AIM:To explore the role of miR-195-5p in mediating trastuzumab resistance in gastric cancer and to validate its potential as a therapeutic target along with its target gene GPRC5A.METH-ODS:Trastuzumab-resistant gastric cancer cell lines(NCI-N87 and MKN45)were established.Cell viabili-ty under trastuzumab treatment was assessed us-ing CCK-8 assays.Expression levels of miR-195-5p were determined by RT-qPCR.Transfection with miR-195-5p mimics was performed to evaluate changes in trastuzumab sensitivity and prolifera-tion.GPRC5A expression was also measured by RT-qPCR,and the targeting relationship between miR-195-5p and GPRC5A was confirmed using a dual-lu-ciferase reporter assay.RESULTS:Parental cells showed higher sensitivity to trastuzumab than re-sistant cells,with miR-195-5p expression signifi-cantly lower in the latter.Overexpression of miR-195-5p in resistant cells enhanced trastuzumab sen-sitivity and reduced proliferation.GPRC5A was found to be upregulated in resistant cells,and miR-195-5p directly targeted GPRC5A,affecting cell pro-liferation under trastuzumab treatment.CONCLU-SION:miR-195-5p may regulate trastuzumab sensi-tivity in gastric cancer by targeting GPRC5A,sug-gesting potential as a molecular marker for trastu-zumab therapy guidance.

AIM:To explore the role of miR-195-5p in mediating trastuzumab resistance in gastric cancer and to validate its potential as a therapeutic target along with its target gene GPRC5A.METH-ODS:Trastuzumab-resistant gastric cancer cell lines(NCI-N87 and MKN45)were established.Cell viabili-ty under trastuzumab treatment was assessed us-ing CCK-8 assays.Expression levels of miR-195-5p were determined by RT-qPCR.Transfection with miR-195-5p mimics was performed to evaluate changes in trastuzumab sensitivity and prolifera-tion.GPRC5A expression was also measured by RT-qPCR,and the targeting relationship between miR-195-5p and GPRC5A was confirmed using a dual-lu-ciferase reporter assay.RESULTS:Parental cells showed higher sensitivity to trastuzumab than re-sistant cells,with miR-195-5p expression signifi-cantly lower in the latter.Overexpression of miR-195-5p in resistant cells enhanced trastuzumab sen-sitivity and reduced proliferation.GPRC5A was found to be upregulated in resistant cells,and miR-195-5p directly targeted GPRC5A,affecting cell pro-liferation under trastuzumab treatment.CONCLU-SION:miR-195-5p may regulate trastuzumab sensi-tivity in gastric cancer by targeting GPRC5A,sug-gesting potential as a molecular marker for trastu-zumab therapy guidance.

Objective:To evaluate the efficacy and safety of θ short burst rapid pulse stimulation(TBS)in treating schizophrenia by meta-analysis.Methods:Randomized controlled trials(RCTS)on TBS in the treatment of schizophrenia were searched from CNKI,Wanfang,VIP,China Biomedicine,Web of science,PubMed,Embase and Cochrane Library databases to December 2022.The main study indicator was the Positive and Negative Symptoms Scale(PANSS).Risk quality assessment of the included literatures was performed by two reviewers and statistical analysis was performed using RevMan5.3.Results:A total of 13 RCTS with 641 patients were included.Meta-anal-ysis showed that TBS targeting the left dorsolateral prefrontal cortex(DLPFC)with intervention duration longer than 2 weeks decreased the PANSS total scores(WMD=-4.63,95％CI:-5.75--3.51,P＜0.001),positive symptom scores(WMD=-1.13,95％CI:-2.00--0.26,P＜0.05),negative symptom scores(WMD=-2.51,95％CI:-2.77--1.53,P＜0.001)and general psychopathological symptom scores(WMD=-1.20,95％CI:-1.80--0.60,P＜0.001).The adverse reactions of TBS included dizziness,and no serious adverse e-vents were reported.Conclusion:TBS has high safety,and stimulation of left dorsolateral prefrontal cortex targets for more than 2 weeks could effectively improve psychiatric symptoms in patients with schizophrenia.

