Easy but Efficient: Facile Approach to Molecule with Theoretically Justified Donor-Acceptor Structure for Effective Photothermal Conversion and Intravenous Photothermal Therapy.

To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof-of-concept, hereby a conventional strategy is presented to prepare donor-acceptor (D-A) structured PTAs through cycloaddition-retroelectrocyclization (CA-RE) reaction, and the resultant PTAs give high PCE upon near-infrared (NIR) irradiation. By joint experimental-theoretical study, these PTAs exhibit prominent D-A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA-TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760-nm LED lamp (1.2 W cm-2). In vitro and in vivo experimental results revealed that DMA-TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA-RE reaction as a convenient approach to obtain twisted D-A structured PTAs for effective PTT and probably promote the progress of cancer therapies.

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy: a case report and literature review.

INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

A Detachable Lens-Induced Myopia Model in Mice Based on Clasp Design / 中山大学学报(医学科学版)

ObjectiveTo explore a new model for lens-induced myopia （LIM） in mice and describe the changes of diopter and ocular biological parameters. MethodsTwenty-seven 21-day-old C57BL/6 mice were divided into three groups （ratio， 5：1：3）： LIM group， plano lens （PL） group and normal control （N） group. The right eyes were intervened while the left eyes were left as control. The refraction was detected with retinoscopy after the pupils were dilated with compound topicamide and ocular axial length was measured by optical coherence tomography （OCT） in vivo at baseline and 1， 2， 3， and 4 weeks after the intervention. Paired t test was performed between left and right eyes within each group. Welch's ANOVA was used for comparison among the three groups. When the difference was statistically significant， the Dunnett's T3 was used to correct P value for pairwise comparison. ResultsAfter 2 weeks of defocus induction， the refraction of the intervened eye in LIM group shifted to myopia about （-2.55±1.54） D（t=6.430， P＜0.000 1）， and the ocular axial length （AL） increased about （0.051±0.024） mm（t=7.837， P＜0.000 1）. The difference of interocular change in refraction in LIM group compared with PL group and N group was -2.30 D （P=0.014） and -2.55 D （P＜0.000 1）， respectively. The difference of interocular change in AL in LIM group was 0.048 mm （P<0.000 1） and 0.047 mm （P<0.000 1） compared with that in PL group and N group， respectively. With the extension of intervention time， the degree of myopia drift increased. ConclusionIn this study， a clasp-based and detachable LIM model was described and validated. After 2 weeks of intervention， the refraction shifted significantly toward myopia and the AL increased significantly. The LIM model is simple to construct and can provide a reference for the model construction of animal experiments in myopia research.

CD301b+ macrophage: the new booster for activating bone regeneration in periodontitis treatment / 国际口腔科学杂志·英文版

Periodontal bone regeneration is a major challenge in the treatment of periodontitis. Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed by inflammation, via conventional treatment. CD301b+ macrophages were recently identified as a subpopulation that is characteristic of a regenerative environment, but their role in periodontal bone repair has not been reported. The current study indicates that CD301b+ macrophages may be a constituent component of periodontal bone repair, and that they are devoted to bone formation in the resolving phase of periodontitis. Transcriptome sequencing suggested that CD301b+ macrophages could positively regulate osteogenesis-related processes. In vitro, CD301b+ macrophages could be induced by interleukin 4 (IL-4) unless proinflammatory cytokines such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were present. Mechanistically, CD301b+ macrophages promoted osteoblast differentiation via insulin-like growth factor 1 (IGF-1)/thymoma viral proto-oncogene 1 (Akt)/mammalian target of rapamycin (mTOR) signaling. An osteogenic inducible nano-capsule (OINC) consisting of a gold nanocage loaded with IL-4 as the "core" and mouse neutrophil membrane as the "shell" was designed. When injected into periodontal tissue, OINCs first absorbed proinflammatory cytokines in inflamed periodontal tissue, then released IL-4 controlled by far-red irradiation. These events collectively promoted CD301b+ macrophage enrichment, which further boosted periodontal bone regeneration. The current study highlights the osteoinductive role of CD301b+ macrophages, and suggests a CD301b+ macrophage-targeted induction strategy based on biomimetic nano-capsules for improved therapeutic efficacy, which may also provide a potential therapeutic target and strategy for other inflammatory bone diseases.

