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.

Objective To explore the association between dynamic indexes of maternal progesterone in early pregnancy and the average level and growth rate of fetal head circumference(HC)in mid-and late pregnancy.Methods This study adopted a retrospective cohort design and included 255 singleton pregnant women in the maternal and infant cohort of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2024.The progesterone levels of their early venous blood were detected and divided into two groups of progesterone trajectories,namely,fluctuating type and increasing type,by morphology.The dynamic indicators of progesterone in early pregnancy were constructed:cumulative dynamic deviation index in the first trimester(CDDI-P1T),gestational age at progesterone peak(GA-PP),and maximal relative progesterone decline in the first trimester(MRD-P1T).The average head circumference level and linear growth rate of the fetuses in the middle and late pregnancy were calculated.Generalized linear regression(GLM)was used to analyze the linear association between progesterone dynamic indicators and head circumference development.The key gestational weeks of progesterone affecting fetal head development were explored by linear regression of gestational weeks.Ordinary least squares(OLS)regression and restricted cubic spline(RCS)plots were used to draw the nonlinear association between progesterone dynamic indicators and head circumference.Results Among the 255 pregnant women included,92.5％of the progesterone trajectories in early pregnancy were fluctuating,and 7.5％were increasing.The growth rates of the increasing progesterone trajectory group were higher in the second and third trimesters than in the fluctuating group,but the differences were not statistically significant(all P＞0.05).GLM analysis showed that for every 1 unit increase in CDDI-P1T,the head circumference in the middle and late pregnancy increased significantly by 1.574 cm and 1.193 cm(Z=3.714,2.885,P＜0.01).The delay of GA-PP was negatively correlated with the head circumference in the middle pregnancy(β=-0.190 cm,95％CI:-0.339--0.041,P=0.010)but positively correlated with the head circumference growth rate in the late pregnancy(β=0.022 cm/week,95％CI:0.003-0.041,P=0.025).A 10％decrease in the decline of CDDI-P1T increased the head circumference in the middle pregnancy by 0.200 cm(95％CI:0.016-0.384,P=0.033),and a 100％decrease in the decline increased the head circumference growth rate in the late pregnancy by 0.201 cm/week(95％CI:0.002-0.399,P=0.048).The analysis of the key time window showed that for every 20 nmol/L increase in progesterone during 9.5-13 weeks of pregnancy,the mid-term head circumference increased by 0.035-0.166 cm(Z=2.452-3.517,allP＜0.05),and the late-term head circumference increased by 0.767 cm during 9-13 weeks of pregnancy(Z=2.452-3.517,all P＜0.05).When progesterone increased during 9.5-10.5 weeks of pregnancy,the growth rate of mid-term head circumference increased by 0.013-0.023 cm/week(Z=2.074-2.243,all P＜0.01).When progesterone increased during 8.5-10.5 weeks of pregnancy,the growth rate of late-term head circumference increased by 0.010-0.026 cm/week(Z=2.061-3.137,all P＜0.05).Conclusion Progesterone dynamic index is a new sensitive tool for evaluating fetal head circumference development.There is a stage-specific window period for progesterone regulation.9.5-13 weeks of pregnancy is the critical period for progesterone to affect head circumference growth,and 9.5-10.5 weeks of pregnancy is the core window for regulating the growth rate of head circumference.Therefore,it is necessary to combine progesterone dynamic index and time window for individualized intervention to promote the transformation of prenatal care from pregnancy maintenance to eugenics intervention.

