Objective To investigate the synaptopathy of hidden hearing loss mice,and to observe the synapses of the cochlear inner hair cell after temporary threshold shift of noise exposure.Methods Mice were divided into normal control group and experiment group,the latter was exposed under noise of 98 dB SPL for 2 h to establish the model of temporary threshold shift.Mice cochleae of the two groups were dissected and prepared with whole mount and immunostaining.Cellular morphology was observed under confocal laser scanning microscope.Cochlear lengths were measured through cochlear frequency map to localize hair cells in different frequency regions.Then,3-D morphometry of synapses was constructed by Amira software to observe pre-synaptic ribbons,post-synaptic receptors and its pathological changes.Results In control group,each cochlear nerve fiber contacted a single inner hair cell by a single synapse,each inner hair cell had 5-30 synapses contacting cochlear nerve fibers.The larger ribbons patched smaller receptors located in the modiolar side,and the smaller ribbons patched larger receptors located in the pillar side.While in experiment group,noise overexposures caused moderate or completely reversible thresholds shift,i,e.,distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) thresholds increased 30-40 dB.Although returned to normal after 2 weeks,ABR wave Ⅰ amplitudes recovered to only 46.1 ％ of pre-exposure amplitudes.There was 41.3％ synapses loss of inner hair cell,but there was no loss of inner hair cells and spiral ganglion neurons.Conclusions Threshold test is not sensitive to degeneration and loss of synapse in mice inner hair cells,while super threshold test is sensitive to it.

Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. We have previously identified the benzoyl sulfathiazole derivative II as a non-competitive PTP1B inhibitor with in vivo insulin sensitizing effects. Preliminary SAR study on this compound series has been carried out herein, and thirteen new compounds have been designed and synthesized. Among them, compound 10 exhibited potent inhibition against human recombinant PTP1B with the IC50 value of 3.97 micromol x L(-1), and is comparable to that of compound II.

Objective To study the effect of repairing limbs bone defect by using uncellular tissue engineering complex of autolegous red bone marrow wrapped by facial flap with vessels to provide evidence for clinical application. Methods Nineteen cases of limbs bone defect were chosen, among them, 3 cases were with benign bone tumor,6 cases were with open fracture causing bone defect and 10 cases were with bone hypotoxic infection after operation. Took autolegous red bone marrow to prepare uncelluar tissue engineering complex with osteoinduction active material (OAM) containing bone morphogenetic protein (BMP). Prepared a facial flap with capillary network originating from an anonymos vessel adjacent to the bone defect,wrappad the tissue engineering bone and filled the bone defect. On a certain time after the operation, the patients were tested by X-ray. Results All the 19 cases were followed up in 1st,3rd,6th, 10th, 12th and 18th month after the operation. There were 3 cases that the implanted tissue engineering bone completely replaced the bone defect in 6th month displayed on X-ray,6 cases in 10th month,9 cases in 12th month and 1 case in 18th month. None of the cases had bone infection or bone absorption. Osteanagenesis and bone molding had come true in all cases. Conclusions The uncellular tissue engineering complex of autolegous red bone marrow wrapped by facial flap with vessels shows double effects in inducing osteanagenesis and the vascularization, and it is feasible in the recovery of large area bone defect. The complex can promote bone recovery and advance the quality and quantity of osteanagenesis.

Objective To investigate the diagnosis and treatment in patients with acute myocardial infarction (AMI) and complicated left ventricular wall rupture (LVWR). Methods A retrospective analysis was made on the clinical features, diagnosis and successful treatment in three AMI patients with LVWR from December 2015 to April 2016. Results Three cases were included in this study. Case 1, the mesh like cardiac rupture after AMI was diagnosed by ultrasonic Doppler. Emergency revascularization was performed due to the combined cardiac shock, and the infarct related artery was opened. The vasoactive drugs were used after revascularization to reduce ventricular pressure load and volume load in the haemodynamic monitoring, and anticoagulation, antiplatelet agents were less used or discontinued to promote local thrombus healing of ventricular rupture. Case 2 was a recurrent myocardial infarction patient. LVWR was diagnosed by ultrasonic Doppler one day after emergency operation. The ruptured ventricular wall was encapsulated by thrombus. The drug therapy was effective in hemodynamic monitoring. LVWR was further confirmed by cardiac CT after clinical stabilization. Case 3 was diagnosed LVWR by ultrasonic Doppler four days after AMI. Because the ruptured ventricular wall was limited by incompletely organized thrombus, and the haemodynamic condition was stable, selective surgical repair of rupture after coronary angiography was performed. Conclusion The effective drug therapy combined with percutaneous coronary intervention and surgical repair can reduce the risk of death in patients with LVWR after AMI.

