ObjectiveTo establish an ultra-performance liquid fingerprint and multi-components determination method for Naomaili granules. To evaluate the quality of different batches by chemometrics， and the anti-neuroinflammatory effects of water extract and main components of Naomaili granules were tested in vitro. MethodsThe similarity and common peaks of 27 batches of Naomaili granules were evaluated by using Ultra performance liquid chromatography （UPLC） fingerprint detection. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） technology was used to determine the content of the index components in Naomaili granules and to evaluate the quality of different batches of Naomaili granules by chemometrics. LPS-induced BV-2 cell inflammation model was used to investigate the anti-neuroinflammatory effects of the water extract and main components of Naomaili granules. ResultsThe similarity of fingerprints of 27 batches of samples was > 0.90. A total of 32 common peaks were calibrated， and 23 of them were identified and assigned. In 27 batches of Naomaili granules， the mass fractions of 14 components that were stachydrine hydrochloride， leonurine hydrochloride， calycosin-7-O-glucoside， calycosin，tanshinoneⅠ， cryptotanshinone， tanshinoneⅡ_A， ginsenoside Rb₁， notoginsenoside R₁， ginsenoside Rg₁， paeoniflorin， albiflorin， lactiflorin， and salvianolic acid B were found to be 2.902-3.498， 0.233-0.343， 0.111-0.301， 0.07-0.152， 0.136-0.228， 0.195-0.390， 0.324-0.482， 1.056-1.435， 0.271-0.397， 1.318-1.649， 3.038-4.059， 2.263-3.455， 0.152-0.232， 2.931-3.991 mg∙g^-1， respectively. Multivariate statistical analysis showed that paeoniflorin， ginsenoside Rg₁， ginsenoside Rb₁ and staphylline hydrochloride were quality difference markers to control the stability of the preparation. The results of bioactive experiment showed that the water extract of Naomaili granules and the eight main components with high content in the prescription had a dose-dependent inhibitory effect on the release of NO in the cell supernatant. Among them， salvianolic acid B and ginsenoside Rb₁ had strong anti-inflammatory activity， with IC₅₀ values of （36.11±0.15） mg∙L^-1 and （27.24±0.54） mg∙L^-1， respectively. ConclusionThe quality evaluation method of Naomaili granules established in this study was accurate and reproducible. Four quality difference markers were screened out， and eight key pharmacodynamic substances of Naomaili granules against neuroinflammation were screened out by in vitro cell experiments.

ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction （清肺渗湿汤） combined with western medicine for patients with bronchial asthma of heat wheezing syndrome， and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group， each group with 43 participants. The control group received conventional western medicine， and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group， 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness； secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， asthma control test （ACT） score， pulmonary function indices such as forced expiratory volume in 1 second （FEV₁）， forced vital capacity （FVC）， peak expiratory flow （PEF）， serum inflammatory factor levels including interleukin-4 （IL-4）， tumour necrosis factor-α （TNF-α）， and high-sensitivity C-reactive protein （hs-CRP）， and immune function indices including CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺. All outcome measures were evaluated before and after treatment. Vital signs were monitored， and electrocardiography， blood routine， urine routine， liver function， and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% （39/40）， which was significantly higher than that of the control group （85.0%， 34/40， P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， IL-4， TNF-α， hs-CRP， and CD8⁺ levels， as well as increased ACT scores， CD3⁺， CD4⁺， CD4⁺/CD8⁺， FEV₁， FVC， and PEF levels （P＜0.05 or P＜0.01）. Moreover， the improvements in these indices were more significant in the treatment group than in the control group （P＜0.05 or P＜0.01）. No significant abnormalities in safety indicators were observed in either group， and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms， pulmonary function， and clinical effectiveness， with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.

Antibody-drug conjugates （ADCs） are a novel class of anti-tumor agents composed of a targeted monoclonal antibody， a cytotoxic drug， and a linker connecting the two. They combine the high specificity of antibodies with the potent cytotoxicity of chemotherapeutic agents. Triple-negative breast cancer （TNBC） is characterized by high aggressiveness， elevated risks of recurrence and metastasis， and poor prognosis， largely due to the lack of effective therapeutic targets. This review summarizes the research progress of ADCs in the treatment of TNBC. It has been found that ADCs targeting human epidermal growth factor receptor 2 （such as trastuzumab deruxtecan）， trophoblast cell surface antigen 2 （such as sacituzumab govitecan and datopotamab deruxtecan）， zinc transporter LIV-1 （such as ladiratuzumab vedotin）， HER-3 （such as patritumab deruxtecan）， epidermal growth factor receptor （such as AVID100）， and glycoprotein non-metastatic melanoma protein B （such as glembatumumab vedotin） have all demonstrated promising therapeutic effects against TNBC. Despite challenges including acquired resistance and treatment-related toxicities， ADCs are undoubtedly reshaping the therapeutic landscape for TNBC and are expected to occupy a more central position in TNBC treatment in the future.