Objective To explore the association between dynamic indexes of maternal progesterone in early pregnancy and the average level and growth rate of fetal head circumference(HC)in mid-and late pregnancy.Methods This study adopted a retrospective cohort design and included 255 singleton pregnant women in the maternal and infant cohort of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2024.The progesterone levels of their early venous blood were detected and divided into two groups of progesterone trajectories,namely,fluctuating type and increasing type,by morphology.The dynamic indicators of progesterone in early pregnancy were constructed:cumulative dynamic deviation index in the first trimester(CDDI-P1T),gestational age at progesterone peak(GA-PP),and maximal relative progesterone decline in the first trimester(MRD-P1T).The average head circumference level and linear growth rate of the fetuses in the middle and late pregnancy were calculated.Generalized linear regression(GLM)was used to analyze the linear association between progesterone dynamic indicators and head circumference development.The key gestational weeks of progesterone affecting fetal head development were explored by linear regression of gestational weeks.Ordinary least squares(OLS)regression and restricted cubic spline(RCS)plots were used to draw the nonlinear association between progesterone dynamic indicators and head circumference.Results Among the 255 pregnant women included,92.5％of the progesterone trajectories in early pregnancy were fluctuating,and 7.5％were increasing.The growth rates of the increasing progesterone trajectory group were higher in the second and third trimesters than in the fluctuating group,but the differences were not statistically significant(all P＞0.05).GLM analysis showed that for every 1 unit increase in CDDI-P1T,the head circumference in the middle and late pregnancy increased significantly by 1.574 cm and 1.193 cm(Z=3.714,2.885,P＜0.01).The delay of GA-PP was negatively correlated with the head circumference in the middle pregnancy(β=-0.190 cm,95％CI:-0.339--0.041,P=0.010)but positively correlated with the head circumference growth rate in the late pregnancy(β=0.022 cm/week,95％CI:0.003-0.041,P=0.025).A 10％decrease in the decline of CDDI-P1T increased the head circumference in the middle pregnancy by 0.200 cm(95％CI:0.016-0.384,P=0.033),and a 100％decrease in the decline increased the head circumference growth rate in the late pregnancy by 0.201 cm/week(95％CI:0.002-0.399,P=0.048).The analysis of the key time window showed that for every 20 nmol/L increase in progesterone during 9.5-13 weeks of pregnancy,the mid-term head circumference increased by 0.035-0.166 cm(Z=2.452-3.517,allP＜0.05),and the late-term head circumference increased by 0.767 cm during 9-13 weeks of pregnancy(Z=2.452-3.517,all P＜0.05).When progesterone increased during 9.5-10.5 weeks of pregnancy,the growth rate of mid-term head circumference increased by 0.013-0.023 cm/week(Z=2.074-2.243,all P＜0.01).When progesterone increased during 8.5-10.5 weeks of pregnancy,the growth rate of late-term head circumference increased by 0.010-0.026 cm/week(Z=2.061-3.137,all P＜0.05).Conclusion Progesterone dynamic index is a new sensitive tool for evaluating fetal head circumference development.There is a stage-specific window period for progesterone regulation.9.5-13 weeks of pregnancy is the critical period for progesterone to affect head circumference growth,and 9.5-10.5 weeks of pregnancy is the core window for regulating the growth rate of head circumference.Therefore,it is necessary to combine progesterone dynamic index and time window for individualized intervention to promote the transformation of prenatal care from pregnancy maintenance to eugenics intervention.

OBJECTIVE To explore the functional substance basis of Jinhong Tablet in the treatment of chronic superficial gastri-tis(CSG).METHODS Three different models were constructed to investigate the anti-inflammatory and antioxidant effects,func-tional material basis of Jinhong Tablet:inflammatory model in human gastric epithelial cells(GES-1)induced by lipopolysaccharide(LPS),LPS-induced inflammatory model in mouse gastric organoids,and ethanol-induced oxidative damage model in GES-1 cells.MTS assay was performed to detect cell proliferation activity;qPCR was applied to measure the relative mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-8(IL-8)in cells and gastric organoids;and the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and reactive oxygen species(ROS)in cells were detected.RESULTS Jinhong Tablet and 10 functional components significantly reduced the relative expression of inflammation-relat-ed genes TNF-α,IL-1β,IL-6,and IL-8 in LPS-induced GES-1 cells and gastric organoids,suggesting that these 10 components are the functional substance basis for the anti-inflammatory effects of Jin Hong Tablet.Jin Hong Tablet and 11 functional components markedly decreased the levels of MDA and ROS and increased the activity of SOD,indicating that these 11 components were the func-tional substance basis of the antioxidant effects of Jinhong Tablet.CONCLUSION Through in vitro cell and gastric organoid experi-ments,it has been preliminarily determined that allocryptopine,corydaline,dehydrocorydaline,palmatine hydrochloride,chlorogenic acid,costunolide,rutin,quercitrin,dehydrocostus lactone,tetrahydrocoptisine,isochlorogenic acid B,toosendanin,protopine,and quercetin are the functional material basis of Jinhong Tablet in treating CSG,accumulating scientific evidence for the enhancement of the quality standards of Jinhong Tablet.

Botulinum toxin poisoning can lead to severe health crises, and multidisciplinary collaboration is crucial for rapid diagnosis and emergency treatment. This article reported a case of a 21-year-old female patient who developed symptoms of botulinum toxin poisoning 4 days after receiving botulinum toxin type A through an unofficial route. Significant symptomatic improvement was observed 9 days after the onset of poisoning following botulinum antitoxin treatment. Through a case report and a review of neurophysiological literature, the role of neurophysiological examinations in aiding diagnosis was analyzed, providing a scientific basis for clinical treatment..

