BACKGROUND:The exact pathogenesis of temporomandibular joint osteoarthritis is currently unclear.Traditional clinical treatment strategies for temporomandibular joint osteoarthritis are symptomatic treatments such as pain relief and reduction of inflammation,which can stop the progression of the disease to a certain degree but cannot reverse the destruction of the cartilage.Cartilage degeneration,as one of the most prominent pathologic features in the development of temporomandibular joint osteoarthritis,has been the subject of an increasing number of studies that focus on its pathogenesis.Consequently,we hope to provide an ideal radical solution for the regeneration of the temporomandibular joint.OBJECTIVE:To review the progress of research on cartilage degeneration in temporomandibular joint osteoarthritis.METHODS:The search terms were"temporomandibular joint osteoarthritis,degradation of cartilage matrix,synovitis,oxidative stress,chondrocyte hypertrophy,chondrocyte apoptosis,ferroptosis,autophagy,angiogenesis,extracellular vesicles"in Chinese and English.Literature search was conducted in PubMed database and CNKI,and the time limit for the search was from January 2004 to October 2024.Screening was performed by analyzing and reading the literature,and according to the inclusion and exclusion criteria,81 papers were finally included for review.RESULTS AND CONCLUSION:(1)Increased secretion of cartilage matrix degrading enzymes causes degradation of the cartilage matrix,leading to cartilage degeneration.(2)Synovitis promotes cartilage degeneration through macrophage M1-type polarization and production of inflammatory mediators.(3)Oxidative stress promotes cartilage degeneration by exacerbating the inflammatory response through overproduction of reactive oxygen species.(4)Chondrocyte phenotypic changes and death lead to the decrease of cartilage matrix synthesis,resulting in cartilage degeneration.(5)Blood vessels of subchondral bone penetrate the calcified cartilage layer to reach the superficial cartilage layer,which destroys the cartilage structure and leads to cartilage degeneration.(6)Bioactive substances carried by serum-derived extracellular vesicles in inflammatory states also promote cartilage degeneration in temporomandibular joint osteoarthritis.

BACKGROUND:The exact pathogenesis of temporomandibular joint osteoarthritis is currently unclear.Traditional clinical treatment strategies for temporomandibular joint osteoarthritis are symptomatic treatments such as pain relief and reduction of inflammation,which can stop the progression of the disease to a certain degree but cannot reverse the destruction of the cartilage.Cartilage degeneration,as one of the most prominent pathologic features in the development of temporomandibular joint osteoarthritis,has been the subject of an increasing number of studies that focus on its pathogenesis.Consequently,we hope to provide an ideal radical solution for the regeneration of the temporomandibular joint.OBJECTIVE:To review the progress of research on cartilage degeneration in temporomandibular joint osteoarthritis.METHODS:The search terms were"temporomandibular joint osteoarthritis,degradation of cartilage matrix,synovitis,oxidative stress,chondrocyte hypertrophy,chondrocyte apoptosis,ferroptosis,autophagy,angiogenesis,extracellular vesicles"in Chinese and English.Literature search was conducted in PubMed database and CNKI,and the time limit for the search was from January 2004 to October 2024.Screening was performed by analyzing and reading the literature,and according to the inclusion and exclusion criteria,81 papers were finally included for review.RESULTS AND CONCLUSION:(1)Increased secretion of cartilage matrix degrading enzymes causes degradation of the cartilage matrix,leading to cartilage degeneration.(2)Synovitis promotes cartilage degeneration through macrophage M1-type polarization and production of inflammatory mediators.(3)Oxidative stress promotes cartilage degeneration by exacerbating the inflammatory response through overproduction of reactive oxygen species.(4)Chondrocyte phenotypic changes and death lead to the decrease of cartilage matrix synthesis,resulting in cartilage degeneration.(5)Blood vessels of subchondral bone penetrate the calcified cartilage layer to reach the superficial cartilage layer,which destroys the cartilage structure and leads to cartilage degeneration.(6)Bioactive substances carried by serum-derived extracellular vesicles in inflammatory states also promote cartilage degeneration in temporomandibular joint osteoarthritis.