Objective: To study the correlation between short sleep duration and screening myopia among primary and middle school students in Beijing, so as to provide a scientific basis for the comprehensive prevention and control of myopia among students. Methods: Using a stratified cluster random sampling, 25 593 primary and middle school students from 16 districts of Beijing were selected from September to November 2023. The National Common Diseases and Health Influencing Factors Monitoring Survey Questionnaire was used to conduct a questionnaire survey, and visual acuity was tested according to the Specification for the Screening of Refractive Error in Primary and Middle School Students. The reporting rates of short sleep duration and detection rates of screening myopia among primary and middle school students were compared using the Chi square test. Binary Logistic regression was used to analyze the correlation between short sleep duration and screening myopia. Results: About 68.63% of students reported short sleep duration. There was a statistically significant difference in the reporting rate of short sleep duration among students in different school stages ( χ 2=981.18, P <0.01), with the lowest reporting rate of vocational high school students (47.07%) and the highest reporting rate of ordinary high school students (76.17%). The detection rates of screening myopia among primary school students ( 57.09% ) and middle school students (76.53%) who reported short sleep duration were higher than those who reported enough sleep duration (52.65%, 71.94%), with satistically significant differences ( χ 2=14.83, 17.96, P <0.01). The results of binary Logistic regression analysis showed that primary and middle school students with short sleep duration had a higher risk of developing screening myopia, compared to students with enough sleep duration ( OR =1.25); after adjusting for confounding factors such as educational stage, gender, region, boarding situation, primary and secondary school students with short sleep duration still had a higher risk of screening myopia ( OR =1.26) ( P <0.01). The analysis results stratified by educational stage showed that primary school students from grades 4-6 and middle school students with short sleep duration had a higher risk of screening myopia ( OR=1.18, 1.20, P <0.01). Conclusions Primary and secondary school students in Beijing with short sleep duration sleep have a higher risk of developing screening myopia. Families, schools, and society should ensure enough sleep duration to reduce the occurrence of myopia among students.

BACKGROUND:The mechanisms underlying the occurrence of pressure injuries are complex,and it is not entirely clear which factors play a central role in the development of pressure injuries and how these factors operate. OBJECTIVE:To investigate the relationship between Piezo-type mechanosensitive ion channel component 1(Piezo1)and the occurrence of pressure injuries. METHODS:(1)Cellular experiment:Human immortalized keratinocytes(HaCaT)were treated with Yoda1,a Piezo1 agonist,at different concentrations.Cell viability,calcium ion influx,Piezo1,and apoptosis-related protein expression were detected.(2)Animal experiment:Twelve Sprague-Dawley rats were randomly divided into a control group and three experimental groups,with three rats in each group.The control group was not subjected to pressure,while in the three experimental groups,magnets with a thickness of 1,2,and 3 mm were used to press on both sides of the rats'back for 1 hour,respectively,to establish the animal models of pressure injuries.After modeling,all traumatic tissues were excised and subjected to hematoxylin-eosin,Masson,immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION:Cellular experiments:The results of live/dead cell staining showed that HaCaT cell apoptosis increased with the increase of Yoda1 concentration(0,2.5,5,and 10 μmol/L),and calcium ion influx increased with the increase of Yoda1 concentration(0,5,and 10 μmol/L),as well as with the prolongation of treatment time.Western blot assay results showed an increase in the expression of BAX,TG2,and PIEZO1 and a decrease in the expression of the expression of Bcl-2 protein in HaCaT cells in 5 and 10 μmol/L Yoda1 groups compared with the control group(0 μmol/L Yoda1).Animal experiments:The results of hematoxylin-eosin and Masson staining showed that the skin structure of the three experimental groups was damaged at the compression site,there was subcutaneous fat liquefaction and necrosis,and collagen was sparse and disorganized,and damage to the skin structure at the compression site was aggravated with the increase of magnet thickness.Immunofluorescence staining and western blot results showed that compared with the control group,the expression of BAX,TG2,Yap1 and PIEZO1 proteins was elevated,and the expression of Bcl-2 proteins was lowered in the three experimental groups.Moreover,the expression of related proteins showed more significant changes with the increase of magnet thickness(pressure).To conclude,skin compression activates PIEZO1,leading to a significant influx of calcium ions.As the pressure increases,this ultimately results in cell apoptosis due to calcium overload.