Objective To evaluate the value of HRCT with multi-planar reformation (MPR) in the diagnosis of otosclerosis.Methods 138 ears in 129 patients with otosclerosis confirmed by surgery were evaluated retrospectively, using the MPR image along stapes as standard image, and 132 normal ears were collected as the control group.Results In the otosclerosis group, HRCT-MPR was positive in 108 ears, suspicious positive in 12 ears, and negative in 18 ears.In the control group, HRCT-MPR was positive in 4 ears,suspicious positive in 9 ears,and negative in 119 ears.The sensitivity for HRCT-MPR was 87.0％ and the specificity was 90.2％.However,with 2 mm axial CT alone ,the sensitivity was only 47.8％.The positive findings were mainly fenestral foci which related to stapes.Conclusions HRCT-MPR showed high rate of sensitivity and specificity.We recommend the MPR image along stapes as standard image for otosclerosis diagnosis.

Objective:To investigate the characteristics of bacterial community in upper gastrointestinal tumors.Methods:The study population was patients with upper gastrointestinal tumors (esophageal cancer and gastric cancer). Gastroscopy was performed on the enrolled patients ( n=17), and the specimens were taken from the tumor sites. At the same time, non-tumor tissues more than 4 cm away from the tumor tissues were taken as the control. After total DNA was extracted and purified, high-throughput 16S DNA gene sequencing was used to detect the microbiota in tumor tissues and control tissues. Bioinformatics analysis was carried out and the differences between groups were compared. Results:16S DNA PCR showed that there was no significant difference in bacterial load between tumor tissues and control tissues. The α-diversity and β-diversity indexes showed that the community composition of the two groups was similar; the samples were discrete and the colony composition was different, but there was no significant difference between the two groups. The results of Venn diagram showed that there were more operational taxonomic units (OTUs) in non-tumor tissues than in tumor tissues (2 068 vs 1 358), indicating that the bacterial species in normal tissues were more abundant than those in tumor tissues. Compared with the control tissues, the percentages of Prevotellaceae ( Prevotella), Lactobacaceae ( Lactobacillus) and Fusobacteriaceae ( Fusobacterium) in tumor tissues were relatively higher (the average percentage was more than twice that of the control). Further paired comparison of the top ten bacteria in the family and genus abundance of the two groups of samples showed that Pseudomonas decreased significantly in tumor tissues at the family ( P=0.041) and genus ( P=0.041) levels, while Prevotella was significantly enriched in tumor tissues at the family ( P=0.031) and genus ( P=0.007) levels. Conclusions:The bacterial community in the tumor microenvironment of the upper gastrointestinal tumor changed, and the species enriched in the tumor site were mainly oral common anaerobic bacteria, such as Prevotellaceae ( Prevotella), Lactobacaceae ( Lactobacillus) and Fusobacteriaceae ( Fusobacterium), especially Prevotellaceae ( Prevotella).