Inhibitory Effects and Mechanisms of Three Benzodiazepines on Helicobacter pylori / 中国医学科学院学报

Objective To explore the inhibitory effects and mechanisms of benzodiazepines on Helicobacter pylori (Hp).Methods The Hp international standard strain ATCC43504 was treated with benzodiazepines diazepam,midazolam,and remimazolam,respectively.The treatments with amoxicillin and clarithromycin were taken as the positive controls,and that with water for injection as the negative control.The inhibition zone of each drug was measured by the disk diffusion method.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of each drug against Hp were determined.Hp suspension was configured and treated with diazepam and midazolam,respectively.The bacterial suspension without drug added was used as the control group.The concentration of K+ in each bacterial suspension was measured by an automatic biochemical analyzer before drug intervention(T0)and 1(T1),2(T2),3(T3),4(T4),5(T5),6(T6),and 7 h(T7)after intervention.Hp urease was extracted and treated with 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,2 MIC midazolam,1 mg/ml acetohydroxamic acid,and water for injection,respectively.The time required for the rise from pH 6.8 to pH 7.7 in each group was determined by the phenol red coloring method.Results The inhibition zones of diazepam,midazolam,remimazolam,amoxicillin,clarithromycin,and water for injection against Hp were 52.3,42.7,6.0,72.3,60.8,and 6.0 mm,respectively.Diazepam and midazolam showed the MIC of 12.5 μg/ml and 25.0 μg/ml and the MBC of 25 μg/ml and 50 μg/ml,respectively,to Hp.The concentrations of K+ in the diazepam,midazolam,and control groups increased during T1-T7 compared with those at T0(all P<0.01).The concentration of K+ in diazepam and midazolam groups during T1-T4 was higher than that in the control group(all P<0.01).The time of inhibiting urease activity in the 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,and 2 MIC midazolam groups was(39.86±5.11),(36.52±6.65),(38.58±4.83),(39.25±6.19),(36.36±4.61),and(35.81±6.18)min,respectively,which were shorter than that in the acetohydroxamic acid group(all P<0.01)and had no significance differences from that in the water for injection group(all P>0.05).Conclusion Diazepam and midazolam exerted inhibitory effects on Hp,which may be related to the cleavage of Hp cells rather than inhibiting urease.

Study on the predictive significance of PLR, SII and RPR in ovarian endometriotic cyst / 中华妇产科杂志

Objective: To investigate the predictive value of platelet-to-lymphocyte ratio (PLR), red blood cell distribution width to platelet count ratio (RPR) and systemic immune inflammation index (SII) in the staging and postoperative recurrence of ovarian endometrial cysts. Methods: Retrospective analysis was made on the clinical data of patients who underwent laparoscopic surgery for ovarian cysts in the Affiliated Hospital of Qingdao University from January 2018 to January 2020. The patients with ovarian endometriosis cyst confirmed by pathology after surgery were the observation group (n=350), and the patients with other benign ovarian cyst were the control group (n=150). The preoperative platelet count, platelet distribution width, absolute number of neutrophils, lymphocyte absolute number, absolute number of monocytes, red blood cell distribution width, and serum cancer antigen 125 (CA125) of the patients in two groups were recorded, and PLR, neutrophil-to-lymphocyte ratio (NLR), RPR, SII, and systemic inflammation response index (SIRI) were calculated and analyzed. The general data of all patients and the follow-up data within 2 years after the operation of the observation group were statistically recorded to evaluate the diagnostic value of PLR, RPR and SII for ovarian endometrial cyst, and the predictive value of staging and recurrence within 2 years after the operation. Results: PLR, NLR, SII (median: 147.53, 1.86, and 488.70 respectively) and CA125 (median: 59.41 kU/L) in the observation group were significantly higher than those in the control group, while RPR (median: 0.16) was lower than that in the control group, with significant differences (all P<0.01). There was no significant difference in SIRI between the two groups (P>0.05). The PLR and SII (median: 122.73, 345.00) of the observation group at stage Ⅲ and Ⅳ were higher than those of patients at stage Ⅰ and Ⅱ, and the RPR was lower than that of patients with stage Ⅰ and Ⅱ, with significant differences (all P<0.001). The PLR, NLR, SII, SIRI (median: 179.63, 2.75, 762.96, and 1.06 respectively) and CA125 (median: 108.83 kU/L) in patients with recurrence were significantly higher than those in patients without recurrence 2 years after the operation, and the differences were statistically significant (all P<0.001). The area under curve (AUC) of CA125 in the diagnosis of ovarian endometriosis cyst was 0.951, the sensitivity was 85.7%, and the specificity was 93.0%, which were higher than those of PLR and SII; the AUC of PLR+SII+CA125 in the diagnosis of ovarian endometriosis cyst was 0.952. The AUC of RPR predicting the stage of ovarian endometriosis cyst was 0.713, higher than PLR and SII, lower than CA125; the AUC of RPR+SII+CA125 in predicting the stage of ovarian endometriotic cyst was 0.825, with sensitivity of 68.7% and specificity of 85.7%. The AUC predicted by SII for recurrence of ovarian endometriotic cyst within 2 years after the operation was 0.803, higher than NLR, PLR, SIRI and CA125; the AUC of PLR+SII+CA125, sensitivity, specificity was 0.813, 81.5% and 73.0%, higher than SII. Conclusion: PLR, RPR and SII are related to the staging of ovarian endometriotic cyst, and SII has a certain predictive value for the recurrence of ovarian endometriotic cyst after surgery.