BACKGROUND:Currently,spinal endoscopic technology has become the mainstream technology in minimally invasive spinal surgery.The specifications of the instruments for different operating systems are different,and the choice of specific surgical protocols needs to be combined with the actual situation of the patient and the choice of the clinical surgeon. OBJECTIVE:To compare the early efficacy of percutaneous endoscopic interlaminar discectomy for L5-S1 disc herniation under the iLESSYS Delta System and Endo-Surgi Plus System. METHODS:Totally 80 patients with L5-S1 disc herniation were treated with percutaneous endoscopic interlaminar discectomy.Patients were divided into two groups based on the endoscopic system used.Among them,37 cases received the iLESSYS Delta System(Delta group)and 43 cases received the Endo-Surgi Plus System(Plus group).Patient demographic characteristics,perioperative indicators,and complications were analyzed between the two groups.Clinical outcomes were quantified using back and leg visual analog scale scores,Oswestry Disability Index,and Japanese Orthopaedic Association scores at 1 day,1,3,and 6 months after surgery.Patient satisfaction was assessed according to modified MacNab criteria at final follow-up. RESULTS AND CONCLUSION:(1)The operative time and number of arthroplasties in the Plus group were less than those in the Delta group,and the differences were statistically significant(P<0.05).(2)Compared with the preoperative period,the visual analog scale scores,Oswestry Disability Index,and Japanese Orthopaedic Association scores of patients in both groups improved at all follow-up time points,and the difference was statistically significant(P<0.001).(3)There was no statistically significant difference in the comparison of pain visual analog scale scores,Oswestry Disability Index,and Japanese Orthopaedic Association scores of patients in the two groups(P>0.05).(4)At 6-month follow-up after surgery,the MacNab standard excellent and good rates in the Delta group and Plus group were 81%and 79%,respectively,with no significant difference(P=0.823).(5)The incidence of complications was 3%in the Delta group and 2%in the Plus group,but there was no significant difference between the two groups(P=0.914).(6)It is concluded that both iLESSYS Delta and Endo-Surgi Plus surgical systems achieved satisfactory early clinical results in the treatment of lumbar disc herniation,with Endo-Surgi Plus surgical moulding being more efficient and safer.

