Objective:To identify and characterize one Yokenella regensburgei strain(designated as CXLZQ123) isolated from a case of perionychial abscess. Methods:Strain CXLZQ123 was isolated from a patient with periungual abscess at the Dermatology Department of San County Central Hospital in June 2, 2023. The strain was initially identified through morphological and biochemical tests, followed by mass spectrometry identification, 16S rRNA sequencing and whole-genome sequencing. MEGA 11.0 was used to compare and analyze the strain′s genetic relationship with relevant species in GenBank, and a phylogenetic tree was constructed based on genetic distance to analyze its genetic evolution. Meanwhile, the average nucleotide identity between its genome and similar strains were compared.Results:The strain was identified as a Gram-negative rod. MicroScan WalkAway biochemical tests indicated that the strain was either Yokenella regensburgei (91.47%) or Hafnia alvei (8.53%). MALDI-TOF mass spectrometry confirmed it as Yokenella regensburgei. Based on 16S rRNA gene sequence analysis, the strain showed the highest similarity(99.37%) to CIP 105435 (sequence number NR_104934.1). The 16S rRNA gene sequence of the isolated strain Yokenella regensburgei was submitted to the National Center for Biotechnology Information (NCBI) with the GenBank sequence number of OR230248.1. The whole-genome of CXLZQ123 were sequenced and uploaded (NCBI, SRA sequence number: SRR26510420). The average nucleotide identity between CXLZQ123 and Yokenella regensburgei strains W13 and UU2206353 were 98.82% and 99.04%, respectively. Conclusions:Through morphological observation, biochemical identification, mass spectrometry identification, 16S rRNA and whole-genome sequencing, this pathogenic strain is identified as Yokenella regensburgei. This rare bacterium is sensitive to most detected antibiotics. This study provides diagnostic and treatment experience for Yokenella regensburgei-related infections.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs (miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34c-5p on cardiac hypertrophy and the mechanism involved. The expression of miR-34c-5p was proved to be elevated in heart tissues from isoprenaline (ISO)-infused mice. ISO also promoted miR-34c-5p level in primary cultures of neonatal rat cardiomyocytes (NRCMs). Transfection with miR-34c-5p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor (Anf) and β-myosin heavy chain (β-Mhc) in NRCMs. In contrast, treatment with miR-34c-5p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34c-5p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34c-5p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34c-5p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4B (ATG4B) was identified as a direct target of miR-34c-5p, and miR-34c-5p was certified to interact with 3' untranslated region of Atg4b mRNA by dual-luciferase reporter assay. miR-34c-5p reduced the expression of ATG4B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34c-5p abolished the detrimental effects of ISO by restoring ATG4B and increasing autophagy. In conclusion, our findings illuminate that miR-34c-5p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4B and autophagy. It suggests that regulation of miR-34c-5p may offer a new way for handling hypertrophy-related cardiac dysfunction.

