Photothermal-Controllable Microneedles with Antitumor, Antioxidant, Angiogenic, and Chondrogenic Activities to Sequential Eliminate Tracheal Neoplasm and Reconstruct Tracheal Cartilage.

The optimal treatment for tracheal tumors necessitates sequential tumor elimination and tracheal cartilage reconstruction. This study introduces an innovative inorganic nanosheet, MnO2 /PDA@Cu, comprising manganese dioxide (MnO2 ) loaded with copper ions (Cu) through in situ polymerization using polydopamine (PDA) as an intermediary. Additionally, a specialized methacrylic anhydride modified decellularized cartilage matrix (MDC) hydrogel with chondrogenic effects is developed by modifying a decellularized cartilage matrix with methacrylic anhydride. The MnO2 /PDA@Cu nanosheet is encapsulated within MDC-derived microneedles, creating a photothermal-controllable MnO2 /PDA@Cu-MDC microneedle. Effectiveness evaluation involved deep insertion of the MnO2 /PDA@Cu-MDC microneedle into tracheal orthotopic tumor in a murine model. Under 808 nm near-infrared irradiation, facilitated by PDA, the microneedle exhibited rapid overheating, efficiently eliminating tumors. PDA's photothermal effects triggered controlled MnO2 and Cu release. The MnO2 nanosheet acted as a potent inorganic nanoenzyme, scavenging reactive oxygen species for an antioxidant effect, while Cu facilitated angiogenesis. This intervention enhanced blood supply at the tumor excision site, promoting stem cell enrichment and nutrient provision. The MDC hydrogel played a pivotal role in creating a chondrogenic niche, fostering stem cells to secrete cartilaginous matrix. In conclusion, the MnO2 /PDA@Cu-MDC microneedle is a versatile platform with photothermal control, sequentially combining antitumor, antioxidant, pro-angiogenic, and chondrogenic activities to orchestrate precise tracheal tumor eradication and cartilage regeneration.

[Bronchoscopic manifestations and interventional treatment of pulmonary mucormycosis].

Objective: To analyze the bronchoscopic manifestations and interventional treatment of pulmonary mucormycosis. Methods: Clinical data of patients with pulmonary mucormycosis undergoing bronchoscopy and interventional therapy in 4 tertiary general hospitals in China from May 2006 to May 2022 were retrospectively analyzed and the literature on the subject were reviewed. Results: The data of 10 patients with pathologically diagnosed pulmonary mucormycosis undergoing bronchoscopy and interventional therapy were collected, including 8 males and 2 females. The patients' age ranged from 21 to 72 (44±15) years. The underlying diseases included 6 cases of diabetes ketoacidosis, 3 cases of leukemia, 1 case after operation of lung cancer. Bronchoscopy showed that white viscous necrotic matters grew along the airway and blocked the airway in 9 cases, accompanied by airway bleeding in 3 cases, bloody secretion blocked the airway in 1 case, and bronchopulmonary cavity fistula in 2 cases. The biopsy histopathology of white necrotic matters showed that many mucor filaments were tangled together which were named mucormycelium. Among the 10 patients, 9 were treated with systemic drugs, including intravenous application of amphotericin B deoxycholate in 5 cases, intravenous application of amphotericin B liposome in 4 cases, oral posaconazole in 6 cases and intravenous injection in 1 case. Local drug therapy included aerosol inhalation of amphotericin B deoxycholate in 8 cases and local perfusion under bronchoscope in 5 cases. Bronchoscopic interventional therapy was used to remove mucormycelium in the bronchus, including cryotherapy in 8 cases, biopsy forceps in 7 cases, snare treatment in 2 cases and foreign body forceps in 2 cases. All 10 patients were clinical cured and with no death. Conclusions: Pulmonary mucormycosis is more common in immunocompromised hosts. Bronchoscopy often showed mucormycelium blocking the airway. Systemic and local drug therapy combined with bronchoscopic interventional therapy can achieve good clinical efficacy.

[Clinicopathological features of spinal solitary fibrous tumor].

