Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

By reviewing the physical biological research on the activation of acupoint effects by acupuncture， this paper explains the activation mechanism from the perspective of the generation and transmission of mechanical signals caused by acupuncture， and reveals the physical-chemical coupling processes in the acupoint microenvironment. Future research should focus on locally mechanosensitive cells， further exploring how acupuncture mechanical signals trigger dynamic changes in cells and molecules in the acupoints， and the physical-chemical information transduction mechanism， which will provide scientific evidence for the acupoint activation during acupuncture. Related studies will contribute to a deeper understanding of the scientific principles behind acupuncture and promote its clinical application and development.

Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

With the rapid advancement of vaccines, the research and application of vaccine adjuvants have garnered significant attention. Despite the development of numerous vaccine adjuvants, their applications in human vaccines remain limited due to either insufficient efficacy or severe side effects. Consequently, there is growing interest in developing bioactive compounds derived from traditional Chinese medicines (TCMs) as vaccine adjuvants, owing to their natural biocompatibility, diversity, and safety. Here, we systematically review the current application status and potential value of TCM-based bioactive compounds in vaccine adjuvants. Firstly, we elaborate on the types and characteristics of active ingredients, such as polysaccharides, saponins, flavonoids, acids, and alkaloids. The mechanisms by which these compounds function as vaccine adjuvants are then discussed, including their roles in enhancing humoral immunity, cellular immunity, and relieving the immune suppression in the microenvironment. Additionally, we summarize the current strategies for structural modification and platform optimization to adapt to different application scenarios. Finally, we offer insights into the future development directions for these potential adjuvants, highlighting research priorities, technical approaches, and application prospects. In conclusion, natural vaccine adjuvants derived from TCMs present broad application prospects and hold promise for future vaccine development.

METHODS: Cardiac organoids derived from the self-assembled human induced pluripotent stem cells were constructed by regulating the Wnt signaling pathway. Flow cytometry was used to detect the proportion of cardiomyocytes in the cardiac organoids, and RT-qPCR was employed to detect the mRNA expressions. Immunofluorescence staining was used to detect the protein expressions of TNNT2, CD31, and vimentin. The beating amplitude of the cardiac organoids was determined with calcium transient. In vitro myocardial injury models and ischemia-reperfusion models were established, and the cell injuries were examined using Masson staining. TUNEL staining and calcium transient detection were used to evaluate the adverse effects of doxorubicin and trastuzumab in the cardiac organoids. RESULTS: The cardiac organoids began to beat on the 8th day of culture and consisted of 32.4% cardiomyocytes with high expressions of the myocardial markers TNNT2, NKX2.5, RYR2 and KCNJ2. No significant differences in morphological size, beating frequency, proportion of cardiomyocytes, or myocardial contractility were observed in the cardiac organoids differentiated from different batches. These cardiac organoids could be maintained in in vitro culture conditions for at least 50 days. Captopril treatment could obviously alleviate liquid nitrogen-induced myocardial injury in the cardiac organoids. Hypoxia/reoxygenation induced ischemia-reperfusion injury and promoted myocardial fibrosis and apoptosis in the cardiac organoids. Treatment with doxorubicin for 24 h resulted in significantly increased cell death and reduced beating frequency and cell viability in the cardiac organoids in a dose-dependent manner. Trastuzumab significantly impaired the contractile and calcium handling abilities of the cardiac organoids. CONCLUSIONS Cardiac organoids derived from human induced pluripotent stem cells have been successfully constructed and can be used for cardiac disease modeling and drug evaluation.
Humans ; Induced Pluripotent Stem Cells/cytology* ; Organoids/cytology* ; Myocytes, Cardiac/cytology* ; Cell Differentiation ; Heart Diseases

