ObjectiveTo make clear exercise combined with Shenghui Tang interferes in acetylcholine receptor （M1AChR） to improve mitochondrial autophagy and enhance cognition of Alzheimer's disease （AD） model rats through the adenylate activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsForty-eight male SD rats of SPF grade were randomly divided into a blank group， a model group， a Shenghui Tang group （9.3 g·kg^-1）， an exercise group， an exercise + Shenghui Tang group （9.3 g·kg^-1）， and a rapamycin group （1.5 mg·kg^-1）. Except for the blank group， the rat model of AD was constructed by injecting amyloid beta （Aβ_1-42） into hippocampus stereotaxically. The exercise group received treadmill exercise for 4 weeks， while the Shenghui Tang group received intragastric administration for 4 weeks， and the exercise + Shenghui Tang group received treadmill exercise and intragastric administration of Shenghui Tang for 4 weeks simultaneously. After the intervention， the Morris water maze test was used to detect the learning and memory ability. Spontaneous behavior was observed in the open field test. The pathological structure of hippocampal neurons was observed by NISSl staining. The expression level of M1AChR in hippocampus was detected by immunohistochemistry （IHC）. The autophagy ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The apoptosis rate was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）. The expression of Beclin1 and microtubule-associated protein light chain 3β （LC3β） was detected by immunofluorescence （IF）. The protein expression of M1AChR， AMPK， p-AMPK， mTOR， Beclin1， LC3β， and chelate 1 （SQSTM1/p62） in hippocampus was detected by Western blot. ResultsCompared with the blank group， the model group exhibited significantly increased platform escape latency on the fifth day （P<0.01） and significantly decreased activity distance in the target quadrant and times of crossing the platform （P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed obviously decreased （P<0.05）. The arrangement of nerve cells in hippocampus CA1 region was dispersed， and the numbers of Nissl bodies and M1AChR positive cells significantly decreased （P<0.01）. The expression of TUNEL positive cells was significantly increased （P<0.01）. The typical autophagic lysosomal structure decreased. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， Beclin1， LC3Ⅱ/Ⅰ in hippocampus was significantly decreased （P<0.01）， and the protein expression of p62 was significantly increased （P<0.01）. Compared with the model group， the exercise + Shenghui Tang group exhibited obviously improved space exploration and positioning navigation ability （P<0.05， P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed of movement significantly increased （P<0.01）. The number of Nissl bodies significantly increased （P<0.01）. The number of M1AChR positive cells in hippocampus was significantly increased （P<0.01）. The expression of TUNEL positive cells was significantly decreased （P<0.01）. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， Beclin1， LC3Ⅱ/Ⅰ in hippocampus was significantly increased （P<0.01）， while the protein expression of p62 was significantly decreased （P<0.01）. Compared with the exercise + Shenghui Tang group， the Shenghui Tang group and the exercise group showed significantly increased platform escape latency on the fifth day （P<0.01） and obviously decreased activity distance in the target quadrant and times of crossing the platform （P<0.05， P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed of movement significantly decreased （P<0.01）. The number of Nissl bodies and the number of M1AChR positive cells significantly decreased （P<0.01）. The expression of TUNEL positive cells was obviously increased （P<0.05）. Ultrastructure of the hippocampal region showed decreased autophagy level. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， LC3Ⅱ/Ⅰ in the hippocampus was obviously decreased in the Shenghui Tang group （P<0.05， P<0.01）， while the protein expression of p62 was significantly increased （P<0.01）. In the exercise group， the protein expression of M1AChR， p-AMPK/AMPK， Beclin1， and LC3Ⅱ/Ⅰ was obviously decreased （P<0.05， P<0.01）， while the protein expression of p-mTOR/mTOR and p62 was significantly increased （P<0.01）. ConclusionExercise combined with traditional Chinese medicine can enhance the expression of M1AChR in the hippocampus of AD model rats， induce autophagy through the AMPK/mTOR signaling pathway， and improve the learning and memory ability of AD rats.

Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

Objective To investigate the capacity of municipal and county-level Centers for Disease Control (CDC) in Shandong Province for γ radionuclides in food as well as gross α and gross β in drinking water, and to provide evidence for strengthening radiological laboratories. Method Data regarding radioactive detection capacity were collected from 16 prefecture-level cities and 136 county-level CDCs. Chi-square test and Fisher's exact tests were used to compare capacity differences across regions and between cities with and without nuclear power plants. Correlation analysis was used to evaluate the spatial equity of gross α and gross β detection capacity for drinking water. Result The detection capacity of gross α and gross β in drinking water varied significantly among counties (χ²=81.026, P<0.001），no significant difference was found between coastal and inland cities (χ²=2.021，P>0.155); Cities with nuclear power plants showed better detection capacity (χ²=20.253，P<0.01). The detection capacity for γ radionuclides in food was primarily concentrated in the prefecture-level cities that host nuclear power plants. Conclusion The overall detection capacity for radioactivity in drinking water was acceptable but spatially uneven. The capacity for monitoring radioactive contamination in food was generally weak. It is necessary to strengthen capacity building at the grassroots level.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