BACKGROUND:Adjustable piezoelectric effect can promote tissue regeneration and repair.Piezoelectric materials are widely used in weight-bearing tissue engineering. OBJECTIVE:To prepare a piezoelectric film material that can promote bone regeneration,and to explore its structural characterization,electrical output performance,biocompatibility,and effect of electrical output on osteogenic differentiation of rabbit bone marrow mesenchymal stem cells. METHODS:Using poly-3-hydroxybutyrateco/4-hydroxybutyrate(P34HB)as raw material,barium calcium stannate titanate powder(Ba0.94Ca0.06Sn0.08Ti0.92O3,BCST)was added according to mass ratios of 0%,5%,10%,15%,and 20%.Dichloromethane was added to solve P34HB,and the thickness of 150-200 μm BCST/P34HB piezoelectric film was prepared by vacuum drying method.After polarization in the oil bath,the surface morphology,crystal phase composition,piezoelectric coefficient and open circuit voltage were tested.The effect of BCST/P34HB electrical output at 110 Hz and 0.25 N force on the proliferation and osteogenic differentiation of rabbit bone marrow mesenchymal stem cells was tested. RESULTS AND CONCLUSION:(1)Scanning electron microscopy,X-ray diffraction,water contact angle,piezoelectric coefficient and electrical output performance tests showed that when the mass ratio of BCST increased to 20%,the BCST/P34HB piezoelectric film had good piezoelectric properties(d33=5.9 pC/N)and electrical output performance(180 mV),which was closer to the suitable range of 500 mV for electrical stimulation.(2)Live and dead staining showed that on the first day of co-culture,15%group and 20%group showed less red fluorescence.On the 5th day of culture,the number of green fluorescence in each group was significantly higher than that on the first day,and the red fluorescence was not observed in the 10%,15%and 20%groups,and only a small amount of red fluorescence was observed in the 0%and 5%groups.(3)On the 1st,3rd and 5th days of co-culture with rabbit bone marrow mesenchymal stem cells,Almar blue staining exhibited that the number of cells in each group showed an increasing trend with the increase of time.On the 5th day of culture,the number of cells in the 20%group was significantly more than that in the 0%group(P<0.05).(4)On day 10 of osteogenic induction,alkaline phosphatase staining results showed that the positive rate of the 20%group was significantly higher than that of the 0%group(P=0.000 1).On day 21,alizarin red staining and quantitative analysis of calcium nodules showed a similar trend to alkaline phosphatase staining.Compared with the 0%group,the 15%group and 20%group showed significant differences(P<0.01,P<0.000 1).(5)The results showed that 20%BCST/P34HB films had good piezoelectric properties,electrical output properties,biocompatibility and the ability of promoting osteogenic differentiation of bone marrow mesenchymal stem cells.

Objective:To investigate the arterial blood pressure levels of fighter pilots and to analyze the risk factors associated with blood pressure in fighter pilots.Methods:A retrospective analysis was conducted on the physical examination data and questionnaire data of the fighter pilots who underwent aeromedical assessment at Air Force Healthcare Center for Special Services Hangzhou. They were divided into hypertension group [SBP≥140 mmHg (1 mmHg=0.133 kPa) and (or) DBP≥90 mmHg], normal high blood pressure group [120 mmHg≤SBP<140 mmHg and (or) 80 mmHg≤DBP<90 mmHg] and normal blood pressure group (SBP<120 mmHg and DBP<80 mmHg) according to the blood pressure level. The differences of physiological and biochemical indicators among the pilots of 3 groups were compared, and the risk factors affecting blood pressure were analyzed by multiple Logistic regression.Results:A total of 414 fighter pilots were included, with 9 (2.17%) in the hypertension group, 274 (66.18%) in the normal high blood pressure group, and 131 (31.64%) in the normal blood pressure group. There were significant differences in age, flying hours, body mass index, waist circumference, fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol, and blood uric acid among the pilots of different blood pressure groups ( F=2.97-11.08, all P<0.05), but no significant difference in HDL-C ( P>0.05). The risk factors for increased the blood pressure of fighter pilots included alcohol consumption ( OR=9.865, P=0.021), salt consumption ( OR=8.971, P=0.033), blood uric acid ( OR=1.013, P=0.046), BMI ( OR=1.431, P=0.001) and waist circumference ( OR=1.340, P=0.039). The protective factor was the consumption of vegetables and fruits ( OR=0.623, P=0.033). Conclusions:High sodium diet, overweight or obesity, excessive alcohol consumption, increased blood uric acid and low consumption of vegetables and fruits may be the risk factors result in high blood pressure of fighter pilots.

Objective:To study the learning curve of percutaneous patent foramen ovale (PFO) occlusion guided solely by transthoracic echocardiography (TTE), as well as the success rate and safety of the learning curve.Methods:To retrospectively analyze these patients with indications for PFO occlusion admitted in our department from April 2021 to April 2022, and obtained 100 samples the author's initial cases guided solely by TTE, including 25 men and 75 women, with a mean age of (48.22±10.44) years old.Analyze preoperative baseline data: gender, age, height, weight, body mass index, the tunnel length and size of the PFO measured by transesophageal echocardiography, the grade of contrast-transcranial doppler test, combined atrial septal aneurysm, etc.Operation time, success rate, and complications were analyzed in all patients.Results:With the accumulation of cases, the operation time gradually shortened, accumulated to about 50 cases, the operation time has significantly shortened ( P<0.05), and the learning curve was leveled off after 50 cases ( P<0.05), there was statistical difference.The comparison of the success rate and complication of cases within the learning curve and those after completing the learning curve was no statistical significance( P>0.05). Conclusion:The learning curve of percutaneousc closure of patent foramen ovale guided solely by TTE is long, requiring about 50 cases to complete the learning curve. The success rate and safety of the learning curve are high. This procedure is worth popularizing.