Objective:To develop a clinical automated diagnostic system for temporomandibular disor-ders(TMD)based on the diagnostic criteria for TMD(DC/TMD)to assist dentists in making rapid and accurate clinical diagnosis of TMD.Methods:Clinical and imaging data of 354 patients,who visited the Center for TMD & Orofacial Pain at Peking University Hospital of Stomatology from September 2023 to January 2024,were retrospectively collected.The study developed a clinical automated diagnostic system for TMD using the DC/TMD,built on the.NET Framework platform with branching statements as its in-ternal structure.Further validation of the system on consistency and diagnostic efficacy compared with DC/TMD were also explored.Diagnostic efficacy of the TMD clinical automated diagnostic system for de-generative joint diseases,disc displacement with reduction,disc displacements without reduction with limited mouth opening and disc displacement without reduction without limited mouth opening was evalua-ted and compared with a specialist in the field of TMD.Accuracy,precision,specificity and the Kappa value were assessed between the TMD clinical automated diagnostic system and the specialist.Results:Diagnoses for various TMD subtypes,including pain-related TMD(arthralgia,myalgia,headache attribu-ted to TMD)and intra-articular TMD(disc displacement with reduction,disc displacement with reduc-tion with intermittent locking,disc displacement without reduction with limited opening,disc displace-ment without reduction without limited opening,degenerative joint disease and subluxation),using the TMD clinical automated diagnostic system were completely identical to those obtained by the TMD spe-cialist based on DC/TMD.Both the system and the expert showed low sensitivity for diagnosing degenera-tive joint disease(0.24 and 0.37,respectively),but high specificity(0.96).Both methods achieved high accuracy(＞0.9)for diagnosing disc displacements with reduction and disc displacements without reduction with limited mouth opening.The sensitivity for diagnosing disc displacement without reduction without limited mouth opening was only 0.59 using the automated system,lower than the expert(0.87),while both had high specificity(0.92).The Kappa values for most TMD subtypes were close to 1,ex-cept the disc displacement without reduction without limited mouth opening,which had a Kappa value of 0.68.Conclusion:This study developed and validated a reliable clinical automated diagnostic system for TMD based on DC/TMD.The system is designed to facilitate the rapid and accurate diagnosis and classi-fication of TMD,and is expected to be an important tool in clinical scenarios.

Objective To investigate the effect of body mass index(BMI)on the clinicopathological characteristics of patients with idiopathic membranous nephropathy(IMN).Methods A total of 261 patients with IMN were divided into the normal group(66 cases),the overweight group(105 cases)and the obese group(90 cases)according to BMI.Clinical and renal pathological data of patients were compared between the three groups.The correlation between BMI and clinicopathological indexes was analyzed by Pearson or Spearman's correlation.The influencing factors of estimated glomerular filtration rate(eGFR)were analyzed by multiple linear regression,and the influencing factors of interstitial fibrosis(IF),tubular atrophy(TA),glomerulosclerosis(GS)and mesangial cell proliferation(MCP)were analyzed by binary Logistic regression.Results Compared with the normal group,the prevalence of diabetes mellitus,triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)were elevated in the overweight group.The prevalence of hypertension,hemoglobin(HGB),uric acid(UA),LDL-C,TG,24-h urinary protein(UTP)and serum complement 3(C3)were elevated,and high-density lipoprotein cholesterol(HDL-C)was decreased in the obese group(P＜0.05).The prevalence of hypertension,UA,TG and serum C3 were elevated in the obese group compared to the overweight group(P＜0.05).The glomerular basement membrane(GBM)thickness was higher in the obese group and the overweight group than that in the normal group,and the proportion of GS and IF was higher in the obese group than that in the normal group(P＜0.05).BMI was positively correlated with hypertension,TG,LDL-C,serum C3,UTP,GS,IF,MCP and deposition in the mesangial region of C3,and negatively correlated with HDL-C(P＜0.05).Multiple linear regression analysis showed that age,blood urea nitrogen(BUN),anti-phospholipase A2 receptor antibody(anti-PLA2R),UTP and TA were independent risk factors of eGFR.Binary Logistic regression analysis showed that elevated BMI,age,UTP and serum creatinine(Scr)were independent risk factors for IF.Age,Scr and elevated UA were independent risk factors for TA.Elevated BMI and decreased eGFR were independent risk factors for GS.Elevated BMI was an independent risk factor for MCP.There was no significant difference in the treatment protocol of IMN patients between the three groups.Conclusion Obesity can exacerbate multiple clinical and pathological outcomes in IMN patients.