Objective:To investigate the association between the rehabilitation of visual function and retinal nerve fiber layer (RNFL) thickness in Leber hereditary optic neuropathy (LHON) patients receiving gene therapy for the disease.Methods:A multi-center, non-randomized, single-arm clinical trial was conducted.A total of 159 LHON patients were enrolled in Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Taihe Hospital and Ezhou Central Hospital from December 2017 to December 2018.All of the patients were administered with a single unilateral intravitreal injection (0.05 μl) of recombinant adeno-associated virus 2 carrying reduced nicotinamide adenine dinucleotide dehydrogenase subunit 4 (rAAV2-ND4) and were followed up before and 1, 3, 6 and 12 months after treatment.The best corrected visual acuity (BCVA) converted to logarithm of the minimum angle of resolution (LogMAR) unit was assessed with a standard logarithmic visual acuity chart.Perimetry indicators including visual field index (VFI) and mean deviation (MD) were measured with Humphrey Field Analyzer.RNFL thickness in the superior, inferior, temporal, nasal optic disc and the average RNFL thickness were detected with Spectralis ? HRA+ OCT.The 12-month postoperative BCVA, visual field, and RNFL thickness were taken as the primary outcomes.According to the improvement of BCVA, VFI and MD at 12 months after therapy, there were 81 vision improved eyes with injection, 62 vision unimproved eyes with injection, 65 vision improved eyes without injection, and 78 vision unimproved eyes without injection, 48 VFI improved eyes with injection, 71 VFI unimproved eyes with injection, 47 VFI improved eyes without injection, and 72 VFI unimproved eyes without injection, 52 MD improved eyes with injection, 67 MD unimproved eyes with injection, 47 MD improved eyes without injection, and 72 MD unimproved eyes without injection.The correlations between BCVA, VFI, MD and RNFL thickness were evaluated by Pearson linear correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committees of Wuhan Tongji Hospital (No.TJ-IRB20180316), Taihe Hospital (No.2017-01), Ezhou Central Hospital (No.2017-K-05) and People's Hospital of Wuhan University (No.WDRY2020-K202).Written informed consent was obtained from each patient or custodian prior to entering the study cohort. Results:Among the patients receiving rAAV-ND4 gene therapy, the 12-month postoperative BCVA (LogMAR) in the injected eyes and uninjected eyes was 1.37±0.55 and 1.29±0.59, which were significantly better than 1.70±0.41 and 1.53±0.51 before treatment (baseline), respectively ( t=4.920, 3.550; both at P<0.001).The 12-month postoperative VFI of the patients were significantly improved and the 12-month postoperative MD of the patients were significantly lowered in comparison with those at baseline in the injected eyes (both at P<0.001).Similar improvements of VFI and MD were observed in the uninjected eyes (both at P<0.01).RNFL of the patients was thinner after the therapy.In the vision improved eyes with injection, the BCVA was negatively correlated with superior, inferior, temporal, nasal and average RNFL thickness ( r=-0.362, -0.292, -0.307, -0.308; all at P<0.05).In the VFI improved eyes with injection, VFI was positively correlated with superior, inferior, nasal and average RNFL thickness ( r=0.439, 0.356, 0.294, 0.401; all at P<0.05).In the MD improved eyes with injection, MD was positively correlated with superior, inferior, nasal and average RNFL thickness ( r=0.495, 0.424, 0.377, 0.474; all at P<0.05). Conclusions:The recovery of visual function is associated with RNFL thickness after the intravitreal injection of rAAV2-ND4 in LHON eyes.Recovery of visual acuity is better in the eyes with thicker RNFL.

Objective:To survey the teaching ability of general practitioners(GPs) in community health centers of Shanghai, and its influencing factors.Methods:A questionnaire survey on the teaching ability of general practice trainers was conducted from January to February 2017. The participants of the survey were GPs with teaching experiences from community health centers in Shanghai selected by a stratified and proportional cluster sampling method. The questionnaire included two aspects: the general information and teaching ability of the participants. The influencing factors of teaching ability were analyzed by univariate and multivariate regression analysis.Results:A total of 1 138 GPs from 116 selected community health centers participated in the questionnaire survey, among whom 63.6% (724/1 138) worked in community teaching bases and 78.5% (893/1 138) had received training for trainers. The total score of teaching ability was 38.00 (30.00, 40.00). The score of the item"interesting in teaching"was (3.46±0.80), 75%—80% of the other questions answered "yes". The score of"application of multi-teaching methods"was (3.78±0.72). Multivariate analyses showed that working for 5—9 and 10—19 years [ OR=7.14 (2.47—11.81), P=0.003; OR=5.32 (1.30—9.33), P=0.009], working in community teaching bases [ OR=13.23 (9.88—16.57), P<0.001] and receiving training for trainers [ OR=17.76 (13.80—21.71), P<0.001] were influencing factors of teaching ability. Conclusion:The main problems related to teaching ability in community GPs are lack of teaching interest and the poor application of multi-teaching methods, the relevant training is necessary for them in the future.

Objective:To observe the efficacy and safety of high frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of chronic tension-type headache (CTTH) patients.Methods:Thirty-eight patients with CTTH, admitted to our hospital from February 2019 to September 2021, were randomly divided into rTMS group and control group ( n=19). In the rTMS group, the hot spot of the right abductor pollicis brevis was surface-labeled and the resting movement threshold (RMT) was calculated; the intensity of the stimulus was then adjusted to 70% of RMT, and stimulus was then located at 5 cm in front of the previously identified hot spot of the right thumb, namely the left dorsolateral prefrontal cortex (LDLPFC); the stimulus was delivered once every Monday, Wednesday and Friday, and lasted for 4 weeks with 12 rounds of stimulation. In the control group, the hot spot was not located and RMT was not calculated; the coil was placed perpendicular to LDLPFC; and the stimulation frequency was the same as that in the rTMS group with minimum stimulation intensity. Visual analogue scale (VAS), Headache Impact Test-6 (HIT-6), simplified McGill Pain Questionnaire (SF-MPQ) were used to evaluate the subjective pain status. The electrophysiological indices in the nociceptive flexion reflex (NFR) and conditioned pain modulation (CPM) were used to evaluate the objective pain status. Adverse events during treatment and 1-month follow-up were recorded in the two groups. Results:(1) Rating scales: scores of all rating scales in the rTMS group after treatment were significantly decreased as compared with those before treatment ( P <0.05); however, no significant difference was noted in the control group ( P>0.05). After treatment, the scores of VAS, HIT-6, present pain intensity (PPI) scale, and trait anxiety inventory in the rTMS group were significantly decreased as compared with those in the control group ( Z=-4.054, P<0.001; t= -6.083, P<0.001; Z=-4.246, P<0.001; Z=-3.740, P<0.001). (2) NFR RIII parameters: as compared with that before treatment, the minimum threshold in rTMS group after treatment was significantly increased ( P<0.05). There were no significant differences in NFR RIII parameters in the control group between those after treatment and before treatment ( P>0.05). After treatment, the minimum NFR minimumthreshold in the rTMS group was significantly increased as compared with that in the control group ( P<0.05). Cold compression test results showed that as compared with basic NFR RIII area, NFR RIII area before and after treatment in both rTMS group and control group was statistically increased ( P<0.05). (3) Adverse reactions: no serious adverse reactions occurred in the two groups during treatment and follow-up. Conclusion:Treatment with rTMS in CTTH patients enjoys good short-term efficacy without obvious adverse reactions.

