An analog PID controller-based galvanometer scanner is widely used by fractional laser medical equipment(FLME)to scan lasers across tissue surfaces,achieving the desired therapeutic effect.This type of driver,primarily composed of passive components and operational amplifiers,can only accept commands from the central controller of the FLME,with a simple hardware circuit-based fault diagnosis;thus,the safety of the FLME is compromised.To address these issues,the failure mechanisms of galvanometers and their impact on the safety of FLME are thoroughly analyzed first.Then,an adaptive limit protection method,a coil open circuit fault diagnosis,a communication timeout protection based on two handshakes,and a galvanometer control timeout protection are proposed,respectively,based on a digital driver platform,to supplement the deficiencies in the original fault diagnosis and protection system.This ensures the safety of the FLME.Finally,the effectiveness of the proposed strategies is validated through experiments.

Purpose To explore the value of deep learning ultrasound radiomics nomogram in assessing the biological characteristics of invasive metastases in invasive breast cancer.Materials and Methods A retrospective collection of ultrasound imaging data from 180 pathologically confirmed invasive breast cancer between January 2021 to December 2022 in Maoming People's Hospital was conducted,with pathological reports indicating the status of lymph node metastasis(LNM),lymphovascular space invasion(LVSI)or perineural invasion(PNI),according to the LNM/LVSI/PNI status,the three indexes were divided into the training cohort and the verification cohort by 8∶2.Based on Pyradiomics and ResNet50 deep learning extractor,1 316 radiomic features and 2 048 deep learning features were extracted,respectively.The random forest machine learning algorithm was employed to develop evaluation models,and the model scores were calculated.The deep learning radiomics nomograms were developed based on the radiomic and deep learning model scores.The receiver operating characteristic curve was used to assess the performance of the models.The Delong test was applied to analyze the performance differences between different models.Results In the evaluation of LNM,LVSI and PNI status,the area under the curve of all the nomogram in the cohorts demonstrated moderate or above assessment performance(≥0.73),with accuracies all greater than 0.70.Specifically,in the LNM evaluation,the area under the curve of the training cohort was 0.97,the accuracy was 0.93,the sensitivity was 0.88 and the specificity was 0.96.Through the Delong test,the assessment performance of the nomograms was superior to the radiomics models(LNM,Z=2.04,P=0.04;LVSI,Z=2.80,P=0.01;PNI,Z=3.52,P<0.01),and was superior to or similar to the deep learning models(LNM,Z=4.52,P<0.01;LVSI,Z=1.86,P=0.06;PNI,Z=0.31,P=0.76)in the training cohort.Conclusion The deep learning radiomics nomogram can effectively evaluate the biological characteristics of invasion and metastasis in invasive breast cancer.The nomogram improves the assessment performance by integrating the radiomic and deep learning feature information.

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKT^Ser473 and p-GSK3β^Ser9, and decreased the expression of p-STAT3^Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice ; Animals ; Male ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Marsdenia ; Proto-Oncogene Proteins c-akt ; Glycogen Synthase Kinase 3 beta ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Prostatic Neoplasms ; Apoptosis ; STAT3 Transcription Factor

Objective: To investigate the epidemiological characteristics of pulmonary tuberculosis ( PTB ) incidence and mortality in Zhejiang Province from 2016 to 2020, so as to provide the evidence for formulating the PTB control strategy. Methods: The data regarding the PTB patients in Zhejiang Province from 2016 to 2020 were collected from the Tuberculosis Management Information System of the Chinese Disease Control and Prevention Information System. The reported cases and deaths of PTB cases were descriptively analyzed by time, population and regions. Results: A total of 129 985 PTB cases were reported in Zhejiang Province from 2016 to 2020, and the overall reported incidence rate of PTB was 45.81/105, with a tendency toward a decline in the reported incidence ( χ2trend=298.899, P<0.001 ) and an annual decline rate of 3.72%. The prevalence rates of rifampicin resistance, positive etiological tests, negative etiological tests and no etiological results were 1.51%, 47.17%, 46.67% and 4.65%, respectively. A total of 546 PTB deaths occurred in Zhejiang Province from 2016 to 2020, and the reported mortality of PTB was 0.19/105, with a tendency towards a decline ( χ2trend=10.818, P<0.001) and an annual decline rate of 11.99%.The prevalence rates of rifampicin resistance, positive etiological tests, negative etiological tests and no etiological results were 1.83%, 82.97%, 13.37% and 1.83%, respectively. The highest reported incidence ( 92.18/105 ) and mortality ( 1.19/105 ) of PTB was found in patients aged 65 years and older, and farmer was the predominant occupation of PTB cases (60 774 cases, 46.75%) and dead PTB cases ( 345 cases, 63.19% ). In addition, the top three cities with the highest incidence of PTB included Quzhou City ( 66.43/105 ), Jinhua City ( 64.24/105 ) and Lishui City ( 53.91/105 ), and the top three cities with the highest mortality of PTB included Quzhou City ( 0.67/105 ), Lishui City ( 0.27/105 ) and Jiaxing City ( 0.26/105 ). Conclusions Both the reported incidence and mortality of PTB appeared a tendency towards a decline in Zhejiang Province from 2016 to 2020; however, the proportion of positive etiological tests increased. Higher attention should be paid to the elderly aged 65 years and older and and farmers, and active screening and health education are recommended; in addition, PTB control requires to be intensified in highly prevalent regions, including Quzhou City, Jinhua City and Lishui City.