Discovery of a highly potent and orally available importin-β1 inhibitor that overcomes enzalutamide-resistance in advanced prostate cancer

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Role of dendritic cells in MYD88-mediated immune recognition and osteoinduction initiated by the implantation of biomaterials / 国际口腔科学杂志·英文版

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.

Efficacy of micro steel plate and Kirschner needle oblique and transverse internal fixation of adjacent metacarpal bone in the treatment of metacarpal diaphyseal oblique fracture / 中国骨伤

OBJECTIVE@#To compare the clinical efficacy of micro steel plate and Kirschner needle oblique and transverse internal fixation of adjacent metacarpal bone in the treatment of metacarpal diaphyseal oblique fracture.@*METHODS@#Fifty-nine patients with metacarpal diaphyseal oblique fractures admitted between January 2018 and September 2021 were selected as the study subjects and divided into the observation group (29 cases) and the control group (30 cases) based on different internal fixation methods. The observation group was treated with Kirschner wire oblique and transverse internal fixation of adjacent metacarpal bones, while the control group was treated with micro steel plate internal fixation. Postoperative complications, operation time, incision length, fracture healing time, treatment cost, and metacarpophalangeal function were compared between the two groups.@*RESULTS@#No incision or Kirschner wire infections occurred in the 59 patients, except for one in the observation group. No fixation loosening, rupture, or loss of fracture reduction occurred in any of the patients. The operation time and incision length in the observation group were (20.5±4.2) min and (1.6±0.2) cm, respectively, which were significantly shorter than those in the control group (30.8±5.6) min and (4.3±0.8) cm (P<0.05). The treatment cost and fracture healing time in the observation group were (3 804.5±300.8) yuan and (7.2±1.1) weeks, respectively, which were significantly lower than those in the control group (9 906.9±860.6) yuan and (9.3±1.7) weeks (P<0.05). The excellent and good rate of metacarpophalangeal joint function in the observation group was significantly higher than that in the control group at 1, 2, and 3 months after operation (P<0.05), but there was no significant difference between the two groups at 6 months after operation (P>0.05).@*CONCLUSION@#Micro steel plate internal fixation and Kirschner wire oblique and transverse internal fixation of adjacent metacarpal bones are both viable surgical methods for treating metacarpal diaphyseal oblique fractures. However, the latter has the advantages of causing less surgical trauma, shorter operation time, better fracture healing, lower cost of fixation materials, and no need for secondary incision and removal of internal fixation.

Emergency response of infectious snails detected after interruption of schistosomiasis transmission in Hannan District, Wuhan / 中国热带医学

