Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Despite that sleep disturbance and poor neurocognitive performance are common complaints among coronavirus disease 2019 (COVID-19) survivors, few studies have focused on the effect of post-COVID-19 sleep disturbance (PCSD) on cognitive function. This study aimed to identify the impact of PCSD on neurocognitive function and explore the associated risk factors for the worsening of this condition. This cross-sectional study was conducted via the web-based assessment in Chinese mainland. Neurocognitive function was evaluated by the modified online Integrated Cognitive Assessment (ICA) and the Number Ordering Test (NOT). Propensity score matching (PSM) was utilized to match the confounding factors between individuals with and without PCSD. Univariate analyses were performed to evaluate the effect of PCSD on neurocognitive function. The risk factors associated with worsened neurocognitive performance in PCSD individuals were explored using binary logistic regression. A total of 8692 individuals with COVID-19 diagnosis were selected for this study. Nearly half (48.80%) of the COVID-19 survivors reported sleep disturbance. After matching by PSM, a total of 3977 pairs (7954 individuals in total) were obtained. Univariate analyses revealed that PCSD was related to worse ICA and NOT performance (P<0.05). Underlying disease, upper respiratory infection, loss of smell or taste, severe pneumonia, and self-reported cognitive complaints were associated with worsened neurocognitive performance among PCSD individuals (P<0.05). Furthermore, aging, ethnicity (minority), and lower education level were found to be independent risk factors for worsened neurocognitive performance in PCSD individuals (P<0.05). PCSD was related to impaired neurocognitive performance. Therefore, appropriate prevention and intervention measures should be taken to minimize or prevent PCSD and eliminate its potential adverse effect on neurocognitive function.
Humans ; COVID-19/epidemiology* ; Male ; Female ; Sleep Wake Disorders/epidemiology* ; Propensity Score ; Middle Aged ; Cross-Sectional Studies ; Adult ; SARS-CoV-2 ; Aged ; Risk Factors ; China/epidemiology* ; Cognition ; Cognitive Dysfunction/etiology* ; Neuropsychological Tests

Objective:To evaluate the efficacy of W-shaped excision of glabellar lines combined with botulinum toxin type A (BTX-A) injection for treating moderate to severe glabellar lines.Methods:A retrospective analysis was conducted on the clinical data of patients at the Department of Plastic and Cosmetic Surgery, the First Hospital of Jilin University, from June 2021 to June 2024. All the patients had noticeable dynamic and static glabellar lines—primarily featuring vertical, depressed wrinkles. All of them underwent W-shaped glabellar excision combined with BTX-A injection. All the depressed wrinkles were completely removed during the operation, followed by suturing the bilateral tissues towards the center to improve the underlying tissue depression. Immediately following surgery, 20 units of BTX-A were administered into the glabellar muscle complex using the standardized five-point injection technique. Patients were instructed to receive repeat BTX-A injections at regular intervals of 4 to 6 months. Postoperative assessments were conducted at 6 and 12 months to evaluated both surgical efficacy and patient-reported satisfaction. Surgical outcomes were assessed by three independent physicians who evaluated the severity of glabellar lines at rest using a four-grade scale (none, mild, moderate, or severe). The consensus rating was determined by majority agreement. Patient satisfaction was assessed using a three-point Likert-type scale, categorized as very satisfied, satisfied, or dissatisfied.Results:The study cohort comprised 37 patients (12 males and 25 females), aged between 29 and 59 years (mean age, 42.4 years). All patients exhibited moderate to severe glabellar lines characterized by vertical depressed wrinkles. All incisions achieved primary healing without hematoma, infection, or other complications. During a follow-up period of 12 to 24 months, with an average of 13.7 months, all patients presented various degrees of improvement in glabellar lines. At 6 months postoperatively, 54.1% (20/37) of patients exhibited no visible lines, 40.5% (15/37) had mild static lines, and 5.4% (2/37) had moderate static lines; no cases of severe static lines were observed. The overall patient satisfaction rate (very satisfied and satisfied) was 94.6% (35/37). At 12 months postoperatively, 95.2% (20/21) of patients in the regular injection group (≥2 injections) maintained a status of no or mild static lines, whereas 43.8% (7/16) of patients in the single-injection group developed moderate to severe static lines. The patient satisfaction survey showed that the proportion of patients reporting "very satisfied" or "satisfied" was 100% (21/21) in the regular injection group and 87.5% (14/16) in the single-injection group. No serious complications were observed throughout the follow-up period.Conclusion:The combination of W-shaped excision and BTX-A injection provides satisfactory clinical result for moderate to severe glabellar lines. Patients who adhere to a regimen of regular injections demonstrate longer-lasting surgical effects.