Objective: To analyze the epidemiological characteristics of pulmonary tuberculosis cases at ages of 60 years and older in Quzhou City, Zhejiang Province, so as to provide the evidence for formulating the pulmonary tuberculosis control strategy among the elderly. Methods: The data pertaining to pulmonary tuberculosis cases at ages of 60 years and older in Quzhou City from 2010 to 2020 were collected through the Tuberculosis Management Information System of the China Disease Prevention and Control Information System. The trends for incidence, population distribution, diagnosis and treatment of pulmonary tuberculosis cases aged 60 years and older were analyzed using a descriptive epidemiological method. Results: Totally 8 754 pulmonary tuberculosis cases aged 60 years and older were reported in Quzhou City from 2010 to 2020, accounting for 47.65% of all pulmonary tuberculosis cases, and the number of pulmonary tuberculosis appeared a tendency towards a rise ( χ2trend=173.320, P<0.001 ), while the incidence of pulmonary tuberculosis showed a tendency towards a decline ( χ2trend=389.820, P<0.001 ), with an annual decline rate of 177.11/105. There were 4 307 smear-positive pulmonary tuberculosis cases, accounting for 58.71% of all smear-positive cases, and the number of smear-positive pulmonary tuberculosis cases showed a tendency towards a rise ( χ2trend=126.320, P<0.001 ), while the proportion of smear-positive cases showed a tendency towards a decline ( χ2trend=21.680, P<0.001 ), with an annual smear-positive rate of 87.14/105. The incidence of pulmonary tuberculosis was 256.94/105 among males and 91.43/105 among females at ages of 60 years and older ( χ2=20.903, P<0.001 ). The highest incidence of pulmonary tuberculosis was seen in patients aged 80 to 84 years ( 235.17/105 ), and farmers were the predominant occupation ( 7 171 cases, 81.92% ), while the highest number of cases was reported in Quzhou City (8 676 cases, 99.11%). There were 7 752 treatment-naïve cases ( 88.55% ), while 5 830 cases with delay in seeking healthcare services, and the proportion of delay in seeking healthcare services showed a tendency towards a rise from 2010 to 2020 ( χ2trend=4.853, P=0.028 ), with an annual mean delay rate of was 66.60%. Conclusion The incidence of pulmonary tuberculosis appeared a tendency towards a decline among patients aged 60 years and older in Quzhou City from 2010 to 2020, and the elderly aged 80 years and older and farmers should be paid more attention.

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. β-Amyloid (Aβ) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed Aβ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in Aβ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against Aβ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A₁ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the Aβ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of A₁R is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.
Action Potentials ; Adenosine ; Alzheimer Disease ; Fires ; Ibotenic Acid ; Membranes ; Neurons ; Neuroprotection ; Neuroprotective Agents ; Patch-Clamp Techniques ; Pyramidal Cells

The aim of the study was to evaluate the efficacy and safety of phloroglucinol in treatment of abdominal pain caused by acute gastroenteritis.Three hundred patients with acute abdominal pain were randomly assigned to receive 80 mg intravenous infusion of phloroglucinol injection ( treatment group,n =150 ) or 10 mg anisodamine injection (control group,n =150).The pain intensity was estimated by the VAS scores before and after the injection,meanwhile adverse reactions were also recorded.The results showed that the pain intensity was relieved significantly after 1h of the injection in both groups(P ＜0.01).The effective rate of phloroglucinol was 84.1％ (126/150),while that of anisodamine was 80.0％ (120/150).The adverse reactions of treatment group were lower than that of control group( all P ＜0.01).The results indicate that phloroglucinol can effectively relieve abdominal pain caused by acute gastroenteritis with safety.

