Objective:To identify the differentially expressed proteins that caused hippocampal damage after liver ischemia-reperfusion (I/R) in rats.Methods:Eighteen clean-grade healthy juvenile male Sprague-Dawley rats, aged 2 weeks, weighing 20-30 g, were divided into 2 groups ( n=9 each) using a random number table method: sham operation group (S group) and liver I/R group (IR group). A rat model of liver I/R injury was prepared by restoring perfusion after 1 h of liver ischemia. The rats were sacrificed after being anesthetized at day 3 of reperfusion, and the hippocampal tissue was isolated and analyzed to obtain gene expression profiles. Differentially expressed genes were identified using the R software, and further protein interaction networks were constructed through Cytoscape and Kyoto Encyclopedia Genes and Genomes pathway analysis to determine the differentially expressed proteins. Quantitative real-time polymerase chain reaction and Western blot were used for validation. Results:A total of 45 differentially expressed proteins were identified by the proteomic analysis of hippocampal tissues, including 36 significantly up-regulated proteins and 9 significantly down-regulated proteins. The proteins with significant expression related to injury were identified from the PPI network complex using the CytoHubBA plug-in cystscape: Ras-related C3 botulinum toxin substrate (RAC2), HRAS, phosphatidylinositol-3-kinase inhibitor phosphatase and tensin homologue (PTEN), and N-methyl-D-aspartate ionotropic glutamate receptor 2b (GRIN2b). The results of quantitative real-time polymerase chain reaction and Western blot showed that the expression of RAC2, HRAS, PTEN, and GRIN2b in the hippocampal tissue was significantly up-regulated in IR group compared with S group ( P<0.05). The results of Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that differentially expressed proteins were significantly enriched in the expression of PD-L1 and its checkpoint pathway, long-term potentiation, and regulation of the Wnt signaling pathway in cancer. Conclusions:The mechanism by which liver I/R induces hippocampal injury may be related to the up-regulation of the expression of RAC2, HRAS, PTEN and GRIN2b in rats.

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.

Objective To carry out accurate quantative evaluation of MRI scanning noise based on laser vibrometry technology.Methods Skull and spine MRI was performed with mute and conventional sequences.A laser vibrometry device was used to sample the surface vibration noise at the outer edge of the inspection hole of MRI system according to GB/T 16539-1996 Acoustics—Determination of sound power levels of noise sources using vibration velocity—Measurement for seal machinery,and the indicators of sound power level,sound pressure level and perceived noise level obtained by the three calculation methods(LPN1,LPN2 and LPN3)were analyzed with some dedicated MRI noise analysis software.Results The peak sound pressure levels for conventional and mute sequences of skull scanning were 81 and 63 dB(A),respectively,and mute sequence reduced the noise level significantly;the peak sound pressure levels for conventional and mute sequences of spine scanning were 79 and 75 dB(A),respectively,and the noise reduction level was significantly lower than that of skull scanning.Significant differences in noise reduction were not found in spine scanning sequences,while were found in skull scanning sequences.During spine and skull scanning LPN1,LPN2 and LPN3 obtained by the three calculation methods of conventional and mute sequences were all higher than the overall sound power and overall pressure levels obviously.Conclusion Mute sequence can not realize linear noise reduction for the whole frequency band,the perceived noise of the human ear during MRI scanning is related directly to the scanning sequence,and there may be some bias when only one physical indicator is involved in the noise evaluation of MRI system.[Chinese Medical Equipment Journal,2024,45(10):20-24]

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

ObjectiveSorafenib is a first-line only drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Resistance to sorafenib means that treatment outcomes are often unsatisfactory. Although the mechanism underlying sorafenib resistance remains unclear, resistance may occur through Akt signaling pathway activation in HCC. Dihydrotanshinone (DHT), a lipophilic component of traditional Chinese medicine Salvia miltiorrhiza Bunge, has multiple anti-tumor activities and inhibits Akt activation. The effect and mechanism of DHT combined with sorafenib on HCC have not been investigated. In this study, we investigate whether DHT potentiates the anti-cancer activities of sorafenib against HCC. MethodsIn this study, the effects of sorafenib and DHT on the viability, apoptosis and drug sensitivity of Huh7 and HepG2 cells were verified by Cell Counting Kit-8 (CCK-8) and flow cytometry. Akt, P-Akt, Caspase3, GSK-3β, P-GSK-3β, ribosomal protein S6 kinase (S6K), P-S6K, Cyclin D1, Bcl-xl, Bcl-2, and Bax expression levels were analyzed via Western blot. All data were statistically compared using one-way analysis of variance (ANOVA) and Dunnett test. Statistical analysis using SPSS 20.0 statistical software. ResultsDHT inhibit proliferation and promote apoptosis in HCC cells by reducing Akt activation. DHT inhibits the expression and activation of Akt downstream factors, including GSK-3β and S6K, which regulate the apoptotic response and are activated and upregulated by sorafenib treatment. Both sorafenib and DHT downregulate cyclin D1 expression and DHT upregulates Bax expression and downregulates Bcl-2 and Bcl-xl expression. However, sorafenib had little influence on Bcl-2 family protein expression. ConclusionDHT may enhance the proliferation inhibition and apoptosis induction of sorafenib in HCC cells by inhibiting the activation of Akt signaling pathway, thus enhancing the anticancer effect of sorafenib.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

Objective: To investigate the infection sources and the transmission chains of three outbreaks caused by 2019-nCoV Omicron variant possibly spread through cross-border logistics in Beijing. Methods: Epidemiological investigation and big data were used to identify the exposure points of the cases. Close contacts were traced from the exposure points, and the cases' and environmental samples were collected for nucleic acid tests. Positive samples were analyzed by gene sequencing. Results: The Omicron variant causing 3 outbreaks in Beijing from January to April, 2022 belonged to BA.1, BA.1.1 and BA.2. The outbreaks lasted for 8, 12 and 8 days respectively, and 6, 42 and 32 cases infected with 2019-nCoV were reported respectively. International mail might be the infection source for 1 outbreak, and imported clothes might be the infection sources for another 2 outbreaks. The interval between the shipment start time of the imported goods and the infection time of the index case was 3-4 days. The mean incubation period (Q₁, Q₃) was 3 (2,4) days and the mean serial interval (Q₁, Q₃) was 3 (2,4)days. Conclusions: The 3 outbreaks highlighted the risk of infection by Omicron variant from international logistics-related imported goods at normal temperature. Omicron variant has stronger transmissibility, indicating that rapid epidemiological investigation and strict management are needed.
Humans ; Beijing ; SARS-CoV-2 ; COVID-19 ; Disease Outbreaks ; China/epidemiology*

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4,2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.