Objective:To investigate the effects of early percutaneous coronary intervention (PCI) on myocardial perfusion and left ventricular function in patients with acute ST-segment elevation myocardial infarction (STEMI) after thrombolysis.Methods:A total of 108 patients with STEMI treated in the Second Hospital of Hebei Medical University from January 2020 to December 2022 were divided into early PCI following thrombolysis group ( n=65) and primary PCI (pPCI) group ( n=43). The general clinical data, and the parameters of routine echocardiography at 1 day after PCI and before discharge were compared between the two groups. Myocardial contrast echocardiography (MCE) was used to evaluate myocardial perfusion at 1 day after PCI and before discharge. Results:There were no significant differences in general clinical data between the early PCI following thrombolysis group and the pPCI group (all P>0.05). The left ventricular ejection fraction (LVEF) in the early PCI following thrombolysis group and pPCI group before discharge was significantly higher than that on the 1st day after PCI(both P<0.05). The difference of LVEF was significant between the early PCI following thrombolysis group and the pPCI group before discharge and 1 day after PCI ( P<0.05). Compared with 1 day after PCI, the global longitudinal strain (LVGLS) of left ventricle increased in early PCI following thrombolysis group and pPCI group before discharge(both P<0.05). The difference of LVGLS between early PCI following thrombolysis group and pPCI group before discharge and 1 day after discharge was statistically significant( P<0.05). There were no significant differences in left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left atrial volume (LAV), ratio of mitral early diastolic velocity to late diastolic velocity (E/A), mean early diastolic velocity of mitral annulus (Em) and E/Em 1 day after PCI and before discharge between early PCI following thrombolysis group and pPCI group (all P>0.05). MCE showed that the MCE score index of early PCI following thrombolysis group and pPCI group before discharge was significantly lower than that of 1 day after PCI(both P<0.001). Compared to the 1 day after PCI, the early PCI following thrombolysis group showed a significant increase in the proportion of normal microvascular perfusion (nMVP) and a decrease in the proportion of delayed microvascular perfusion (dMVP) and microvascular obstruction (MVO) before discharge (all P<0.05). In contrast, the pPCI group demonstrated a significant decrease in the proportion of both nMVP and dMVP before discharge compared to the first day after PCI (all P<0.05). However, the decrease in the proportion of MVO was not statistically significant ( P>0.05). Conclusions:Early PCI following thrombolysis and pPCI can enhance left ventricular systolic function and myocardial perfusion in patients with acute ST-elevation myocardial infarction. Early PCI following thrombolysis may offer additional advantages in improving left ventricular systolic function and myocardial perfusion.

BACKGROUND: Primary lung squamous carcinoma that produces alpha-fetoprotein (AFP) is rare and only four related cases have been reported so far. The specific reasons for elevated serum level of AFP and effective treatment regimens for AFP-producing lung squamous carcinoma are not clear. This paper reports the diagnosis and treatment of AFP-producing lung squamous carcinoma so as to provide some references for similar cases in clinical practice. METHODS: The diagnosis and treatment of an AFP-producing lung squamous carcinoma patient admitted to the Shandong Cancer Hospital on October 23, 2020 was retrospectively analyzed, and literatures were reviewed. RESULTS: A 52-year-old male patient was diagnosed as T4N3M0 stage, IIIc right upper lobe lung squamous cell carcinoma with mediastinal lymph node metastasis and multiple metastases in the lung. The main tumor marker was abnormally increased serum AFP. After the rapid progression of two lines chemotherapy, the patient was given anlotinib combined with carrizumab as third-line treatment. The efficacy evaluation reached to partial response (PR) and stable disease (SD) after 2 and 4 cycles of treatment, respectively. The treatment regimen was replaced with albumin paclitaxel plus carrizumab due to gastrointestinal bleeding after the fifth cycle. The patient's condition was under continuous control. CONCLUSIONS The AFP-producing lung squamous carcinoma patient had a good response to anlotinib and immunotherapy in the case report, which may provide some guidances for the clinical practice and the research on AFP-producing lung squamous carcinoma.
Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell/drug therapy* ; Humans ; Lung ; Lung Neoplasms/drug therapy* ; Male ; Middle Aged ; Retrospective Studies ; alpha-Fetoproteins

Based on a non-competitive and selective PTP1B inhibitor reported by us previously, thirty-nine benzamido derivatives were designed and synthesized as novel PTP1B inhibitors. Among them, twelve compounds exhibited IC values at micromolar level against human recombinant PTP1B, and most of them exhibited significant selectivity to PTP1B over TC-PTP and CD45. Further evaluation of the most potent compound on high-fat diet (HFD)-induced insulin-resistant (IR) obese mice indicated that could modulate glucose metabolism and ameliorate dyslipidemia simultaneously.

Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.
Animals ; Environmental Exposure ; Epigenesis, Genetic ; Female ; Humans ; Male ; Mammals/genetics* ; Pregnancy ; RNA, Small Untranslated/genetics* ; Spermatozoa