AIM To establish an HPLC method for the simultaneous content determination of 5-hydroxymethylfurfural,chlorogenic acid,caffeic acid,strychnine,paeoniflorin,ferulic acid,paeoniflorin Ⅰ,epimedium glycoside,psoralen,isopsoralen and glycyrrhetinic acid in Bunao Soft Capsules.METHODS The analysis was performed on a 35 ℃ thermostatic Waters Symmetry C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 230,280 nm.RESULTS Eleven constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 98.47％-103.30％with RSDs of 1.13％-2.80％.CONCLUSION This simple and reliable method can be used for the quality control of Bunao Soft Capsules.

OBJECTIVE To evaluate the quality of Euscaphis japonica from different habitats. METHODS The relative correction factors of gallic acid， protocatechuic acid， ellagic acid， isoquercitrin， astragalin and apigenin were calculated with quercetin as the internal reference； the relative correction factors of euscaphic acid， oleanolic acid， stigmasterol and β-sitosterol were also calculated with ursolic acid as the internal reference. The contents of 12 components in 18 batches of samples were calculated by QAMS method and were compared with external standard method. At the same time， the contents of water-soluble extract， alcohol-soluble extract， total ash and acid-insoluble ash were detected. The quality of E. japonica was evaluated by principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA）， and weighted technique for order preference by similarity to ideal solution （TOPSIS） method. RESULTS There was no significant difference between the results of QAMS method and external standard method for the 12 components in the 18 batches of samples. However， notable content variations were observed among different batches of samples. The results of PCA and OPLS-DA showed that S1-S7， S8- S12， and S13-S18 were clustered into one category respectively. Seven key characteristic components variable importance in projection values ＞1， euscaphic acid， ursolic acid， protocatechuic acid， apigenin， β-sitosterol， isoquercitrin， and oleanolic acid， respectively. The analysis results of the weighted TOPSIS method revealed that the relative closeness for evaluating the quality of 18 batches of samples ranged from 0.283 5 to 0.644 1， with the samples of E. japonica from Fengjie， Chongqing， demonstrating the highest quality. CONCLUSIONS The established method is accurate and feasible， which can be used for the quality evaluation of E. japonica combined with chemometrics and weighted TOPSIS model.

Objective To investigate the role of Yes-associated protein(YAP)in bone resorption exac-erbated by occlusal trauma during periodontitis and its molecular mechanisms,and to evaluate the interven-tional effect of YAP inhibition on alveolar bone destruction.Methods Osteoclasts were stimulated by in vitro mechanical loading combined with lipopolysaccharide(LPS)to simulate the in vitro synergistic effect of occlu-sal stress and inflammation.A murine periodontitis model with occlusal trauma was established.Flow cytome-try,Western blot,qPCR,and immunofluorescence staining were employed to analyze YAP dephosphorylation and nuclear translocation in cellular and animal models,and to investigate YAP's regulatory effect on the c-Jun N-terminal kinase(JNK)/receptor activator of nuclear factor kappa-B ligand(RANKL)pathway.The YAP inhibitor XAV939 was administered to evaluate its impact on osteoclast activation and bone resorption through pathway intervention.Results In vitro,combined mechanical stress and LPS stimulation significantly reduced YAP phosphorylation in osteoclasts,promoted YAP nuclear translocation,and activated the JNK-RANKL pathway.In vivo,the periodontitis with occlusal trauma group exhibited markedly elevated expres-sion of YAP,JNK,and RANKL compared to the periodontitis-alone group(P<0.001).XAV939 intervention reversed YAP nuclear translocation,suppressed JNK phosphorylation and RANKL expression(P<0.01),and reduced osteoclast numbers.Conclusion YAP acts as a central hub integrating mechanical and inflammatory signals,exacerbating osteoclast differentiation and bone resorption via activation of the JNK-RANKL axis.Targeted inhibition of YAP effectively blocks this pathological cascade,offering a new approach for the precise treatment of periodontitis complicated by occlusal trauma.