@#Abstract: Objective　To analyze the emergency response and long-term intervention effects after the detection of infectious snails epidemic by loop-mediated isothermal amplification (LAMP) assays in Hannan District, Wuhan City, and to explore the application of LAMP in early surveillance and early-warning of schistosomiasis transmission. Methods Snails picked up by the risk monitoring system in Hannan District were examined by anatomical microscopy and LAMP technology to identify the schistosomiasis infection. Emergency response and intensive intervention were initiated in the environment where positive snails appeared, and the long-term effects were evaluated. Results In May 2018, the infectious snails were detected by LAMP technology in Hannan District, and the positive snails were located in Zhujiacha, Dongzhuang Village, Obstacles and weeds were removed and buried by machine in Zhujiacha. 12 700 m2 of snails were killed by drugs, and the mortality rate of snails was more than 80%; no new seropositive persons were found in the emergency examination within 500 m of the positive snail sites. 506 people were examined in Dong Zhuang Village at the end of the year, and 30 positive IHA cases were detected with a blood positive rate of 5.93%, no positive fecal test was found, and all positive blood test patients took preventive medication. The monitoring results of sentinel rats and wild feces were all negative. Health education was carried out, 7 warning signs were deployed and refreshed, and 500 publicity brochures were distributed. After nearly three years of intensified intervention and monitoring in the villages where the positive environment is located, and the density of snails on the stubborn snail has dropped from 0.094/frame to 0.027/frame, and the positive rate of blood test in Dongzhuang Village has steadily dropped from 5.93% to 3.74%. Conclusions The infected snails missed by microscopy were detected by LAMP in Hannan District, which created conditions for the rapid emergency treatment of environment and elimination of positive snail and improved the sensitivity of the surveillance and early warning system in transmission-interrupted areas.

Three-dimensional finite element study on the effects of maxillary anterior two-step retraction and en-masse retraction with clear aligners / 中华口腔医学杂志

Objective: To investigate the effects of two-step retraction and en-masse retraction on tooth movement pattern of anterior teeth and posterior anchorage with clear aligners using three-dimensional finite element analysis. Methods: A finite element model of maxillary first premolar extraction case undergoing clear aligner treatment was established based on maxillofacial cone-beam CT data of a 24-year-old adult male with individual normal occlusion, who visited Department of Oral Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine for impacted mandibular third molar in June, 2022. The initial tooth displacement of five anterior retraction protocols (two-step with canine retraction, two-step with incisor bodily retraction, two-step with incisor retraction-overtreatment, en-masse bodily retraction, and en-masse retraction-overtreatment) were evaluated. Results: Two step with canine retraction caused distal tipping of the canine and labial tipping of the incisors (0.18° for central incisor and 0.13° for lateral incisor). Two step with incisor retraction caused mesial tipping of the canine. In two step with bodily retraction protocol, uncontrolled lingual tipping was found in central incisor (0.29°) and lateral incisor (0.32°). In two-step with incisor retraction-overtreatment protocol, the movement pattern of the incisors didn't change, but the inclinations reduced to 0.21° and 0.18°. En-masse retraction caused distal tipping of the canine. In en-masse bodily retraction protocol, uncontrolled lingual tipping was also found in central incisor (0.19°) and lateral incisor (0.27°). In en-masse retraction-overtreatment protocol, the central incisor showed controlled lingual tipping (0.02°) and the lateral incisor showed palatal root movement (0.03° labial inclination). Posterior teeth exhibited mesial tipping in all five protocols. Conclusion: En-masse retraction with incisor overtreatment was beneficial to incisor torque control in clear aligner treatment.

Heparin-binding hemagglutinin as a composition antigen of tuberculosis vaccine exerts protective immune effects by inducing IL-17 / 中华预防医学杂志

To explore the protective immune effect induced by mucosal delivery heparin-binding hemagglutinin (HBHA)-a candidate vaccine antigen of Mycobacterium tuberculosis. Female C57BL/6 mice were between 6 and 8 weeks of age before experimental use. Thirty mice received different immunization strategies and were randomly divided into the control group, the early secreting antigen target-6 (ESAT-6) intranasal immunization group, the HBHA intranasal immunization group, the BCG priming PBS control group, or BCG priming HBHA boost group, 6 mice in each group. In order to analyzed the immune effect, the concentrations of plasma Interleukin-17A (IL-17A) and other cytokines were measured by ELISA. Quantitative real-time PCR analyses were performed to detect the relative quantity (RQ) mRNA of IL-17A in the lung. The lung tissue sections were stained to detect the formation of the tertiary lymphoid structures. The chemokines contributed to formation of the tertiary lymphoid structures were also measured. Flow cytometry was used to detect the frequency of Th1 and Th17 cells in the system. Sixty mice in the BCG priming PBS control group and the BCG priming HBHA boost group were sacrificed at different time points after infection to count the lung bacterial burden. The concentrations of plasma IL-17A and relative quantity of lung IL-17A mRNA were highest in the BCG priming HBHA boost group [(14.76±4.73) pg/mL,RQ (12.27±6.71)], which was significantly higher than the control group [(5.57±2.95) pg/mL,RQ (1.30±0.97)] (t=4.213, P<0.001; t=5.984, P<0.001), and also significantly higher than the BCG priming PBS control group [(6.81±2.18) pg/mL,RQ (1.44±1.16)] (t=3.646 P=0.001; t=6.185 P<0.001). Compared with the BCG priming PBS control group (0.38±0.38)% the frequency of spleen Th17 cells were also significantly increased (t=-0.280 , P=0.048) in the BCG-primary HBHA boost group (1.02±0.34)%. In addition, HBHA boosting could promote better formation of the tertiary lymphoid structures in the lung, and decrease the bacterial load on the early stage after BCG challenge. Collectively, mucosal delivery of HBHA can effectively enhance the protective effect after BCG vaccination, and it is a potential candidate vaccine component.