Objective: To investigate the clinicopathological, molecular genetic, immunohistochemical and prognostic features of spinal solitary fibrous tumor (SFT). Methods: The clinical data of 12 cases of spinal SFT in Beijing Tsinghua Changgung Hospital, Affiliated to Tsinghua University, diagnosed from January 2015 to December 2021 were collected and reclassified. The clinical data, histopathology, immunohistochemistry and molecular genetics were analyzed. Follow-up and related literature reviews were conducted. Results: Among the 12 patients, there were 5 males and 7 females; the age ranged from 31 to 73 years, with a median age of 50.5 years. All 12 cases were primary tumors, including 4 cases diagnosed at the first time and 8 recurrent cases. Among the 12 cases, 8 were WHO grade 1, 3 were WHO grade 2, and 1 was WHO grade 3. Microscopically, the spinal SFT appeared as a spindle cell tumor, the stroma was rich in many thin-walled blood vessels with various histological features such as cell morphology and necrosis according to the different tumor grade. All (12/12) of the cases expressed vimentin and STAT6 (diffuse and strong nuclear stain), 11 cases (11/12) expressed both CD34 and bcl-2, and 7 cases (7/12) expressed CD99. Next-generation sequencing showed that 12 (12/12) of the patients had NAB2-STAT6 gene fusion. The 12 patients were followed up for 6 to 80 months. There were no recurrences or metastases in the 4 first cases after operation. Among the 8 recurrent cases, 2 of the patients relapsed and 2 died. Conclusions: Spinal SFT is rare and has a high recurrence tendency. Many aspects need to be considered in the diagnosis process. STAT6 is a relatively specific marker for the diagnosis of this tumor. Complete surgical resection is the preferred treatment while postoperative radiotherapy is recommended to reduce tumor recurrence.

[Transcriptome profiling of differentiated lenses through RNA sequencing].

Objective: To gain insight into the transcriptional landscape including mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) of the differentiated lens. Methods: Experiment research. The total RNAs of the differentiated lenses were extracted and purified. Total RNAs of 16-week, 23-week, and 25-week differentiated lenses were then sequenced using Illumina HiSeq 2500, and analyzed using bioinformatics tools. The top expressed and differentially expressed mRNAs and lncRNAs were screened. The expressions of overlap genes among the 16-week, 23-week, and 25-week lenses were analyzed by Venn diagram. The expression tendency of lens-specific genes was obtained and verified with real-time polymerase chain reaction. Results: A total of 67 518 311 mapped reads were obtained from differentiated lenses at 16 weeks, 99 440 160 at 23 weeks, and 67 262 320 at 25 weeks. The gene overlap expression analysis showed 740 of the top 1 000 highly expressed mRNAs, 170 of the top 300 highly expressed lncRNAs, and 69 of the top 100 highly expressed circRNAs overlapping expressed in lenses at 16, 23, and 25 weeks, respectively. Lens specific gene expression analysis revealed that the expression of crystallin (CRY) AA, CRYGA, CRYGB, CRYGC, CRYGD, CRYGEP, and CRYGS was upregulated, while the expression of gap junction (GJ) A3 and GJA8 was downregulated with the differentiation of lenses. Conclusion: The lens transcriptome profile shows that more than half of the high expressed mRNA, lncRNA and circRNA at different differentiation stages are overlapping expressed, and all of them have high expression of lens specific protein genes, such as CRY, GJ etc. (Chin J Ophthalmol, 2020, 56: 356-363).

[Changes of serum markers in acute liver injury induced by oral 1, 2-dichloropropane in BALB/cA-nu mice].

Objective: To investigate the characteristics of inflammatory response in BALB/cA-nu mice induced by oral 1, 2-dichloropropane (1, 2-DCP) , and to provides theoretical reference for further study of subchronic, chronic toxicity and carcinogenic mechanism. Methods: From October 2018, Clean grade healthy BALB/cA-nu mice were randomly divided into 5 groups with 10 mice in each group. And 860, 1150, 1500, 1950, 2535 mg/kg 1, 2-DCP were given by gavage respectively. Meanwhile, blank group and solvent control group (corn oil) were set up. Blood samples were collected from eyeballs and liver and bile tissues were collected for histopathological examination within 24 hours after exposure. The expression of alanine aminotransferase (ALT) , total bilirubin (TBLI) , C-reactive protein (CRP) , interleukin-6 (IL-6) , tumor necrosis factor-α (TNF-α) and tumor necrosis factor-ß (TNF-ß) were detected by enzyme-linked immunosorbent assay. Results: With the increase of the dose of 1, 2-DCP, the number of microbubbles in liver cells and the infiltration of inflammatory cells increased gradually. No pathological changes were found in the gallbladder. Compared with the blank group and solvent control group, the content of serum ALT in each exposure group was increased, the serum levels of IL-6 and TNF-ß in 860, 1150, 1950 and 2350 mg/kg exposure groups were increased, the serum TNF-α and TBLI levels in 1 950, 2535 mg/kg groups were significantly higher (P<0.05) . The levels of ALT, TBLI and TNF-ß in serum of female mice were significantly different (P<0.05) . There were significant differences in ALT, TBLI, CRP, IL-6, TNF-α, TNF-ß in serum of male mice (P<0.05) . Conclusion: Oral 1, 2-DCP may cause acute liver injury in BALB/cA-nu mice and increase the expression of serum inflammatory factors. Moreover, the types of inflammatory factors activated in male mice are more than those in female mice.