Objective To determine the predictive power of negative fluid balance in the risk of death in septic shock patients after fluid resuscitation therapy.Methods The medical records of patients with septic shock admitted to the Intensive Care Department of Tianjin Medical University Cancer Hospital from March 2022 to December 2024 were retrospectively collected,and the final outcome was defined as death within 28 days during hospitalization.The study objects were randomly divided into the training set and the validation set,and then the model was built by Logistic regression method,and the nomogram and receiver operating characteristic curve(ROC curve)were drawn.Hosmer-Lemeshow test was used to evaluate the calibration degree of the prediction model,and the calibration curve was drawn to evaluate the differentiation degree of the prediction model.Decision curve analysis(DCA)was used to test the efficiency of the prediction model.Results A total of 286 patients with septic shock were included in the study,including 200 in the training set and 86 in the verification set,which were comparable.Multivariate Logistic regression analysis showed that negative fluid balance,APACHE II score and SOFA score were independent risk factors for poor survival and prognosis of ICU septic shock patients(all P<0.05).Based on the results of multivariate Logistic regression analysis,a nomogram was constructed to predict the survival and prognosis of patients with septic shock in ICU.In the training set and validation set,the area under the curve(AUC)of the ROC curve prediction model was 0.83(95%CI:0.73～0.93)and 0.83(95%CI:0.66～1.00),respectively.Hosmer-Lemeshow calibration curve has a good fit(training set P=0.169;The verification set P=1.000)is not significant.DCA showed that when the threshold probability of patients was 0.05～0.70,it was more beneficial to use the nomogram prediction model to predict the risk of death in septic shock patients.Conclusion Negative fluid balance after fluid resuscitation is associated with survival and prognosis of patients with septic shock.The predictive model of mortality risk of patients with septic shock was established by combining APACHEⅡ score and SOFA score,which has good predictive ability and clinical practicability.

With the widespread useof immune checkpoint inhibitors(ICIs)in the treatment of various solid tumors,immune-related adverse events have attracted increasing clinical attention.Although ICI-associated myocarditis is rare,it typically has an insidious onset,progresses rapidly,and carries a high mortality rate,making it one of the most severe complications of ICI therapy.Early recognition and management remain challenging due to the absence of standardized diagnostic and therapeutic guidelines.ICI-associated myocarditis is characterized by the following features,with symptom onset commonly occurring within weeks of initiating ICI therapy.Its clinical manifestations are often non-specific and can be misdiagnosed as coronary artery disease or viral myocarditis.Prompt administration of high-dose corticosteroids combined with immunosuppressants,cardiac rhythm and functional support,is crucial for effective management.Although numerous stud-ies highlight the importance of early detection and multidisciplinary collaboration,there is still no consensus on standardized treatment pro-tocols.This report describes a case of acute ICI-associated myocarditis with ovarian cancer who developed symptoms after receiving com-bined apalutamide and toripalimab therapy.The patient responded well to corticosteroid pulse therapy,second-line immunosuppressants,and intensive care support.Due to recurrent ventricular arrhythmias,an implantable cardioverter defibrillator was placed,and cardiac func-tion remained stable during follow-up.Through this case and a review of the relevant literature,we discuss the clinical features,compre-hensive treatment strategies,and long-term management approaches for ICI-associated myocarditis,aiming to raise clinical awareness,pro-mote standardized multidisciplinary team collaboration,and ultimately improve patient outcomes.

Acute pancreatitis(AP)is a frequently encountered acute abdominal syndrome in clinical settings,and the integrated model of traditional Chinese and Western medicine(TCM-WM)has demonstrated notable advantages in the diagnosis and treatment of AP.To systematize and standardize clinical practices related to develop clinical pathway for integrated TCM-WM diagnosis and treatment of AP,which enhances the efficiency and quality of patient care.This pathway focuses on AP,a common acute and life-threatening disease within the digestive system,and outlines that the central pathological mechanism involves pancreatic injury and localized inflammation resulting from the abnormal activation of pancreatic enzymes.It has the characteristics of rapid onset,multiple causes,and complex manifestations.Severe cases can be life-threatening.At present,conventional treatments encompass a diverse range of modalities.Moreover,traditional Chinese medicine(TCM)holds distinct advantages in alleviating relevant symptoms,and TCM-WM is gaining increasing prevalence.To enhance the standardization and consistency of diagnostic and therapeutic practices,this clinical pathway clearly delineates the target patient population,which includes individuals diagnosed with abdominal pain disorder according to TCM and with AP in accordance with WM criteria,as well as the corresponding inclusion standards.The diagnostic framework integrates both TCM and WM guidelines,and further incorporates disease staging,severity grading,and syndrome differentiation to support a comprehensive and integrated diagnostic strategy.The treatment integrates approaches from both TCM and WM.Within the WM framework,interventions consist of basic supportive care,infection control,nutritional support,and the management of complications.In the context of TCM,the protocol includes syndrome differentiation and corresponding therapeutic strategies(Distinct syndrome patterns are identified and managed during the acute and convalescent phases),such as acupuncture and retention enema.This clinical pathway addresses multiple key components,including preventive strategies,post-treatment follow-up,criteria for evaluating therapeutic efficacy,admission and discharge,admission examination protocols,discharge criteria,and the rationale for deviations or withdrawal from the pathway.It is designed to provide a systematic and standardized reference framework for relevant clinical practices.