We constructed a phage-displayed random mutation library of Tat38-61(51N/55N), for studying the molecular evolution screening of HIV-1 Tat38-61 epitope. We used primers containing the random nucleotide sequences, and introduced the random mutations at the sites of 51 and 55 amino acids coding sequences into full-length Tat sequences by overlapping PCR. With the randomly mutated full-length Tat as template, the Tat38-61(51N/55N) mutants which contained recognition sequences for the Xba I in both ends were amplified by PCR using the designed primers. The mutants were cloned into Xba I site in the phagemid vector pCANTAB5S, then the recombinants were transformed into E. coli TG1, a phage-displayed the random mutation library of Tat38-61(51N/55N) was constructed by the rescue of help virus M13KO7. The results showed that the library consisted of about 5.0 x 10(6) colonies and the phage library titer was 2.65 x 10(12) TU/mL. More than 56.50% colonies in the library were positive for insertion. Sequence analysis showed that the nucleotides encoding amino acids at the sites of 51 and 55 distributed randomly. The constructed mutation library could meet the requirements for the following molecular evolution screening, and might prepare the Tat mutants for the further study of new Tat vaccine candidates.
AIDS Vaccines ; immunology ; Escherichia coli ; genetics ; metabolism ; HIV-1 ; genetics ; Humans ; Mutation ; Peptide Fragments ; biosynthesis ; genetics ; immunology ; Peptide Library ; Recombinant Proteins ; biosynthesis ; genetics ; immunology ; tat Gene Products, Human Immunodeficiency Virus ; biosynthesis ; genetics ; immunology

Objective To construct shifting mutant of cysteine-rich region to 3?@terminal of Tat gene of human immunodeficiency virus type-1 (HIV-1) HXB2 strain, and to analyze the immunogenicity of mutant protein (Tat-cct) after prokaryotically expressed and purified. Methods The cysteine-rich region (nucleotides 64--111) of Tat gene was shifted to 3'terminal of Tat of HIV-1 HXB2 strain by polymerase chain reaction (PCR) and Tat mutant DNA sequence was obtained. Prokaryotie express plasmid pET32a-Tat-cct was constructed and transformed into E. coli BL21 (DE3), then Tat-cct protein was expressed and purified. BALB/c mice were immunized with the fusion protein Tat-cct, and immunogenicity of the immunized serum was detected by enzyme-linked immunosorbent assay (ELISA). Results The recombinant plasmid pET32a-Tat-cct expressed in E. coli BL21 (DE3) and the relative molecular mass of the purified fusion protein was 31 000. The serum antibody titer of mice immunized with Tat-cct recombinant protein was 1 : 1600, which binded specifically with both Tat-ect protein and Tat protein (amino acids 1-101). Conclusions The recombinant protein Tat-cct of Tat mutant strain can be expressed efficiently in E. coli and well retains immunogenicity, which provides valuable information for basic research of HIV-1 Tat vaccine.

Objective Deleting the cysteine-rich region (22-37 amino acids)of HIV-1 HXB2 Tat protein(whole length is 101 amino acids) to improve its stability and expression level in E.coli and to analyze the immunogenicity of Tat protein without the cystein-rich region [Tat(△C)protein]. Methods Tat DNA deleted the cysteine-rich region (64-111 nucleotides), named as Tat(△C)DNA, was obtained in vitro by PCR and cloned into pET-32a vector. pET-32a-Tat(△C)plasmid and the pET-32a-Tat plasmid were established and transformed into E.coli BL21(DE3) strains respectively to express and purify the protein. Three rabbits were vaccinated with pET-32a-Tat(△C)protein, then testify the reactivity of sera from rabbits by ELISA and Western blot. Results The dense of the purified pET-32a-Tat(△C)protein was 7.12 mg/ml,which was greatly more than pET-32a-Tat protein(1.50 mg/ml). Dimer of pET-32a-Tat protein can be observed just after the protein purification and stored at 25℃ and 4℃ for 7 days, but dimer of pET-32a-Tat(△C)protein was not formed at the same condition. Experimental rabbits were immunized with pET-32a-Tat(△C)protein and produced high titre of anti-pET-32a-Tat(△C)serum(1∶320 000), the antibody can react specifically with Tat(△C)protein, Tat protein (1-101 AA)and synthetic Tat(1-86 AA) protein. Deletion mutation of the cysteine-rich region of Tat protein was first performed in the study. Conclusion The expression level in E.coli and the stability of Tat protein deleted the cysteine-rich region can be increased greatly, and the protein remains good immunogenicity. The results may provide a novel antigen for further development of HIV-1 Tat vaccine.