BACKGROUND:With the continuous advancement of medical technology,stem cell therapy has been used to treat a variety of diseases,including amyotrophic lateral sclerosis. OBJECTIVE:To review the research progress of stem cell therapy for amyotrophic lateral sclerosis,and prospect the development trend of this field. METHODS:PubMed,China National Knowledge Infrastructure(CNKI),and WanFang Data were searched for articles published from 1995 to 2024 using the key words"amyotrophic lateral sclerosis,mesenchymal stem cells,neural stem/progenitor cells,pluripotent stem cells."A total of more than 1 700 articles were retrieved,and 58 articles were finally included in this review. RESULTS AND CONCLUSION:Amyotrophic lateral sclerosis is a neurodegenerative disease that affects lower motor neurons in the brainstem and spinal cord and upper motor neurons in the motor cortex.The related research of stem cells in the treatment of amyotrophic lateral sclerosis has become a research hotspot.In this review,we summarize the application of different types of stem cells in amyotrophic lateral sclerosis research,including mesenchymal stem cells,neural stem progenitor cells,and induced pluripotent stem cells,and evaluate the key points of preclinical research such as stem cell source,cell volume,stem cell modification methods,and drug delivery routes,which lays the foundation for the future application of stem cell therapy.

Infectious diseases continue to pose a threat to global public health. Successive global shocks caused by emerging and re-emerging pathogens have continuously challenged existing surveillance systems, highlighting the urgent need to build efficient and precise pathogen surveillance networks. Pathogen genomic databases have been developed rapidly in recent two decades, significantly improving the molecular identification, evolutionary analysis, and transmission tracking of pathogens, and changing disease surveillance strategies and patterns. This paper summarizes the developmental history and current state of pathogen genomic databases, and discusses their applications in public health, including pathogen variation surveillance, emerging or suspected pathogen identification, and epidemiological tracing. Furthermore, this paper systematically analyzes the limitations and key challenges faced by current global health prevention and control system, and suggests the focus of the development of online pathogen databases to address existing shortcomings, ultimately improve global infectious disease surveillance and early warning

Based on advancements in modern medical research regarding the intricate connection between the endocrine and exocrine functions of the pancreas， as well as the relationship between pancreatic functions and traditional Chinese medicine （TCM） spleen system， this paper discussed the categorization of the pancreas. It is proposed that the pancreas is neither a true zang organ nor a fu organ， but possessed the attributes of an extraordinary fu-organ and can be classified under the spleen. The spleen governs transportation and transformation， ascent of the clear and dispersion of essence， which encompasses the endocrine and exocrine functions， and pancreatic enzymes and glucose-regulating hormones form the material basis for the spleen's function of dispersing essence. Diseases of the pancreas exhibit characteristics of both zang-organ deficiency and fu-organ excess， so treatment should simultaneously supplement zang-organ disease and regulate fu-organ disease when pancreas showing endocrine and exocrine co-morbidities， with focus on restoring the pancreas （spleen）'s dispersing essence function. Therapeutic strategies include supplementing spleen qi， nourishing spleen yin to strengthen spleen earth， unblocking spleen collaterals， raising spleen yang， and removing spleen turbidity to support the spleen's dispersing essence function， so as to replenish the essential qi of zang-fu organs， ensure their distribution throughout the body， and improve the endocrine and exocrine functions of the pancreas.