The application of genetic testing technologies in assisted reproduction, such as preimplantation genetic testing (PGT) and carrier screening for monogenic diseases, has provided infertile couples with more reproductive options and played a crucial role in the prevention of genetic disorders, significantly improving reproductive health. However, the widespread use of these technologies has also raised various ethical challenges, including the uncertainty of mosaic embryo transfer and its implications for reproductive rights, the cost-effectiveness debate surrounding PGT for structural rearrangement for chromosomal inversion carriers, the predictive accuracy and ethical boundaries of polygenic embryo screening, and the ethical concerns related to extensive carrier screening, such as information overload, restricted informed choice, disputes over screening scope, and disparities in healthcare access. The reproductive medicine ethics committee plays a central role in addressing these challenges by overseeing ethical reviews of technological applications, ensuring patients' informed consent, balancing technological innovation with ethical responsibility, and promoting social equity. This article explores the ethical challenges brought by the application of technologies such as PGT and carrier screening in assisted reproduction, and proposes corresponding suggestions based on ethical principles framework, in order to promote the standardized application of genetic testing technology in reproductive medicine.

The application of genetic testing technologies in assisted reproduction, such as preimplantation genetic testing (PGT) and carrier screening for monogenic diseases, has provided infertile couples with more reproductive options and played a crucial role in the prevention of genetic disorders, significantly improving reproductive health. However, the widespread use of these technologies has also raised various ethical challenges, including the uncertainty of mosaic embryo transfer and its implications for reproductive rights, the cost-effectiveness debate surrounding PGT for structural rearrangement for chromosomal inversion carriers, the predictive accuracy and ethical boundaries of polygenic embryo screening, and the ethical concerns related to extensive carrier screening, such as information overload, restricted informed choice, disputes over screening scope, and disparities in healthcare access. The reproductive medicine ethics committee plays a central role in addressing these challenges by overseeing ethical reviews of technological applications, ensuring patients' informed consent, balancing technological innovation with ethical responsibility, and promoting social equity. This article explores the ethical challenges brought by the application of technologies such as PGT and carrier screening in assisted reproduction, and proposes corresponding suggestions based on ethical principles framework, in order to promote the standardized application of genetic testing technology in reproductive medicine.

Objective:To construct a calcium alginate (ALG-Ca 2+) composite hydrogel loaded with chlorella protein (Cp) (ALG-Ca 2+@Cp) and investigate its combined effect with microwave hyperthermia on the proliferation, apoptosis, and immune activation of mouse pancreatic cancer cells. Methods:ALG-Ca 2+@Cp was prepared using a physical cross-linking method and its physiochemical properties was characterized via scanning electron microscopy, rheological analysis, Ca 2+ release experiments, and microwave thermal conversion tests. The BCA protein quantification assay was used to evaluate the adsorption capacity of ALG-Ca 2+@Cp for pancreatic cancer cell antigens. The effects of ALG-Ca 2+@Cp extract combined with microwave intervention on pancreatic cancer cell proliferation, apoptosis protein expression, and cell viability were assessed using CCK-8 assays, ELISA, and Calcein-AM/PI double fluorescence staining. Flow cytometry was performed to determine the maturation-promoting ability of ALG-Ca 2+@Cp on immature mouse bone marrow-derived dendritic cells (BMDCs). Results:ALG-Ca 2+@Cp exhibited a three-dimensional network structure with a storage modulus (G') greater than the loss modulus (G''), demonstrating typical hydrogel properties. The hydrogel loaded with 0.5 mol/ml Ca 2+ reached 48°C after 5 minutes of microwave irradiation at 5.0 W/cm 2, and Ca 2+ release plateaued within 5 minutes. ALG-Ca 2+@Cp effectively adsorbed pancreatic cancer cell antigens. Combined with microwave treatment, it significantly reduced pancreatic cancer cell proliferation ( A450 value 0.39±0.07 vs 2.78±0.15) and increased apoptosis markers calreticulin (CRT) and high mobility group box-1 protein (HMGB1) [(557.09±37.84) pg/ml vs (135.14±11.84) pg/ml, (4.77±0.18) ng/ml vs (1.6±0.16) ng/ml], leading to decreased cell viability; and all the differences were statistically significant (all P value <0.05). ALG-Ca 2+@Cp synergistically promoted the maturation of immature BMDCs in the presence of pancreatic cancer antigens, with a CD 80+ positivity rate of (75.67±6.53)%. Conclusions:ALG-Ca 2+@Cp is successfully constructed. Its combination with microwave hyperthermia can significantly enhance the cytotoxicity and immune activation against mouse pancreatic cancer cells by targeting intracellular antigens and inducing immunogenic cell death.