Chemokine receptor CX3CR1 promotes local remodeling of monocyte-derived Langerhans cell subsets to maintain chronic skin inflammation / 中华微生物学和免疫学杂志

Objective:To investigate the role of chemokine receptor CX3CR1 in chronic skin inflammation and its regulatory mechanism.Methods:Wild type (WT) C57BL/6 mice and Cx3 cr1 GFP/GFP mice were induced by DNFB to establish acute and chronic allergic contact dermatitis (ACD) model. Ear inflammation and swelling were observed with hematoxylin-eosin (HE) staining. Flow cytometry (FCM) was used to detect the changes in classical Langerhans cell (LC) and monocyte-derived LC (Mo-LC), as well as the expression of major histocompatibility complex Ⅱ (MHCⅡ), inducible nitric oxide synthase (iNOS) and TNF-α. Changes in epidermal LC in UV irradiation-induced dermatitis models were also analyzed. In human chronic skin inflammation, CX3CL1 expression was detected using immunohistochemistry, RT-PCR and Western blot and CD1a, CD14 and CD207 expression was observed with immunofluorescence staining. Results:In the chronic ACD model, Cx3 cr1 GFP/GFP mice showed significantly alleviated ear inflammatory and swelling as compared with WT mice, but no significant difference was found in the acute ACD model. The percentages of Mo-LC were decreased in the chronic ACD model and after three weeks of UV irradiation. Moreover, MHCⅡ, TNF-α and iNOS expressed by Mo-LC were significantly upregulated as compared with those by classical LC. CX3CL1 expression was significantly upregulated and the numbers of CD14 + monocytes and CD1a + langerin - Mo-LC were dramatically increased in human chronic skin inflammation. Conclusions:CX3CR1 might maintain inflammatory response by regulating local remodeling of Mo-LC in chronic skin inflammation.

Analysis of inflammatory characteristics and changes of small airway function in patients with eosinophil and neutrophil asthma / 中国综合临床