Objective To determine the effect of knee extension constraint training on bilateral knee biomechanics and bilateral symmetry in running after anterior cruciate ligament reconstruction(ACLR).Methods A total of 33 male patients with unilateral ACL injuries were randomly assigned to a BRACE group of 14 wearing a brace with limitation of knee extension,a PLACEBO group of 10 wear-ing a brace without limitation of knee extension,and a CONTROL group of 9,wearing no brace.All groups underwent unilateral hamstring-auto graft ACLR surgery,immediately followed by 12-week rou-tine rehabilitation.Between week 13 and 48,both the BRACE and PLACEBO groups wore braces for one hour on Mondays.Then,running biomechanical tests were performed at the ends of Week 12 and Week 48,and the bilateral knee extension/flexion angle,moment and inter-leg difference(ILD)were calculated.One-dimensional statistical parametric mapping(SPM1d)two-way ANOVA with repeated measures on one factor was used to identify differences in bilateral knee biomechanics and ILD among the three groups before and after the intervention.Results There was no significant interaction effect of group and time on bilateral knee flexion angle,knee extension moment,and ILD in running(P>0.05).Moreover,no significant effect of group was found on the bilateral knee biomechanics and ILD in running(P>0.05).Additionally,significant effects of time were observed on bilateral knee flexion angle and extension moment in running.However,bilateral knee flexion angle decreased during termi-nal stance(ACLR leg:89%～100%,P=0.036;non-ACLR leg:94%～100%,P=0.046),while the bi-lateral knee extension moment increased during mid-stance(ACLR leg:17%～59%,P<0.001;non-ACLR leg:38%～61%,P<0.001)between week 12 and 48.Conclusion In this study,no improvement was found in the abnormal knee biomechanics and symmetry during running in male patients after uni-lateral ACL reconstruction through long-term knee extension constraint training.Moreover,within one year after ACL reconstruction,the knee extension moment of the surgical limb increased gradually over time,with no changes in the knee flexion angle of the surgical limb and bilateral knee symme-try,suggesting that abnormal knee biomechanics and bilateral symmetry should be paid attention to in the post-surgery rehabilitation.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective To investigate the relationship between the expression of Osteoglycin(OGN)mRNA and Axis inhibitory protein 1(Axin1)mRNA and Epithelial-mesenchymal transition(EMT)and prognosis in cervical cancer(CC).Methods 142 patients with CC who were treated in Yulin Hospital,the First Affiliated Hospital of Xi'an Jiaotong University from April 2019 to April 2021 were collected.Real time fluorogenic quantitative PCR(RT-qPCR)was used to detect the expression of OGN mRNA,Axin1 mRNA and EMT markers Snail mRNA,N-cadherin(N-cad)mRNA,Vimentin(Vim)mRNA.The expression of OGN and Axin1 protein was detected by immunohistochemistry(IHC).Pearson correlation analysis was used to analyze the correlation between OGN mRNA,Axin1 mRNA and EMT indicators Snail mRNA,N-cad mRNA,Vim mRNA.The effect of OGN and Axin1 protein expression on the survival of CC was analyzed by Kaplan-Meier(K-M)survival curve and COX model.Results Compared with adjacent tissues,the expression of OGN mRNA in CC cancer tissues(0.84±0.22 vs 2.01±0.38)was lower,and the expression of Axin1 mRNA(2.41±0.42 vs 1.02±0.33)was higher,the differences were statistically significant(t=31.752,31.010,all P<0.001).Pearson correlation analysis,the expression of OGN mRNA was negatively correlated with that of Snail mRNA,N-cad mRNA and Vim mRNA(r=-0.765,-0.703,-0.697,all P<0.001).The expression of Axin1 mRNA was positively correlated with that of Snail mRNA,N-cad mRNA and Vim mRNA(r=0.771,0.798,0.690,all P<0.001).Compared with adjacent tissues,the positive rate of OGN protein in CC cancer tissues was lower[28.17%(40/142)vs 88.03%(125/142)],and the positive rate of Axin1 protein was higher[69.01%(98/142)vs 11.27%(16/142)],the differences were statistically significant(χ2=73.185,98.535,all P<0.001).Compared with patients with ⅠA-ⅠB1 and no lymph node metastasis,the positive rate of OGN protein in cancer tissues of patients with International Federation of Gynecology and Obstetrics(FIGO)stage Ⅰ B2-Ⅱ A and lymph node metastasis was lower,and the positive rate of Axin1 protein was higher,and the differences were statistically significant(χ2=4.315～13.252,all P<0.05).The 3-year overall survival rates of OGN positive group and negative group were 90.00%(36/40)and 70.59%(72/102),respectively,and the difference was statistically significant(Log-Rankχ2=7.140,P=0.008).The 3-year overall survival rates of Axin1 positive group and negative group were 69.39%(68/98)and 90.91%(40/44),respectively,and the difference was statistically significant(Log-Rankχ2=9.061,P=0.003).Axin1 positive,FIGO stage IB2～ⅡB,lymph node metastasis were risk factors for poor survival of CC,and OGN positive was a protective factor(Wald χ2=6.250～12.278,all P<0.05).Conclusion OGN is down-regulated and Axin1 is up-regulated in CC,which are related to EMT indicators and adverse survival outcomes of CC patients.

Objective To study the impact of tympanic membrane opening on respiratory-driven middle ear pressure in patients with patulous eustachian tube(PET),using a simplified in vitro model.Methods CT imaging data from a PET patient(with full-length eustachian tube opening observed during a Valsalva maneuver followed by breath-holding)were used to design a simplified eustachian tube model.Two simplified in vitro models of the eusta-chian tube were constructed using silicone-based 3D printing technology and connected to a pressure controller and pressure sensors.The pressure controller was activated to introduce negative-pressure airflow into the nasopharyn-geal model to simulate respiratory-induced middle ear pressure fluctuations.A hemostat was used to alternately open and close the external interface of the middle ear chamber,simulating conditions of an open and intact tympanic membrane,while middle ear pressure was continuously monitored using pressure sensors.Results In the first mod-el,with-800 mbar negative pressure applied at the nasopharynx,the middle ear pressure stabilized between-3.9 mbar and-4.3 mbar with tympanic membrane opening,and between-7.9 mbar and-8.2 mbar with intact tym-panic membrane.In the second model,under the same pressure setting,middle ear pressure stabilized between-2.7 mbar and-3.1 mbar with tympanic membrane opening,and between-5.0 mbar and-7.7 mbar with intact tympanic membrane.Conclusion This study,based on a simplified in vitro model,demonstrates that tympanic membrane opening can effectively reduce respiratory-driven pressure in the middle ear.This phenomenon may partly explain the clinical efficacy of tympanostomy tube insertion in certain PET patients.