Objective:To investigate the arterial blood pressure levels of fighter pilots and to analyze the risk factors associated with blood pressure in fighter pilots.Methods:A retrospective analysis was conducted on the physical examination data and questionnaire data of the fighter pilots who underwent aeromedical assessment at Air Force Healthcare Center for Special Services Hangzhou. They were divided into hypertension group [SBP≥140 mmHg (1 mmHg=0.133 kPa) and (or) DBP≥90 mmHg], normal high blood pressure group [120 mmHg≤SBP<140 mmHg and (or) 80 mmHg≤DBP<90 mmHg] and normal blood pressure group (SBP<120 mmHg and DBP<80 mmHg) according to the blood pressure level. The differences of physiological and biochemical indicators among the pilots of 3 groups were compared, and the risk factors affecting blood pressure were analyzed by multiple Logistic regression.Results:A total of 414 fighter pilots were included, with 9 (2.17%) in the hypertension group, 274 (66.18%) in the normal high blood pressure group, and 131 (31.64%) in the normal blood pressure group. There were significant differences in age, flying hours, body mass index, waist circumference, fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol, and blood uric acid among the pilots of different blood pressure groups ( F=2.97-11.08, all P<0.05), but no significant difference in HDL-C ( P>0.05). The risk factors for increased the blood pressure of fighter pilots included alcohol consumption ( OR=9.865, P=0.021), salt consumption ( OR=8.971, P=0.033), blood uric acid ( OR=1.013, P=0.046), BMI ( OR=1.431, P=0.001) and waist circumference ( OR=1.340, P=0.039). The protective factor was the consumption of vegetables and fruits ( OR=0.623, P=0.033). Conclusions:High sodium diet, overweight or obesity, excessive alcohol consumption, increased blood uric acid and low consumption of vegetables and fruits may be the risk factors result in high blood pressure of fighter pilots.

ObjectiveTo analyze the hotspots and development of researches on animal-assisted intervention in the past ten years. MethodsThe researches on animal-assisted intervention from 2011 to 2021 were retrieved from the Web of Science core database, and analyzed the countries/regions, institutions, authors, cited journals, cited literature and keywords using CiteSpace. ResultsA total of 607 researches were included. The researches increased with years, while United States (230), Italy (65) and the United Kingdom (45) were the top three in the number of publications; Purdue University published the most researches (20); and Santaniello A, etc. were the high-producing authors. The key nodes of literature were mainly systematic reviews and randomized controlled trials. Animal-assisted therapy and dogs were high-frequency keywords, with 20 keywords of high centrality and 16 keywords of strongest bursting. Hotspots focused on Alzheimer's disease, depression, children, autism. Disorder and occupational therapy might be the new topics in the future. ConclusionThe animal-assisted intervention has been mainly used as a healthcare in psychology, and may be an approach of occupational therapy.

Objective:To provide insight into the clinical characteristics, therapy and prognosis of patients with radiation-induced brainstem injury after radiotherapy.Methods:From August 2013 to September 2021, 13 patients with radiation-induced brainstem injury were included in this study at Sun Yat-sen Memorial Hospital, and the general information and strategy of radiotherapy were collected. A retrospective analysis was adopted to investigate the clinical and radiological characteristics, treatment and clinical outcomes.Results:There were 13 cases in total, including 4 females and 9 males. The onset age of enrolled patients ranged from 29 to 66 years with an average of (48.15±10.23) years. The median dose targeted at tumor area was 70 Gy with in 33 fractions. The median interval between radiotherapy and the diagnosis of radiation-induced brainstem injury was 24 months. The common clinical manifestations included dysphagia, bucking dysarthria, dizziness and problem with balance. The MRI radiological features were hypointense on T1WI, hyperintense on T2WI, and irregularly enhanced with contrast. The median follow-up was 45 months. Seven cases got improvements, while 3 had no obvious efficacy and 3 cases died. No significant differences in prognosis were observed between those received traditional glucocorticoid and those received bevacizumab treatment( P=0.079). Conclusions:The common symptoms of radiation-induced brainstem injury were symptoms of posterior cranial nerves injury and ataxia. Lesions mostly happened in pons and medulla, with hypointense on T1WI and hyperintense on T2WI. Half of the patients have improved after treatment. There was no significant difference in prognosis between glucocorticoid and bevacizumab treatment.

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.