ObjectiveThe rapid advancement of bioanalytical technologies has heightened the demand for high-throughput, label-free, and real-time cellular analysis. Electrochemical impedance spectroscopy (EIS) operating in the GHz frequency range (GHz-EIS) has emerged as a promising tool for characterizing cell suspensions due to its ability to rapidly and non-invasively capture the dielectric properties of cells and their microenvironment. Although GHz-EIS enables rapid and label-free detection of cell suspensions, significant challenges remain in interpreting GHz impedance data for complex samples, limiting the broader application of this technique in cellular research. To address these challenges, this study presents a novel method that integrates GHz-EIS with deep learning algorithms, aiming to improve the precision of cell suspension concentration identification and quantification. This method provides a more efficient and accurate solution for the analysis of GHz impedance data. MethodsThe proposed method comprises two key components: dielectric property dataset construction and backpropagation (BP) neural network modeling. Yeast cell suspensions at varying concentrations were prepared and separately introduced into a coaxial sensor for impedance measurement. The dielectric properties of these suspensions were extracted using a GHz-EIS dielectric property extraction method applied to the measured impedance data. A dielectric properties dataset incorporating concentration labels was subsequently established and divided into training and testing subsets. A BP neural network model employing specific activation functions (ReLU and Leaky ReLU) was then designed. The model was trained and tested using the constructed dataset, and optimal model parameters were obtained through this process. This BP neural network enables automated extraction and analytical processing of dielectric properties, facilitating precise recognition of cell suspension concentrations through data-driven training. ResultsThrough comparative analysis with conventional centrifugal methods, the recognized concentration values of cell suspensions showed high consistency, with relative errors consistently below 5%. Notably, high-concentration samples exhibited even smaller deviations, further validating the precision and reliability of the proposed methodology. To benchmark the recognition performance against different algorithms, two typical approaches—support vector machines (SVM) and K-nearest neighbor (KNN)—were selected for comparison. The proposed method demonstrated superior performance in quantifying cell concentrations. Specifically, the BP neural network achieved a mean absolute percentage error (MAPE) of 2.06% and an R² value of 0.997 across the entire concentration range, demonstrating both high predictive accuracy and excellent model fit. ConclusionThis study demonstrates that the proposed method enables accurate and rapid determination of unknown sample concentrations. By combining GHz-EIS with BP neural network algorithms, efficient identification of cell concentrations is achieved, laying the foundation for the development of a convenient online cell analysis platform and showing significant application prospects. Compared to typical recognition approaches, the proposed method exhibits superior capabilities in recognizing cell suspension concentrations. Furthermore, this methodology not only accelerates research in cell biology and precision medicine but also paves the way for future EIS biosensors capable of intelligent, adaptive analysis in dynamic biological research.

The 2024 National Education Work Conference pointed out that at the current juncture of the critical period for achieving the goals and tasks of the 14th Five-Year Plan,the implementation of the Education Powerhouse Construction Plan Outline should be taken as the main line of work,and building first-class disciplines is an crucial task for a higher education powerhouse.In 2022,forensic medicine was officially listed as a first-level discipline under the medical category,presenting an un-precedented historical opportunity for the development of forensic medicine.The forensic medicine dis-cipline of Southern Medical University comprehensively improves the quality of talent cultivation and facilitates the construction of first-class disciplines as its main direction.It aims to initiate and imple-ment a high-level faculty team building plan featuring"combining recruitment and cultivation,inter-disciplinary integration";make vigorous efforts to establish a first-level doctoral program,refine advan-tageous second-level disciplines and research directions;and establish an innovative research platform from a high starting point with deep integration.The discipline adheres to moral cultivation and the Five Domains of Education simultaneous development,to build a high-quality talent joint training model.Guided by the construction of the national legal system and industry needs,the discipline will enhance social service capabilities.The forensic medicine construction in our university will continue to contribute to the rule of law in China and educational power.