Obsjective To analyze the inflammation characteristics and changes of small airway function in patients with eosinophil and neutrophil asthma, and provide evidence for individualized treatment of asthma. Methods:Using a cross-sectional study, 46 patients with eosinophilic asthma and 42 patients with neutrophilic asthma confirmed by cytology of induced sputum were recruited from July 1, 2017 to June 30, 2019 at the respiratory Department of Respiratory Medicine,Jinshan Branch of the Sixth People's Hospital of Shanghai. Patients were divided by asthma category into eosinophilic asthma group and neutrophilic asthma group.The severity of acute attack, the score of asthma control test (ACT) and the concentration of serum C-reactive protein (CRP) were compared between the two groups The fraction of exhaled nitric oxide (FeNO), related cytokines(interleukin-4(IL-4), interleukin-5(IL-5), interleukin-13(IL-13), interleukin-17(IL-17) and interferon γ(IFN-γ)) in peripheral blood and induced sputum supernatant and lung function indicators (forced exhalation volume in one second (FEV1)% percent predicted (%pred), maximal mid-expiratory flow (MMEF)% pred, forced expiratory flow (FEF) 75% pred, forced expiratory flow at 50% of FVC exhaled (FEF50%) pred were detected. Independent sample t-test was used for the comparison between measurement data groups comforming to normal distritution, rank sum test was used for the comparison between measurement data groups not conforming to normal distribution, and χ 2 test was used for the comparison of counting data. Results:There were no significant differences in the general data and ACT scores between the two groups (all P>0.05). The ratio of severe and critical degree (52.38%(22/42)), uncontrolled and partially controlled patients (59.52%(25/42)), CRP level (24.6(7.1, 35.0) mg/L) in neutrophil asthma group were higher than those in eosinophilic asthma group(30.43% (14/46), 36.96% (17/46), and 8.5 (2.0, 12.0) mg/L, respectively) (χ 2=4.37, χ 2=4.48, Z=4.76; P=0.036, P=0.034, P<0.001). The concentration of FeNO was higher in eosinophilic asthma group (76(54,93) ppb) than that in neutrophil asthma group(27(15,41) ppb),and the differences was statistically significant ( Z=6.52, P<0.001). The values of FEV1% pred ((56.13±21.51)%), MMEF% pred ((62.03±23.97)%), FEF75% pred ((54.42±20.49)%), FEF50% pred ((66.89±26.47)%) in neutrophil asthma group were lower than those in eosinophilic asthma group ((68.53±29.81)%, (72.16±23.05)%, (65.38±25.46)% and (79.86±27.61)%), and the difference between the two groups was statistically significant( t values were 2.25, 2.02, 2.21, 2.24; P values were 0.027, 0.046, 0.030, 0.027). The concentrations of serum IL-4((49.42±24.46) ng/L), IL-5((104.89±43.91) ng/L) and IL-4((44.49±19.12) ng/L), IL-5((95.45±28.58) ng/L) in induced sputum supernatant were higher than neutrophilic asthma group((32.29±14.19), (50.35±22.30), (33.33±15.08), (55.61±26.41) ng/L). The difference between the two groups was statistically significant ( t values were 4.06, 7.44, 3.02, 6.77, P values were <0.001, <0.001, 0.003, <0.001). In eosinophilic asthma group, the concentrations of serum IL-13 ((76.18±20.62) ng/L), IL-17 ((31.32±9.32) ng/L), IFN-γ ((18.27±5.56) ng/L) and IL-13((71.08±20.08) ng/L), IL-17((26.29±6.70) ng/L), and IFN-γ((17.61±5.94) ng/L) in induced sputum supernatant were lower than those in neutrophilic asthma group((153.83±44.53 ) ng/L, (55.27±18.89) ng/L, (26.46±10.08) ng/L, (120.32±28.41) ng/L, (44.99±12.66) ng/L, (23.91±7.66) ng/L). The difference between the two groups was statistically significant ( t values were 10.33, 7.43, 4.66,9.31,8.54,4.33, respectively; all P<0.001). Conclusion:Eosinophilic asthma and neutrophil asthma have different inflammation, small airway function characteristics and different response to treatment. The small airway function changes in early stage of neutrophil asthma are more obvious.

Controlled release and cytobiology of recombinant human parathyroid hormone 1-34 mediated by hyaluronic acid thermo-sensitive hydrogels / 药学学报

The bone formation promoter recombinant human parathyroid hormone 1-34 [PTH (1-34)] has a short half-life and low bioavailability. In this study, we prepared a biodegradable and temperature-sensitive hyaluronic acid-poly-N-isopropyl acrylamide (AHA-g-PNIPAAm), and further investigated its effects of PTH (1-34) release and cell behavior as drug carrier. The structure of AHA-g-PNIPAAM was confirmed by hydrogen nuclear magnetic resonance spectroscopy and infrared spectroscopy. Next, PTH (1-34) loaded thermo-sensitive hydrogels were prepared by physical swelling method and their stability was investigated. The morphology of hydrogel was observed by scanning electron microscope. The minimum critical transition temperature and drug release behavior of hydrogels were investigated by ultraviolet spectrophotometry. The tetrazolium-based colorimetric assay (MTT assay) was used to investigate the toxicity and proliferation effects of PTH (1-34)-loaded thermo-sensitive hydrogel on mouse mononuclear macrophage RAW264.7 and mouse precranial osteoblasts MC3T3-E1. The effect of PTH (1-34)-loaded thermo-sensitive hydrogel on the differentiation of RAW264.7 was investigated by the tartrate-resistant acid phosphatase assay. The results showed that the PTH (1-34)-loaded thermo-sensitive hydrogel prepared in this study displayed regular three-dimensional honeycomb structure, and had good stability, thermo-sensitivity and sustained and controlled release properties, which could promote the proliferation of MC3T3-E1 cells more effectively and inhibit the differentiation of RAW264.7 into osteoclasts.