Objective:Analyze the clinicopatholocical and imaging characteristics of hepatic epithelioid hemangioendothelioma (HEHE) and the related factors of survival prognosis.Methods:Clinical data of 32 patients diagnosed with HEHE at the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023 retrospectively analyzed, including 11 males and 21 females, aged (46.8±3.6) years. The clinical manifestations, pathological findings, CT and MRI features of the patients were analyzed and the living conditions of the patients were followed up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival rate comparison.Results:Among the 32 patients, 17 (53.1%) had no obvious symptoms, 10 (31.3%) had abdominal pain, 6 (18.8%) had abdominal distension, and 4 (12.5%) had lost weight. Under the microscope, HEHE was composed of mucous matrix and epithelioid endothelial cells, with dense surrounding cells and relatively sparse center. Small blood vessels can be seen invading the junction with normal liver tissue. The positive rates of endothelial marker CD34 in immunohistochemically staining was 100%(32/32), the positive rates of CD31 were 100% (32/32). The positive rates of erythroblast transformation specific related gene were 100% (28/28), and the positive rates of Friend leukemia virus integration protein 1 (22/22) were 100%. CT and MRI scan showed that the lesion were mainly multiple nodules and in diffuse formality. In arterial phase, the lesion showed slight homogeneous or ring-like enhancement, while in portal phase, the lesion showed progressive enhancement. Some lesions may exhibit more specific "lollipop sign" ( n=9) and "target ring sign" ( n=15). The median overall survival time of the 32 patients was 47 months, and the cumulative 1-, 3-, and 5-year survival were 100%, 95.0% and 72.7%, respectively. The cumulative survival rate of patients with "target ring sign" ( n=15), extrahepatic organ involvement or metastasis ( n=8) and Ki-67 positive rate >5% ( n=10) were lower than those without the above characteristics (all P<0.05). Conclusion:The clinical manifestations of HEHE were not typical, and the tumor was rich in mucus matrix and epithelioid endothelial cells, expressing endothelial markers. CT and MRI scan mainly showed multiple nodules or diffused lesion, and the "lollipop sign" and "target ring sign" were helpful for diagnosis. HEHE patients with Ki-67 positivity rate >5%, "target ring sign", and extrahepatic organs involvement or metastasis had a poor prognosis.

OBJECTIVE To explore the functional substance basis of Jinhong Tablet in the treatment of chronic superficial gastri-tis(CSG).METHODS Three different models were constructed to investigate the anti-inflammatory and antioxidant effects,func-tional material basis of Jinhong Tablet:inflammatory model in human gastric epithelial cells(GES-1)induced by lipopolysaccharide(LPS),LPS-induced inflammatory model in mouse gastric organoids,and ethanol-induced oxidative damage model in GES-1 cells.MTS assay was performed to detect cell proliferation activity;qPCR was applied to measure the relative mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-8(IL-8)in cells and gastric organoids;and the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and reactive oxygen species(ROS)in cells were detected.RESULTS Jinhong Tablet and 10 functional components significantly reduced the relative expression of inflammation-relat-ed genes TNF-α,IL-1β,IL-6,and IL-8 in LPS-induced GES-1 cells and gastric organoids,suggesting that these 10 components are the functional substance basis for the anti-inflammatory effects of Jin Hong Tablet.Jin Hong Tablet and 11 functional components markedly decreased the levels of MDA and ROS and increased the activity of SOD,indicating that these 11 components were the func-tional substance basis of the antioxidant effects of Jinhong Tablet.CONCLUSION Through in vitro cell and gastric organoid experi-ments,it has been preliminarily determined that allocryptopine,corydaline,dehydrocorydaline,palmatine hydrochloride,chlorogenic acid,costunolide,rutin,quercitrin,dehydrocostus lactone,tetrahydrocoptisine,isochlorogenic acid B,toosendanin,protopine,and quercetin are the functional material basis of Jinhong Tablet in treating CSG,accumulating scientific evidence for the enhancement of the quality standards of Jinhong Tablet.

Botulinum toxin poisoning can lead to severe health crises, and multidisciplinary collaboration is crucial for rapid diagnosis and emergency treatment. This article reported a case of a 21-year-old female patient who developed symptoms of botulinum toxin poisoning 4 days after receiving botulinum toxin type A through an unofficial route. Significant symptomatic improvement was observed 9 days after the onset of poisoning following botulinum antitoxin treatment. Through a case report and a review of neurophysiological literature, the role of neurophysiological examinations in aiding diagnosis was analyzed, providing a scientific basis for clinical treatment..