With advancements in in vitro culture techniques, the morula has emerged as a promising candidate for selective embryo transfer due to its critical compaction phase. The compaction process involves not only structural reorganization but also complex intercellular signaling mechanisms that significantly influence embryonic developmental potential and cellular fate determination. Clinical data reveal comparable live birth rates between day 4 morula transfers and day 5 blastocyst transfers, coupled with reduced in vitro culture duration. However, challenges persist regarding standardized evaluation criteria and long-term safety confirmation. Current morphological assessment methods exhibit inherent subjectivity, while emerging technologies integrating genetic screening, metabolic analysis, and time-lapse imaging show potential for enhanced selection accuracy. Personalized synchronization assessments, including endometrial receptivity analysis, may further optimize transfer protocols. This study focuses on day 4 embryo transfer, systematically reviewing its embryonic development processes, evaluation protocols, comparative outcomes of transferred embryos, and research advances in frozen-thawed embryo transfer. The study aims to deepen scientific understanding of day 4 embryo transfer and promote its adoption as a critical option in personalized reproductive medicine, thereby enhancing clinical success rates and safety.

Objective:To establish a day 4 embryo evaluation protocol by analyzing embryonic characteristics affecting blastocyst formation, and validate its clinical effectiveness.Methods:This retrospective cohort study included clinical data from 1 037 patients who underwent fresh in vitro fertilization and embryo transfer (IVF-ET) on day 4 in Center for Reproductive Medicine of Xingtai Meihe Reproductive and Genetic Hospital between January 2018 and April 2024. Morphological assessments were performed at (92±2) h post-fertilization. After excluding 1 326 embryos selected for fresh transfer, 2 723 embryos underwent blastocyst culture. To address selection bias in transferred embryos, the scoring system was primarily based on high-quality blastocyst formation rates. Multivariate binary regression analysis evaluated how day 4 developmental stage, fragmentation rate, stage-specific cleavage patterns, multinucleation/vacuolization affected transferable blastocyst formation rate and high-quality blastocyst rate. Regression coefficients determined parameter weights for high-quality blastocyst formation, establishing a day 4 embryo scoring protocol that compared outcomes across different grades. The scoring system was validated by comparing transferable blastocyst formation rate, high-quality blastocyst rate, and implantation rate among different day 4 embryo grades. All embryos were further rescored according to three previously reported evaluation schemes [Feil 2008, Gemma 2015, and European Society of Human Reproduction and Embryology (ESHRE) 2011]. The predictive values of these three day 4 scoring systems and the day 4 scoring system established in this study were compared using the area under the curve (AUC) receiver operating characteristic (ROC) curve in predicting the formation rate of transferable blastocyst, the formation rate of high-quality blastocyst, and implantation rate. Results:In the prediction of high-quality blastocyst formation, early blastocyst showed the highest influence weight compared to embryos with the ratio of blastomere numbers on day 4 to those on day 3 (BNR) <1.2 ( B=3.398, OR=29.915, P<0.001), followed by fragmentation <10% versus ≥50% ( B=1.263, OR=3.535, P<0.001), a stage-specific cleavage pattern ( B=0.903, OR=2.467, P=0.005), and absence of multinucleation or vacuoles ( B=0.797, OR=2.218, P=0.007). Using the newly developed day 4 scoring system, embryos were graded A, B, C, D, E. Transferable blastocyst formation rates were 88.57% (279/315), 76.99% (241/313), 56.11% (280/499), 40.27% (238/591) and 14.22% (143/1 005), respectively; high-quality blastocyst rates were 51.42% (162/315), 35.46% (111/313), 20.04% (100/499), 9.47% (56/591) and 3.98% (40/1 005). All inter-group differences were statistically significant (all P<0.005). Implantation rates for transferred embryos of grades A-E declined sequentially: 63.18% (381/603), 56.19% (322/573), 38.29% (54/141), 26.53% (13/49) and 9.67% (3/31). The day 4 embryo scoring system proposed in this study demonstrated significantly higher predictive efficacy for transferable blastocyst formation rate (AUC=0.812), high-quality blastocyst formation rate (AUC=0.804), and implantation rate (AUC=0.603) compared with Feil 2008 (AUC=0.797, P<0.001; AUC=0.781, P<0.001; AUC=0.585, P<0.001), Gemma 2015 (AUC=0.773, P<0.001; AUC=0.771, P<0.001; AUC=0.542, P=0.006), and ESHRE 2011 (AUC=0.710, P<0.001; AUC=0.745, P<0.001; AUC=0.592, P<0.001). We also observed the presence of pseudo-compacted embryo, whose transferable blastocyst formation rate [38.28% (49/128)] and high-quality blastocyst formation rate [7.03% (9/128)] were similar to those of cleavage-stage embryos with a BNR≥1.2. Conclusion:The established day 4 morphological assessment system reliably predicts the potential to transferable blastocyst and high-quality blastocyst, and effectively forecasts implantation rates.