Objective To investigate the relationship between the expression of Osteoglycin(OGN)mRNA and Axis inhibitory protein 1(Axin1)mRNA and Epithelial-mesenchymal transition(EMT)and prognosis in cervical cancer(CC).Methods 142 patients with CC who were treated in Yulin Hospital,the First Affiliated Hospital of Xi'an Jiaotong University from April 2019 to April 2021 were collected.Real time fluorogenic quantitative PCR(RT-qPCR)was used to detect the expression of OGN mRNA,Axin1 mRNA and EMT markers Snail mRNA,N-cadherin(N-cad)mRNA,Vimentin(Vim)mRNA.The expression of OGN and Axin1 protein was detected by immunohistochemistry(IHC).Pearson correlation analysis was used to analyze the correlation between OGN mRNA,Axin1 mRNA and EMT indicators Snail mRNA,N-cad mRNA,Vim mRNA.The effect of OGN and Axin1 protein expression on the survival of CC was analyzed by Kaplan-Meier(K-M)survival curve and COX model.Results Compared with adjacent tissues,the expression of OGN mRNA in CC cancer tissues(0.84±0.22 vs 2.01±0.38)was lower,and the expression of Axin1 mRNA(2.41±0.42 vs 1.02±0.33)was higher,the differences were statistically significant(t=31.752,31.010,all P<0.001).Pearson correlation analysis,the expression of OGN mRNA was negatively correlated with that of Snail mRNA,N-cad mRNA and Vim mRNA(r=-0.765,-0.703,-0.697,all P<0.001).The expression of Axin1 mRNA was positively correlated with that of Snail mRNA,N-cad mRNA and Vim mRNA(r=0.771,0.798,0.690,all P<0.001).Compared with adjacent tissues,the positive rate of OGN protein in CC cancer tissues was lower[28.17%(40/142)vs 88.03%(125/142)],and the positive rate of Axin1 protein was higher[69.01%(98/142)vs 11.27%(16/142)],the differences were statistically significant(χ2=73.185,98.535,all P<0.001).Compared with patients with ⅠA-ⅠB1 and no lymph node metastasis,the positive rate of OGN protein in cancer tissues of patients with International Federation of Gynecology and Obstetrics(FIGO)stage Ⅰ B2-Ⅱ A and lymph node metastasis was lower,and the positive rate of Axin1 protein was higher,and the differences were statistically significant(χ2=4.315～13.252,all P<0.05).The 3-year overall survival rates of OGN positive group and negative group were 90.00%(36/40)and 70.59%(72/102),respectively,and the difference was statistically significant(Log-Rankχ2=7.140,P=0.008).The 3-year overall survival rates of Axin1 positive group and negative group were 69.39%(68/98)and 90.91%(40/44),respectively,and the difference was statistically significant(Log-Rankχ2=9.061,P=0.003).Axin1 positive,FIGO stage IB2～ⅡB,lymph node metastasis were risk factors for poor survival of CC,and OGN positive was a protective factor(Wald χ2=6.250～12.278,all P<0.05).Conclusion OGN is down-regulated and Axin1 is up-regulated in CC,which are related to EMT indicators and adverse survival outcomes of CC patients.

Objective To study the impact of tympanic membrane opening on respiratory-driven middle ear pressure in patients with patulous eustachian tube(PET),using a simplified in vitro model.Methods CT imaging data from a PET patient(with full-length eustachian tube opening observed during a Valsalva maneuver followed by breath-holding)were used to design a simplified eustachian tube model.Two simplified in vitro models of the eusta-chian tube were constructed using silicone-based 3D printing technology and connected to a pressure controller and pressure sensors.The pressure controller was activated to introduce negative-pressure airflow into the nasopharyn-geal model to simulate respiratory-induced middle ear pressure fluctuations.A hemostat was used to alternately open and close the external interface of the middle ear chamber,simulating conditions of an open and intact tympanic membrane,while middle ear pressure was continuously monitored using pressure sensors.Results In the first mod-el,with-800 mbar negative pressure applied at the nasopharynx,the middle ear pressure stabilized between-3.9 mbar and-4.3 mbar with tympanic membrane opening,and between-7.9 mbar and-8.2 mbar with intact tym-panic membrane.In the second model,under the same pressure setting,middle ear pressure stabilized between-2.7 mbar and-3.1 mbar with tympanic membrane opening,and between-5.0 mbar and-7.7 mbar with intact tympanic membrane.Conclusion This study,based on a simplified in vitro model,demonstrates that tympanic membrane opening can effectively reduce respiratory-driven pressure in the middle ear.This phenomenon may partly explain the clinical efficacy of tympanostomy tube insertion in certain PET patients.