Objective:Analyze the clinicopatholocical and imaging characteristics of hepatic epithelioid hemangioendothelioma (HEHE) and the related factors of survival prognosis.Methods:Clinical data of 32 patients diagnosed with HEHE at the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023 retrospectively analyzed, including 11 males and 21 females, aged (46.8±3.6) years. The clinical manifestations, pathological findings, CT and MRI features of the patients were analyzed and the living conditions of the patients were followed up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival rate comparison.Results:Among the 32 patients, 17 (53.1%) had no obvious symptoms, 10 (31.3%) had abdominal pain, 6 (18.8%) had abdominal distension, and 4 (12.5%) had lost weight. Under the microscope, HEHE was composed of mucous matrix and epithelioid endothelial cells, with dense surrounding cells and relatively sparse center. Small blood vessels can be seen invading the junction with normal liver tissue. The positive rates of endothelial marker CD34 in immunohistochemically staining was 100%(32/32), the positive rates of CD31 were 100% (32/32). The positive rates of erythroblast transformation specific related gene were 100% (28/28), and the positive rates of Friend leukemia virus integration protein 1 (22/22) were 100%. CT and MRI scan showed that the lesion were mainly multiple nodules and in diffuse formality. In arterial phase, the lesion showed slight homogeneous or ring-like enhancement, while in portal phase, the lesion showed progressive enhancement. Some lesions may exhibit more specific "lollipop sign" ( n=9) and "target ring sign" ( n=15). The median overall survival time of the 32 patients was 47 months, and the cumulative 1-, 3-, and 5-year survival were 100%, 95.0% and 72.7%, respectively. The cumulative survival rate of patients with "target ring sign" ( n=15), extrahepatic organ involvement or metastasis ( n=8) and Ki-67 positive rate >5% ( n=10) were lower than those without the above characteristics (all P<0.05). Conclusion:The clinical manifestations of HEHE were not typical, and the tumor was rich in mucus matrix and epithelioid endothelial cells, expressing endothelial markers. CT and MRI scan mainly showed multiple nodules or diffused lesion, and the "lollipop sign" and "target ring sign" were helpful for diagnosis. HEHE patients with Ki-67 positivity rate >5%, "target ring sign", and extrahepatic organs involvement or metastasis had a poor prognosis.

Objective:To investigate the predictive value of thyroid peroxidase antibody(TPOAb), thyroglobulin antibody(TgAb), and thyrotropin receptor antibody(TRAb) status prior to the first 131I treatment in the development of hypothyroidism in patients with Graves′ disease after 131I administration. Methods:The cohort of 89 males and 351 females, with a median age of 34 years (IQR 28-44) who underwent initial 131I therapy at Peking Union Medical College Hospital from December 2019 to December 2021 was established. Participants were classified into TPOAb-positive, TgAb-positive, TRAb-positive, and their respective negative groups based on pre-treatment serum levels of thyroid autoantibody. Sex, age, medical history, thyroid hormone level, thyroid autoantibodies, iodine uptake rate, thyroid estimation and 131I treatment dose were recorded. The 131I treatment dose was determined using the calculated dose method. Patients were followed up for one-year post-treatment to evaluate efficacy. Mann- Whitney U test and χ 2 test were used to compare and analyze the data between groups, and logistic regression was used to analyze the influencing factors of permanent hypothyroidism after treatment. Results:(1) In the TPOAb-positive group, transient hypothyroidism and permanent hypothyroidism occurred in 8.1%(26/321) and 44.9%(144/321), both of which were significantly higher than those in the TPOAb-negative group at 2.5%(3/119) and 31.9%(38/119); In the TRAb-negative group, permanent hypothyroidism occurred in 56.8%(25/44), which was significantly higher than that in the TRAb-positive group 39.5%(152/385). (2) After the first 131I treatment, males ( OR=0.518, 95% CI 0.314-0.855, P=0.010), TPOAb-positive ( OR=1.002, 95% CI 1.001-1.003, P=0.001), and TRAb-negative( OR=0.973, 95% CI 0.957-0.990, P=0.002) were independent influence factor, of permanent hypothyroidism. Conclusion:In the calculated dose method for treating GD, male, TPOAb-positivity, and TRAb-negativity prior to initial 131I treatment are associated with a higher likelihood of developing permanent hypothyroidism post-treatment.