NAT10 Promotes Cervical Cancer Cell Malignant Behavior via N4-acetylcytidine Modification of DDR1 mRNA / 中国生物化学与分子生物学报

N-acetyltransferase 10 (NAT10) is a key enzyme involved in the acetylation of mRNA, which regulates the expression of target genes and biological functions of various cancers via ac4C (N4-acetylcytidine) acetylation. However, whether NAT10 is involved in regulating the malignant behavior of cervical cancer is rarely reported. This study investigated the effects and specific mechanism of NAT10 on the growth activity, proliferation capacity, migration and invasion capacity of cervical cancer cells. First, we found a highly expression of NAT10 in cervical cancer and was associated with poor patient prognosis by TCGA database analysis. MTT assays and colony formation assays showed that overexpression of NAT10 promoted the growth activity (P<0. 05) and proliferation ability (P<0. 001) of cervical cancer cells; Transwell migration and invasion assays showed that overexpression of NAT10 promoted the migration (P<0. 01) and invasion (P<0. 05) ability of cervical cancer cells; Western blotting showed that overexpression of NAT10 increased the mesothelial cell marker vimentin and resulted in a decrease in the epithelial cell marker E-cadherin. Bioinformatics analysis exhibited that discoidin domain receptor 1 (DDR1) might be a downstream target gene of NAT10. RNA binding protein immunoprecipitation (RIP) assays showed that NAT10 could directly bind to DDR1 mRNA (P<0. 05), Western blotting and RT-qPCR experiments showed that overexpression of NAT10 significantly increased the expression and mRNA levels of DDR1 (P<0. 05). Furthermore, RNA acetylation co-immunoprecipitation experiments showed that overexpression of NAT10 promoted the acetylation level of DDR1 mRNA (P<0. 001), and EGFP reporter assays confirmed that NAT10 recognized the acetylation site of DDR1 mRNA. The results of mRNA half-life experiments showed that NAT10 increased the stability of DDR1 mRNA (P<0. 05). In conclusion, our research confirms that NAT10 promotes the growth activity, and migration and invasion ability of cervical cancer cells and its specific mechanism is to extend the stability of DDR1 by acetylation modification, thereby increasing its expression levels, which might provide new insights into the molecular mechanism of acetylation modification of mRNA on the pathogenesis of cervical cancers.

MicroRNA-124-5p delays the progression of cerebral aneurysm by regulating FoxO1.

Cerebral aneurysm (CA) is a common brain disease, and the development of cerebral aneurysm is driven by inflammation and hemodynamic stress. MicroRNA (miR)-124-5p is reported to be associated with inflammatory response in brain disease such as cerebral ischemia-reperfusion injury. However, the function and molecular mechanism of miR-124-5p in CA are not clear, thus, the effects of miR-124-5p on inflammatory response in CA were explored. Firstly, the expression of miR-124-5p in the peripheral blood of patients with CA and the control group was detected by reverse transcription-quantitative PCR. Then, the human umbilical vein endothelial cells (HUVECs) were used as an in vitro model system and stimulated with interleukin (IL)-1ß to simulate the inflammatory environment of CA, and the expression of miR-124-5p was detected. Next, the effect of miR-124-5p on the migration and invasion of HUVECs was detected using Transwell assays. Meanwhile, the function of miR-124-5p on various inflammatory factors was determined by western blotting and enzyme-linked immunosorbent assay (ELISA). Next, the TargetScan website was used to predict FoxO1 as a target gene of miR-124-5p, and this target association was validated by double luciferase reporter assay and western blotting. Finally, the interaction of miR-124-5p with FoxO1 in CA was measured by Transwell western blotting and ELISA assays. The results showed that the expression level of miR-124-5p in the peripheral blood of patients with CA was lower compared with that of control group, and the miR-124-5p in HUVECs stimulated by IL-1ß was less compared with that in normal HUVECs. Besides, miR-124-5p could inhibit the migration and invasion abilities of HUVECs and the release of inflammatory factors. Additionally, the overexpression of miR-124-5p was able to inhibit the expression of FoxO1. miR-124-5p-inhibitor promoted the migration and invasion of HUVECs, as well as inflammatory response, which was weakened following the introduction of FoxO1 small interfering RNA. Overall, the present study demonstrated that miR-124-5p could prevent the occurrence and development of cerebral aneurysm by downregulating the expression of FoxO1.

Weak value amplification for angular velocity measurements.