Objective To investigate the expression pattern of IQGAP2 in renal cell carcinoma tissues and cell lines,and to analyze its effects on the proliferation and migration of renal cell carcinoma cells.Methods Firstly,GEO database was used to screen differentially expressed genes between renal cell carcinoma tissues,and GEPIA,TIMER2.0 were used to analyze the expression level of IQGAP2 in renal cell carcinoma tissue.Subse-quently,knockdown(siRNA)and overexpression plasmids of IQGAP2 were constructed and transfected into ACHN and 786-O cell lines to perform a series of functional experiments to evaluate the effect of IQGAP2 on the malignant biological behavior of renal carcinoma cells.qRT-PCR and Western Blot were used to detect the expres-sion of EMT(epithelial-mesenchymal transition)related proteins after knockdown and overexpression of IQGAP2.Results In renal cell carcinoma tissues,the relative expression of IQGAP2 was significantly lower than in adja-cent normal tissues(P<0.001).Transfection of si-IQGAP2 in ACHN and 786-O cells effectively downregulated the mRNA and protein expression levels of IQGAP2(P<0.01),while transfection with an overexpression plasmid significantly upregulated its mRNA and protein expression(P<0.001).Further studies revealed that overexpression of IQGAP2 significantly inhibited the proliferation(P<0.05)and migration(P<0.01)of ACHN and 786-O cells,whereas knockdown of IQGAP2 enhanced their proliferation(P<0.05,P<0.001)and migration(P<0.01).Through qRT-PCR and Western blot analyses of EMT-related proteins,it was found that reduced expression of IQGAP2 promoted the epithelial-mesenchymal transition(EMT)process in renal cancer cells.Conclusions The expression of IQGAP2 is low in renal cell carcinoma tissues and cells,and the decrease of the expression level can promote the EMT process of renal cell carcinoma cells,and then enhance the proliferation and migration of renal cell carcinoma cells.IQGAP2 plays an important tumor suppressor role in renal cell carcinoma.

Objective·To compare the safety and short-term outcomes of robot-assisted versus laparoscopic-assisted proximal gastrectomy combined with double-flap esophagogastrostomy in the treatment of early upper gastric cancer.Methods·A retrospective cohort study was conducted to analyze the clinical and pathological data of 31 early gastric cancer patients who underwent proximal gastrectomy combined with double-flap esophagogastrostomy for gastrointestinal reconstruction at the Department of Gastrointestinal Surgery,Renji Hospital,Shanghai Jiao Tong University School of Medicine,from September 2023 to March 2024.Based on the surgical approach,patients were divided into the robot-assisted surgery group(robotic group,20 cases)and the laparoscope-assisted surgery group(laparoscopic group,11 cases).General clinical data,intraoperative conditions,and postoperative recovery between the two groups were compared.At the 6-month postoperative follow-up,upper gastrointestinal radiography and esophagogastroscopy were performed to assess anastomotic stricture and gastroesophageal reflux disease.Additionally,the gastric cancer-specific module of the European Organization for Research and Treatment of Cancer(EORTC),Quality of Life Questionnaire-Stomach 22(QLQ-STO22),was used to evaluate the patients' quality of life.Results·The general data of the two groups,including gender,age,preoperative comorbidities,American Society of Anesthesiologists(ASA)classification,Siewert classification,and pathological staging of tumors,showed no statistically significant differences(all P>0.05).All patients successfully underwent the procedure without conversion to open surgery.The time for gastroesophageal anastomosis was significantly shorter in the robotic group compared to the laparoscopic group[(31.09±8.23)min vs(43.73±8.83)min,P<0.001],while there were no statistically significant differences in other intraoperative and postoperative parameters,including operative time,intraoperative blood loss,number of lymph nodes removed,duration of gastric tube placement,time to start a liquid diet,length of postoperative hospital stay,and incidence of postoperative complications(all P>0.05).At the 6-month postoperative follow-up,30 patients completed the follow-up,with one patient lost to follow-up in the robotic group.Upper gastrointestinal radiography and esophagogastroscopy results showed that only one patient in the laparoscopic group developed an anastomotic stricture,while one patient in the robotic group developed grade A and one developed grade B gastroesophageal reflux disease(GERD).In addition,one patient in the laparoscopic group also developed grade B GERD.The incidences of GERD and anastomotic stricture showed no statistically significant differences between the two groups(both P>0.05).EORTC QLQ-STO22 results indicated that the robotic group had significantly lower scores in the dimensions of dysphagia,gastroesophageal reflux,and dietary restrictions,as well as in the total score,compared to the laparoscopic group(all P<0.05).Conclusion·Robot-assisted proximal gastrectomy combined with double-flap esophagogastrostomy is safe and feasible.It shortens anastomosis time and offers potential advantages in postoperative functional recovery and quality of life improvement.