[Evaluating the level of occupational stress and its influence factors among traffic police in a district in Shanghai].

Objective: To investigate the high occupational stress and its influencing factors in traffic police in Shanghai. Methods: 728 traffic police were selected as the study subjects, and the《Occupational Health Questionnaire》was used to investigate and evaluate their job demand-control (JDC) and effort-reward imbalance model (ERI) occupational stress situation respectively. The related influencing factors were analyzed. Results: The prevalence rates of high occupational stress in JDC and ERI models were 74.6% (543/728) and 51.5% (375/728) . The influencing factors of JDC were education, marriage, average weekly hours (χ(2)=16.82, 10.04, 18.71, P<0.05) , and The influencing factors of ERI were gender, age, marriage, real monthly income level, education, work experience, and average weekly hours (χ(2)=7.02, 26.18, 6.73, 50.42, 4.75, 26.61, 112.98, 6.19, P<0.05) . The JDC multivariate logistic analysis indicated that the risk of occupational stress of married police was 2.81 times as high as that of Unmarried ones. The risk of occupational stress of traffic police with more education was 1.92 times as high as that of low eduacation, average weekly working 41-50 hours and≥51 hours was 2.53, 3.12 times as high as that of ones with average working 40 hours, respectivly. Meanwhile, the ERI multivariate logistic analysis indicated that high income level is the protective factor of occupational stress. The traffic police with 15-<20 working years were more likely to occur higher occupational stress. The traffic police with the more average weekly hours had greater possibility of higher occupational stress. Conclusion: The main influencing factors of JDC and ERI are marriage, real monthly income level, education, work experience, and average weekly hours.

[Clinical cohort study of imaging evaluation and postoperative pathology of carotid vulnerable plaque].

Objective: To evaluate the accuracy of contrast-enhanced ultrasound(CEUS) scanning in identifying vulnerable plaque in carotid artery. Methods: The study included a total of 25 patients who suffered from carotid artery stenosis and underwent carotid endarterectomy from January 2016 to December 2017 in Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University. Preoperative carotid artery contrast enhanced ultrasound and High-resolution MRI were performed to all patients to determine whether the plaques were stable. All patients then underwent carotid endarterectomy, during which, plaques were completely removed. Biopsies were performed using HE staining and CD31, CD34 and SMA immunohistochemistry was used to identify the plaques properties, including the thickness and integrity of the fiber cap, neovascular endothelium, hemorrhage, and inflammatory cells in the removed plaques.The results of these tests were compared with the diagnosis through the pre-operative imaging. Results: Among twenty-five cases, the pre-operative CEUS revealed sixteen with unstable plaques and nine with stable plaques. Meanwhile the post-operation pathology confirmed seventeen cases with unstable plaque components. The sensitivity of CEUS in the identification of carotid vulnerable plaque was 88.2%(15/17), the specificity was 87.5%(7/8), and the overall diagnostic accuracy was 88%(22/25). The sensitivity, specificity and overall diagnostic accuracy of high resolution MR for vulnerable plaque identification were 83.3%(10/12), 71.4%(5/7), 78.9%(15/19), respectively. There were no significant difference between two groups(χ(2)=0.003, P>0.05). Conclusions: The sensitivity, specificity and overall diagnostic accuracy of the CEUS for vulnerable plaque identification are high.Therefore, CEUS is recommended as one of the pre-operative diagnostic method for unstable plaque in carotid stenosis.

Preparation and characterization of poly(lactic acid) nanoparticles for sustained release of pyridostigmine bromide.

A novel pyridostigmine bromide poly (lactic acid) nanoparticles (PBPNPs) was prepared to obtain sustained release characteristics of PB. A central composite design approach was employed for process optimization. The in vitro release studies were carried out by dialysis method and conducted using four different dissolution media. Similar factor method was investigated for dissolution profile comparison. Multiple linear regression analysis for process optimization revealed that the optimal PBPNPs were obtained where the values of the amount of PB (X1, mg), PLA concentration (X2, % w:v), and PVA concentration (X3, % w:v) were 49.20 mg, 3.31% and 3.41%, respectively. The average particle size and zeta potential of PBPNPs with the optimized formulation were 722.9 +/- 4.3 nm, and -25.12 +/- 1.2 mV, respectively. PBPNPs provided an initial burst of drug release followed by a very slow release over an extended period of time (72 h). Compared with free PB, PBPNPs had a significantly lower release rate of PB in vitro. The in vitro release profile of the PBPNPs could be described by Weibull models, regardless of type of dissolution medium. Statistical significance of similarity between every two dissolution profiles of PBPNPs in different dissolution media was found, and the difference between the curves of PBPNPs and pure PB was statistically significant.

Circ_0032627 accelerates proliferation of gastric cancer cells through regulating miR-502-5p expression.