ObjectiveTo explore the possible mechanism of Yigan Fupi Prescription （抑肝扶脾方， YFP） in treating diarrhea-type irritable bowel syndrome （IBS-D） by investigating the AKT/mTOR signaling pathway. MethodsSixty SD rats were randomly divided into control group， model group， YFP low-， medium-， and high-dose group， and pinaverium bromide group， with 10 rats in each group. All groups but the control group， were subjected to 21 days of tail-clamping stimulation and 14 days of senna leaf gavage to establish a liver stagnation and spleen deficiency-type IBS-D rat model. After successful modeling， the YFP low-， medium-， and high-dose group were administered 0.96， 1.93， and 3.87 g/（kg·d） of the prescription， respectively. The pinaverium bromide group was given 13.5 mg/（kg·d）， while the control and model groups were given 10 ml/（kg·d） distilled water. All groups were administered once daily for 14 consecutive days. General conditions of the rats were recorded during the experiment， and after modeling and drug administration， body weight， Bristol stool score， abdominal withdrawal reflex （AWR） score， and histo pathology of colon tissue were observed under HE staining. ELISA was used to detect serum levels of tumor necrosis factor α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Immunofluorescence was employed to detect the levels of AKT/mTOR pathway-related proteins including phosphorylated AKT （p-AKT）/AKT and phosphorylated mTOR （p-mTOR）/mTOR in the colon tissue. Western Blotting was used to detect the levels of autophagy-related proteins， including UNC-51-like kinase 1 （ULK1）， Beclin1 and LC3， and tight junction proteins including Occludin and ZO-1 in the colon tissue. ResultsAfter modeling， compared to the control group， the body weight of rats in the other groups decreased， and Bristol stool scores， as well as AWR scores under 20， 40， 60， and 80 mmHg increased （P＜0.05 or P＜0.01）. After drug administration， compared to the control group， the model group showed reduced body weight， decreased ULK1， Beclin1， LC3Ⅱ/LC3Ⅰ， Occludin， and ZO-1 protein levels in the colon tissue （P＜0.05 or P＜0.01）， and increased Bristol stool scores， AWR scores， serum TNF-α， IL-1β， and IL-6 levels， as well as p-AKT/AKT and p-mTOR/mTOR protein relative expression levels （P＜0.05 or P＜0.01）. Pathological results showed a significant reduction in goblet cells in the upper part of the glandular layer of the colon， with mild inflammatory cell infiltration. The submucosal collagen fibers were dissolved， with unclear boundaries， pale staining， and microvascular congestion and dilation. Compared with the model group， the YFP low-， medium-， and high-dose group and the pinaverium bromide group showed increased body weight， Beclin1， Occludin， and LC3Ⅱ/LC3Ⅰ protein levels （P＜0.05 or P＜0.01）， and decreased Bristol stool scores， AWR scores under 40， 60， and 80 mmHg， serum IL-1β， IL-6， TNF-α levels， and p-AKT/AKT， p-mTOR/mTOR protein relative expression levels （P＜0.05 or P＜0.01）. The pathological morphology of the rats in the YFP groups and pinaverium bromide group showed varying degrees of improvement. Compared with the pinaverium bromide group， the YFP low- and medium-dose group showed increased AWR scores under 20， 40， and 60 mmHg （P＜0.05）. The YFP low-dose group had reduced TNF-α， IL-1β， and IL-6 levels， and increased p-mTOR/mTOR protein relative expression levels occured in all YFP groups （P＜0.05）. Compared with the YFP low-dose group， the YFP high-dose group and pinaverium bromide group showed decreased AWR scores under different pressure levels and reduced p-AKT/AKT protein relative expression levels， while the YFP medium- and high-dose group had elevated serum TNF-α， IL-1β levels and reduced p-mTOR/mTOR protein relative expression levels （P＜0.05）. ConclusionYFP can effectively improve the pathological injury of colon tissue in IBS-D model rats with liver stagnation and spleen deficiency， reduce Bristol stool and AWR scores， and its mechanism may be related to reducing level of inflammatory factors and inhibiting AKT/mTOR pathway-related proteins in colon tissue， thereby enhancing the expression of autophagy-related proteins in the colon tissue.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

OBJECTIVE To assess the safety profile of sintilimab in combination with chemotherapy for the treatment of cholangiocarcinoma. METHODS The data of patients with cholangiocarcinoma from January 1st， 2021 to December 31st， 2022 were collected and divided into control group （29 cases） and observation group （18 cases） based on different medication regimens. Patients in the control group were treated with Gemcitabine hydrochloride for injection+Cisplatin for injection or Oxaliplatin for injection， the observation group was treated with Sintilimab injection based on the control group. Patients in each group underwent blood routine， liver and kidney function， biochemical and other examinations before and after each treatment cycle to observe the occurrence of adverse drug reactions. The correlation of adverse drug reactions with drugs was evaluated with Naranjo’s scale. RESULTS The correlation between blood toxicity and drug use was deemed “probable” in both groups； however， the observation group exhibited a significantly higher score， indicating a stronger correlation. In the control group， hepatotoxic reactions were classified as “suspicious” whereas in the observation group， they were categorized as “probable”. The correlation of gastrointestinal symptoms between the two groups was considered “possible”. Systemic symptoms， skin toxicity， musculoskeletal toxicity， endocrine toxicity and renal toxicity were all classified as having a “suspicious” correlation with drug use. The total incidence of blood toxicity in the observation group was significantly higher than control group （P＝0.014）. There was no statistically significant difference in the total incidences of hepatotoxic， gastrointestinal symptoms， systemic symptoms， skin toxicity， musculoskeletal toxicity， endocrine toxicity， renal toxicity， or the incidence of grade 3 or higher blood toxicity， hepatotoxic between the two groups （P＞0.05）. For the patients experiencing adverse drug reactions， the symptoms were alleviated following drug discontinuation or symptomatic supportive treatment. No fatalities occurred during the treatment period. CONCLUSIONS Sintilimab combined with chemotherapy may significantly increase the risk of blood toxicity in patients with cholangiocarcinoma， especially thrombocytopenia， but the adverse reactions are within a controllable range， and the overall safety is good.