CCL20 and CCR6 are chemokines produced by a variety of cells. CCL20 and CCR6 combine to stimulate a series of downstream pathways, participate in the occurrence and development of various malignant tumors, and also play an important role in the invasion and metastasis of breast cancer and the process of chemotherapy resistance. Epithelial-mesenchymal transformation (EMT) is a key step in the process of tumor cell metastasis, which is characterized by loss of cell adhesion, down-regulation of E-cherherin expression, up-regulation of mesenchymal markers and fibrinectin expression, and enhancement of cell motor ability and invasion ability. This article reviews the research of CCL20-CCR6 biological axis and EMT on invasion and metastasis of breast cancer cells.

Objective:To observe the changes of vision and visual evoked potentials (VEP) in patients with Leber hereditary optic neuropathy (LHON) before and after gene therapy.Methods:A retrospective cohort study. From December 2017 to October 2018, 35 cases of 70 eyes of m11778G.A/MT-ND4 mutant LHON patients who were diagnosed in the Tongji Hospital of Huazhong University of Science and Technology and received gene therapy were included in the study. There were 30 males (87.71%) and 5 females (12.29%), with the mean age of 23.31±6.72 years. The gene therapy method was intravitreal injection of rAAV2-ND4 (recombinant adeno-associated virus carrying NADH-ubiquinone oxidoreductase subunit 4 gene) into one eye. The eye with poor visual acuity was chosen as the injection eye. If both eyes had the same visual acuity, the right eye was designated as the injection eye. Seventy eyes were divided into the injected eye group and the non-injected eye group, in which were both 35 eyes. The best corrected visual acuity (BCVA) and pattern VEP (PVEP) examinations were performed in the injected eye group and the non-injected eye group before treatment (baseline), 1, 3, and 6 months after injection. Compare the changes of BCVA and PVEP between the injected eye group and the non-injected eye group at baseline, 1 month, 3 months, and 6 months after injection. Independent sample t test, paired sample t test or two independent sample nonparametric test were performed to compare the two groups. Results:Compared with baseline, 1, 3, and 6 months after treatment, the BCVA of the injected eye group ( t=3.530, 4.962, 5.281; P=0.001, 0.000, 0.000) and the non-injected eye group ( t=3.288, 2.620, 2.252; P=0.002, 0.013, 0.031) increased, and the difference was statistically significant; there was no statistically significant difference between VEP IT ( tinjected eye group=-0.158, 1.046, -1.134; Pinjected eye group = 0.875, 0.303, 0.190; tnon-injected eye group=0.773, -0.607, -0.944; Pnon-injected eye group = 0.445, 0.548, 0.352) and VEP A ( Zinjected eye group=-0.504, -0.934, -1.065; Pinjected eye group = 0.614, 0.351, 0.287; Znon-injected eye group=-0.521, -0.115, -0.491; Pnon-injected eye group = 0.602, 0.909, 0.623). Conclusion:After gene therapy, the visual acuity of the injected and non-injected eyes of LHON patients improved; PVEP did not change significantly, and remained stable compared with baseline.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective:To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients.Methods:The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed.Results:The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively ( P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively ( P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm 3, the median survival time of SIB and No-SIB group was 34.7 and 30.3 months ( P=0.155), respectively. In the patients whose GTV volume>50 cm 3, the median survival time of SIB and No-SIB group was 16.1 and 20.1 months ( P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group ( P<0.001). Conclusions:The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.