OBJECTIVE: To explore the biological functions of circ_0032627 in the progression of gastric cancer (GC). MATERIALS AND METHODS: The expression level of circ_0032627 in GC cell lines and gastric mucosal cell lines was measured via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, and FACS were performed to examine the influences of circ_0032627 on the proliferation and apoptosis of GC cells. The relationship between circ_0032627 and micro ribonucleic acids (miRNAs) was predicted on-line using StarBase software, and whether circ_0032627 can act as the sponge of the selected miRNAs was verified via Dual-Luciferase reporter assay and qRT-PCR. Finally, MTT assay was conducted to detect the influences of the co-knockdown of circ_0032627 and the selected miRNAs on the proliferation of GC cells. RESULTS: Compared with that in gastric mucosal cell lines, the expression level of circ_0032627 was upregulated in the selected four GC cell lines, and circ_0032627 knockdown substantially inhibited the proliferation of GC cells, but promoted their apoptosis. Circ_0032627 could act as a sponge of miR-502-5p, and miR-502-3p knockdown reversed the inhibitory effect of circ_0032627 on the proliferation of GC cells. CONCLUSIONS: The expression level of circ_0032627 is raised in GC cells, and circ_0032627 affects the proliferation and apoptosis of GC cells by sponging miR-502-5p.

Primary natural killer/T-cell lymphomas of the oral cavity are aggressive neoplasms.

Thirty-four cases of primary non-Hodgkin's lymphoma of the oral cavity were investigated for their clinical findings, histopathological features, immunophenotypes and association with Epstein-Barr virus (EBV). Four cases (12%) were natural killer/T-cell lymphomas, 3 (9%) were T-cell lymphomas and 27 (79%) were B-cell lymphomas. Compared with T- and B-cell lymphomas, NK/T-cell lymphomas had a male predominance (M:F 4:0), and most presented as ulceration of the palate and/or maxillary gingiva. Histologically, the lesions showed diffuse infiltration of medium-sized or large lymphoid tumour cells. Angiocentricity and/or angioinvasion were found in all 4 cases. The immunophenotypes of the NK/T-cell lymphomas were CD3+, CD43+, CD45RO+, CD56+ and TIA-1+. EBV was detected in 2 NK/T-cell lymphomas by in situ hybridization (ISH) and polymerase chain reaction (PCR) methods, and was not detected in T- and B-cell lymphomas. The survival rate of patients with NK/T-cell lymphoma was zero, but the survival rates for patients with T-cell and B-cell lymphomas were 67% and 38%, respectively. It appears that NK/T-cell lymphomas of the oral cavity have a predilection for originating in the palate and maxillary gingiva and are aggressive neoplasms. EBV positivity might be associated with more aggressive behaviour.

[The clinicopathologic study of histiocytic necrotizing lymphadenitis and the differentiated diagnosis with malignant lymphoma--report of 31 cases].

Histiocytic necrotizing lymphadenitis (HNL) is a kind of rare benign disease, predilection to involve the neck of young women, causing enlargement of the lymph nodes and usually accompanying by fever and other constitutional symptoms, and a unique clinicopathologic course are characteristic of this disease. Because its histomorphology has a given spectrum changing, it may lead to misdiagnosis for someone who is unfamiliar with it. According to the document records, misdiagnostis of HNL could be up to 30%-40%, especially in its early proliferative stage. In this 31 cases analysis, the authors systematically summarize the clinicopathologic characteristics of this lesion, and focus to elucidate the different features between HNL and lymphoma. Although presently it is thought that the disease is self-limited, there are two cases with clinical manifestations of systemic lupus erythematosus in our series. Possibly, the two diseases may have some intrinsic relationships. Long term follow-up of its final outcome in these patients is necessary to clarify whether or not HNL is a self-limiting or progressive disease.

[Clinical significance of congenital fusion of cervical vertebrae: a report of 87 cases].

Based on clinical analysis of 87 cases with congenital fusion of cervical vertebrae, the clinical significance of these lesions was discussed in detail. It was found that the C 2-3 and then the C 3-4 were the sites of frequent involvement. Fusion of 2 to 3 segments was common and showed no clinical signs of abnormality, nor associated with any other malformations. While fusion of multiple segments, though rare, was often associated with other anomalies such as short neck, lowered posterior hair line, webbed neck and malformation of internal organs and other bones. Single lesion does not give rise to symptoms until late when degenerative changes have taken place in the unfused vertebrae in most cases, or following trauma in occasional patients, usually of neurologic upsets. However, fusion at several especially levels, fusion of C 2-3 with occipitalization of atlas predisposes the nerve to damage. In short, remedy is only necessary for cases with symptoms: conservative treatment for those with symptoms caused by radiculopathy, and operation for those with symptoms of myelopathy.