The weak-value-amplification technique has shown great importance in the measurement of tiny physical effects. Here we introduce a polarization-dependent angular velocity measurement system consisting of two Glan prisms and a true zero-order half-wave plate, where a non-Fourier-limited Gaussian pulse acts as the meter. The angular velocities measurements results agree well with theoretical predictions, and its uncertainties are bounded by the Cramér-Rao bound. We also investigate uncertainties of angular velocities for different numbers of detected photons and the smallest reliable postselection probability, which can reach ${3.42*10^{- 6}}$.

Ablation Therapy Combined with EGFR TKIs in the Treatment of Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Systematically evaluate the efficacy of physical ablation combined with TKI in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: We performed a comprehensive search of databases including OVID, PubMed, EMBASE, the Cochrane Library, and three Chinese databases (China National Knowledge Infrastructure, Wanfang Database, and Chongqing Weipu Database). The aim was to identify randomized controlled trials (RCT) investigating physical ablation as the treatment for advanced NSCLC. We also evaluated the methodological quality of the included studies and summarized the data extracted for meta-analysis with Review Manager 5.3. RESULTS: A total of 9 studies, including 752 patients, were evaluable. The meta-analysis results show that the complete response rate (CRR) (RR: 2.23, 95% CI: 1. 46 to 3.40, P 0.01), partial response rate (PRR) (RR: -2.25, 95% CI: 1.41 to 3.59, P 0.01), and disease control rate (DCR) (RR: -2.80, 95% CI: 1.64 to 4.80, P< 0.01) of patients with advanced NSCLC who received physical ablation combined with TKI therapy were higher than those who did not receive physical ablation therapy. The control groups from seven of the studies had a total of 606 patients with targeted therapies and chemotherapy. The complete response rate was (CRR) (RR: 2.48, 2.4895% CI: 1.55 to 2.47, P 0.01), partial response rate (PRR) (RR: -1.66, 95% CI: 1.20 to 2.31, P< 0.01), and disease control rate (DCR) (RR: -2.68, 95% CI: 1.41 to 5.06, P< 0.01) for patients with advanced NSCLC who had received physical ablation combined with targeted therapies and chemotherapy, compared to patients who had not received physical ablation therapy. This difference was statistically significant. Above all, these results showed that the clinical efficacy of physical ablation combined EGFR-TKIs therapy (regardless of whether it was combined with chemotherapy) was better than that of EGFR-TKIs therapy alone. CONCLUSION: Physical ablation combined with TKI treatment in patients with advanced NSCLC can improve efficacy.

Short-term follow-up results of inflatable mediastinoscopy combined with laparoscopy versus video-assisted thoracoscopic surgery combined with laparoscopy for esophageal cancer / 中国胸心血管外科临床杂志

@#Objective    To investigate the short-term follow-up results of inflatable mediastinoscopy combined with laparoscopy in the treatment of esophageal cancer. Methods    Clinical data of 102 patients with esophageal cancer who underwent minimally invasive esophagectomy were enrolled in our hospital from January 2017 to January 2019. Patients were divided into two groups according to different surgical methods, including a single-port inflatable mediastinoscopy combined with laparoscopy group (group A, n=59, 53 males and 6 females, aged 63.3±7.6 years, ranging from 45 to 75 years) and a video-assisted thoracoscopy combined with laparoscopy group (group B, n=43, 35 males and 8 females, aged 66.7±6.7 years, ranging from 50-82 years). The short-term follow-up results of the two groups were compared. Results    Compared with the group A, the rate of postoperative pulmonary complication of the group B was significantly lower (18.64% vs. 4.65%, P<0.05). There was no significant difference between the two groups in other postoperative complications (P>0.05). The 6-month, 1-year, and 2-year survival rates were 96.61%, 89.83%, and 73.33%, respectively in the group A, and were 95.35%, 93.02%, and 79.17%, respectively in the group B. There was no significant difference in short-term survival rate after operation (P>0.05). Conclusion    In the treatment of esophageal cancer, the incidence of pulmonary complications of inflatable mediastinoscopy combined with laparoscopy is lower than that of traditional video-assisted thoracoscopy combined with laparoscopy, and there is no significant difference in other postoperative complications or short-term survival rate between the two methods. Inflatable mediastinoscopy combined with laparoscopy for radical esophageal cancer is a relatively safe surgical method with good short-term curative effects, and long-term curative effects need to be further tested.