Objective To determine the predictive power of negative fluid balance in the risk of death in septic shock patients after fluid resuscitation therapy.Methods The medical records of patients with septic shock admitted to the Intensive Care Department of Tianjin Medical University Cancer Hospital from March 2022 to December 2024 were retrospectively collected,and the final outcome was defined as death within 28 days during hospitalization.The study objects were randomly divided into the training set and the validation set,and then the model was built by Logistic regression method,and the nomogram and receiver operating characteristic curve(ROC curve)were drawn.Hosmer-Lemeshow test was used to evaluate the calibration degree of the prediction model,and the calibration curve was drawn to evaluate the differentiation degree of the prediction model.Decision curve analysis(DCA)was used to test the efficiency of the prediction model.Results A total of 286 patients with septic shock were included in the study,including 200 in the training set and 86 in the verification set,which were comparable.Multivariate Logistic regression analysis showed that negative fluid balance,APACHE II score and SOFA score were independent risk factors for poor survival and prognosis of ICU septic shock patients(all P<0.05).Based on the results of multivariate Logistic regression analysis,a nomogram was constructed to predict the survival and prognosis of patients with septic shock in ICU.In the training set and validation set,the area under the curve(AUC)of the ROC curve prediction model was 0.83(95%CI:0.73～0.93)and 0.83(95%CI:0.66～1.00),respectively.Hosmer-Lemeshow calibration curve has a good fit(training set P=0.169;The verification set P=1.000)is not significant.DCA showed that when the threshold probability of patients was 0.05～0.70,it was more beneficial to use the nomogram prediction model to predict the risk of death in septic shock patients.Conclusion Negative fluid balance after fluid resuscitation is associated with survival and prognosis of patients with septic shock.The predictive model of mortality risk of patients with septic shock was established by combining APACHEⅡ score and SOFA score,which has good predictive ability and clinical practicability.

Objective:To construct a calcium alginate (ALG-Ca 2+) composite hydrogel loaded with chlorella protein (Cp) (ALG-Ca 2+@Cp) and investigate its combined effect with microwave hyperthermia on the proliferation, apoptosis, and immune activation of mouse pancreatic cancer cells. Methods:ALG-Ca 2+@Cp was prepared using a physical cross-linking method and its physiochemical properties was characterized via scanning electron microscopy, rheological analysis, Ca 2+ release experiments, and microwave thermal conversion tests. The BCA protein quantification assay was used to evaluate the adsorption capacity of ALG-Ca 2+@Cp for pancreatic cancer cell antigens. The effects of ALG-Ca 2+@Cp extract combined with microwave intervention on pancreatic cancer cell proliferation, apoptosis protein expression, and cell viability were assessed using CCK-8 assays, ELISA, and Calcein-AM/PI double fluorescence staining. Flow cytometry was performed to determine the maturation-promoting ability of ALG-Ca 2+@Cp on immature mouse bone marrow-derived dendritic cells (BMDCs). Results:ALG-Ca 2+@Cp exhibited a three-dimensional network structure with a storage modulus (G') greater than the loss modulus (G''), demonstrating typical hydrogel properties. The hydrogel loaded with 0.5 mol/ml Ca 2+ reached 48°C after 5 minutes of microwave irradiation at 5.0 W/cm 2, and Ca 2+ release plateaued within 5 minutes. ALG-Ca 2+@Cp effectively adsorbed pancreatic cancer cell antigens. Combined with microwave treatment, it significantly reduced pancreatic cancer cell proliferation ( A450 value 0.39±0.07 vs 2.78±0.15) and increased apoptosis markers calreticulin (CRT) and high mobility group box-1 protein (HMGB1) [(557.09±37.84) pg/ml vs (135.14±11.84) pg/ml, (4.77±0.18) ng/ml vs (1.6±0.16) ng/ml], leading to decreased cell viability; and all the differences were statistically significant (all P value <0.05). ALG-Ca 2+@Cp synergistically promoted the maturation of immature BMDCs in the presence of pancreatic cancer antigens, with a CD 80+ positivity rate of (75.67±6.53)%. Conclusions:ALG-Ca 2+@Cp is successfully constructed. Its combination with microwave hyperthermia can significantly enhance the cytotoxicity and immune activation against mouse pancreatic cancer cells by targeting intracellular antigens and inducing immunogenic cell death.