Under the background of forensic medicine becoming a first-level discipline,the opportuni-ties and challenges of discipline development coexist.Starting from the actual situation and characteris-tics of local medical colleges and universities,this paper discusses the problems and solutions for the development of forensic medicine discipline from the perspective of building a regional high-level medical university.Combined with the experiences of carrying out forensic medicine education in our college,this paper supplies our thoughts and practices on improving the discipline system,enhancing the ability to serve society,perfecting the talent cultivation model and promoting forensic culture,to provide reference and inspiration for the development of forensic medicine in other universities,jointly promote the advancement of forensic medicine in China to a new stage,and contribute the wisdom and strength of forensic medical experts to the construction of a law-based China,a safe China and a healthy China.

Objective To evaluate"sequential theory"combined with"clinical simulation"method in teaching ultrasound-guided musculoskeletal intervention therapy.Methods Thirty-four students who participated in the"Musculoskeletal Ultrasound and New Technology Excellent Class"organized by the Department of Ultrasound Medicine of Peking University Third Hospital from November 20 to November 24,2023 were selected as the study objects.After"sequential theory"and"clinical simulation"training,the trainees joined theoretical exami-nation,ultrasound operation and model puncture examination,then a questionnaire survey was carried out.Results The theoretical and practical test scores of 34 students were all qualified,and there was no statistical difference in theoretical and practical test results among students with different educational backgrounds,profes-sional titles and whether they came from basic hospitals.The questionnaire showed that the students were satisfied with the content of the class.Conclusions The application of"sequential theory"and"clinical simulation"methods improves training outcomes of musculoskeletal ultrasound interventional therapy and shortens the learning curve of students.

ObjectiveTo establish the quality standards for Sennae Folium（Cassia angustifolia） dispensing granules based on standard decoctions. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established for 15 batches of Sennae Folium（C. angustifolia） standard decoctions and 10 of Sennae Folium（C. angustifolia） dispensing granules from different manufacturers， and the similarity evaluation， hierarchical cluster analysis（HCA） and principal component analysis（PCA） were performed. Linear calibration with two reference substances（LCTRS） and quantitative analysis of multi-components by single-marker（QAMS） were established for the common peaks in the specific chromatograms to determine the contents of main components in the decoction pieces， standard decoctions and dispensing granules， and to calculate their transfer rates from decoction pieces to standard decoctions and dispensing granules. ResultsThe similarities of specific chromatograms of 15 batches of Sennae Folium（C. angustifolia） standard decoctions and 10 batches of Sennae Folium（C. angustifolia） dispensing granules were all greater than 0.95， and a total of 8 characteristic peaks were calibrated， and five of them were identified， including kaempferol-3，7-O-diglucoside， apigenin-6，8-di-C-glucoside， quercetin-3-O-gentianoside， sennoside B and sennoside A. HCA and PCA results showed that there were certain differences in the composition of different batches of standard decoctions， but no clustering was observed in the production area. As the standard decoctions， the extract rate of 15 batches of samples was 26.54%-45.38%， the contents of kaempferol-3，7-O-diglucoside， apigenin-6，8-di-C-glucoside， quercetin-3-O-gentianoside， sennoside B and sennoside A were 12.16-19.26， 2.57-4.94， 3.27-5.11， 6.75-11.39， 4.69-7.79 mg·g^-1， and their transfer rates from decoction pieces to standard decoctions were 45.41%-79.02%， 29.12%-55.07%， 40.52%-67.90%， 24.72%-49.12%， 27.54%-49.34%， respectively. The extract rates of Sennae Folium（C. angustifolia） dispensing granules（C8-C10） were 38.10%-39.50%， the transfer rates of the above five components from decoction pieces to dispensing granules were 72.85%-73.58%， 53.43%-53.94%， 40.19%-40.74%， 24.62%-25.00%， 28.65%-29.11%， respectively， which were generally consistent with the transfer rates from decoction pieces to standard decoctions. ConclusionCompared with the relative retention time method， LCTRS has higher prediction accuracy and is more suitable for chromatographic columns. The established quality control standard of Sennae Folium（C. angustifolia） dispensing granules based on standard decoction is reasonable and reliable， and all indicators of samples from different manufacturers are within the range specified based on the standard decoction， which can provide reference for the quality control and process research of this dispensing granules.