To explore the effects of plasma jet (PJ) and plasma activated water (PAW) on the sterilization of Streptococcus mutans ( S. mutans) and compare the advantages and disadvantages of the two methods, so as to provide a basis for plasma treatment of dental caries and to enrich the treatment means of dental caries, an atmospheric pressure plasma excitation system was built, and the effects of PJ and PAW on the sterilization rate of S. mutans and the changes of temperature and pH during treatment were studied under different excitation voltage ( U _e ) and different excitation time ( t _e ). The results showed that in the PJ treatment, the difference in the survival rate of S. mutans between the treatment group and the control group was statistically significant ( P = 0.007, d=2.66) when U _e = 7 kV and t _e = 60 s, and complete sterilization was achieved at U _e = 8 kV and t _e = 120 s in the PJ treatment. In contrast, in the PAW treatment, the difference in the survival rate of S. mutans between the treatment group and the control group was statistically significant ( P = 0.029, d = 1.71) when U _e = 7 kV and t _e = 30 s, and complete sterilization was achieved with PAW treatment when U _e = 9 kV and t _e = 60 s. Results of the monitoring of temperature and pH showed that the maximum temperature rise during PJ and PAW treatment did not exceed 4.3 °C, while the pH value after PAW treatment would drop to a minimum of 3.02. In summary, the optimal sterilization parameters for PJ were U _e =8 kV and 90 s < t _e ≤ 120 s, while the optimal sterilization parameters for PAW were U _e = 9 kV and 30 s< t _e ≤ 60 s. Both treatment methods achieved non-thermal sterilization of S. mutans, where PJ required only a smaller U _e to achieve complete sterilization, while at pH < 4.7, PAW only required a shorter t _e to achieve complete sterilization, but its acidic environment could cause some chemical damage to the teeth. This study can provide some reference value for plasma treatment of dental caries.
Humans ; Streptococcus mutans ; Dental Caries/therapy* ; Sterilization ; Temperature ; Water

BACKGROUND: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. METHODS: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. RESULTS: The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy. CONCLUSIONS The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
Humans ; Mendelian Randomization Analysis ; Irritable Bowel Syndrome ; Colorectal Neoplasms/genetics* ; Cholelithiasis/complications* ; Cholecystectomy/adverse effects* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Objective:To evaluate the medium-term clinical and hemodynamic outcomes of percutaneous pulmonary valve implantation (PPVI) using a domestic Venus-P self-expanding valve in the treatment of severe pulmonary regurgitation after Tetralogy of Fallot (TOF).Methods:Retrospective study.From December 2017 to December 2020, 13 TOF patients with (17.8±4.7) years old and (50.2±12.3) kg underwent PPVI using the Venus-P self-expanding valve in the Department of Children′s Heart Center, Zhengzhou University People′s Hospital were recruited.The mean valve size was (31.9±3.1) mm.All patients received the transannular patch surgery and developed severe pulmonary regurgitation.After PPVI, 13 patients were followed up for at least 12 months.The operation-related complications, improvement of valve and heart function and the durability and reintervention of the Venus-P self-expanding valve were analyzed.The right ventricular end-diastolic volume index (RVEDVi) before and after operation was compared by the paired t-test, and the New York Heart Association (NYHA) class was compared by the paired Wilcoxon signed rank sum test. Results:PPVI was successfully performed in all 13 patients without death.At 6 months post-PPVI, cardiac magnetic resonance imaging findings showed that RVEDVi was significantly reduced[(145.7±9.6) mL/m 2vs.(100.2±12.2) mL/m 2, P<0.05], and the NYHA class was significantly improved ( P<0.05). One patient presented moderate pulmonary valve regurgitation at 12 months postoperatively.No vegetation was found on echocardiography, and blood culture was negative in this case.Six patients did not have postoperative pulmonary valve regurgitation, and the remaining presented mild or less pulmonary regurgitation.One patient had sudden ventricular tachycardia on the 6 th day postoperatively, which was converted to sinus rhythm after synchronous electrocardiography.Only one case underwent appendectomy 7 months after operation due to acute appendicitis, and the remaining did not require valve-related reintervention after implantation.During the follow-up for (22.8±8.0) months, no patients had perivalve leakage, stent migration and rupture.Complications like embolization and coronary artery compression were not reported. Conclusions:PPVI using the Venus-P self-expanding valve is safe and effective in patients with severe pulmonary valve regurgitation after TOF surgery, showing an acceptable medium-term follow-up outcome.Studies with a large sample size and long follow-up period are still needed to validate our findings.