers, respectively, however, the posterior part showed much higher parameters than the anterior part at the third and fourth layers, respectively. The BMD was much higher at the first [(332.66±97.11) mg/cm 3] and sixth [(255.79±45.68) mg/cm 3] layers, while the lowest at the second layer [(255.79±41.06) mg/cm 3]. The BV/TV and Tb.N were much higher at the first layer, with the lowest at the fifth layer. The Tb.Th at the first layer [(0.11±0.03) mm] was much higher than the others, which were similarly lower. The BS/BV, Tb.Sp and Tb.Pf were lower at the first layer and much higher at the medial and lateral parts, while were lower at the middle and anterior parts. The posterior part demonstrated much higher BS/BV, Tb.Sp and Tb.Pf than the anterior part at the first, fifth and sixth layers, respectively. However, the anterior part showed much higher scores than the posterior part at the third and fourth layers, respectively. The ANOVA results showed that the 7 morphological parameters of VOI were not statistically significant amongst the 6 layers ( P>0.05). However, the 6 out of the 7 parameters, i.e. BV/TV, BS/BV, Tb.Th, Tb.N, Tb.Sp and Tb.Pf, were statistically significant amongst the five parts ( P<0.05), while the only parameter of BMD was not statistically significant ( P>0.05). Conclusions:The anatomical distribution characteristics of the trabecular bone of condyle were analyzed by using 3D imaging measurement based on the VOI. The results showed uneven distributions and indicated that the method of dividing the trabecular bone of mandibular condyle into VOI sets, which accorded with its specific anatomical characteristics, was feasible for further reference.

Dissolving microneedles carried drug molecules can effectively penetrate the stratum corneum of skin to improve the transdermal drug delivery. The traditional Chinese medicine acupuncture is based on the needle stimulation at a specific location (acupoint) to generate and transmit biochemical and physiological signals which alter the pathophysiological state of patients. However, the pain associated with conventional acupuncture needles and the requirement of highly trained professionals limit the development of acupuncture in non-Asian countries. The purpose of this study is to investigate whether the dissolving microneedles can be utilized as a self-administered painless replacement for acupuncture and locally released drug molecules can achieve expected therapeutic outcomes. Immunosuppressive rats were treated with acupuncture at Zusanli (ST36) acupoint using microneedles containing thymopentin. The immune functions and psychological mood of the immunosuppressed animals were examined. The proliferation of splenocytes was examined by CCK-8 assay. CD4 and CD8 expression patterns in spleen cells were detected by flow cytometry. The current study showed that use of either microneedles containing thymopentin or conventional acupuncture both resulted in immune cell proliferation, which was confirmed by flow cytometry. Furthermore, either conventional acupuncture or microneedles were able to effectively mitigate the anxiety caused by immune-suppression when applied on the ST36.