Objective To explore risk factors of sodium-dependent glucose transporters 2 （SGLT2） inhibitor-associated euglycemic diabetic ketoacidosis （euDKA） and to construct a risk prediction model. Methods A retrospective analysis was performed on the clinical data of type 2 diabetes patients treated with SGLT2 inhibitors in Dongnan Hospital of Xiamen University from January 2020 to December 2023, including age, gender and course of diabetes. The risk factors of SGLT2 inhibitor-associated euDKA were analyzed by univariate analysis and multivariate Logistic regression, and a prediction model was established. According to the receiver's operating characteristic （ROC） curve, the area under the curve （AUC） and the optimal critical value of the prediction model were determined. The prediction model was subjected to both internal and external validation. Results A total of 119 patients with type 2 diabetes treated with SGLT2 inhibitors were included in this study. Among them, there were 98 cases without euDKA （non-euDKA group）and 21 cases with euDKA （euDKA group）. Multivariate Logistic regression analysis showed the DKA history (OR=114.153), appetite or diet decreased three days before admission (OR=21.774), elevated neutrophil count (OR=2.056) and pre-hospital adjustment of hypoglycemic agents (OR=45.745) were independent factors to increase risks of euDKA associated with SGLT2 inhibitors （P<0.05）. Surgical history before admission was an independent factor to reduce this risk （OR=0.007, P<0.05）. By establishing the calculation formula of the prediction model = neutrophil count+6.571 （DKA history）−6.874 （surgical history before admission）+4.273 （appetite or diet decreased three days before admission）+5.302 （pre-hospital adjustment of hypoglycemic drugs）, the ROC curve was drawn. The AUC of the ROC of the prediction model was 0.982 （95%CI: 0.961-1.000, P<0.001）, with accuracy of 94.96%, sensitivity of 0.905, specificity of 0.959 and a critical value of 7.405. The AUC of ROC curve after the model’s ten-fold cross validation was 0.930. And the accuracy of the external validation of the prediction model was 85.29%. Conclusion The DKA history, appetite or diet decreased three days before admission, elevated neutrophil count and pre-hospital adjustment of hypoglycemic agents increased the risk of SGLT2 inhibitor-associated euDKA, while the surgical history before admission reduced this risk. The risk prediction model constructed on this basis could better predict the risk of SGLT2 inhibitor-associated euDKA.

Objective:To investigate the relationship between the level of angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) in the uterine fluid and the thickness of endometrium in infertile women with chronic endometritis.Methods:A case-control study was conducted to select 122 patients who underwent hysteroscopy and endometrial tissue biopsy at Assisted Reproduction Center, Taiyuan Central Hospital due to infertility from March 2023 to January 2024 as the study subjects. According to the results of hysteroscopy and endometrial tissue biopsy, the patients were divided into 52 cases in the infertility group with normal endometrium (NE infertility group) and the chronic endometritis combined with infertility group (CE infertility group) with 70 cases. Enzyme-linked immunosorbent assay was used to detect the level of AT1-AA in uterine fluid of the two groups. General clinical data, AT1-AA absorbance value of uterine fluid and uterine related indexes of the two groups were analyzed, and the correlations between AT1-AA level and the variation of indexes were analyzed.Results:Gravidity (median: 1 vs 1; Z=7.029, P=0.030) and parity (median: 0 vs 0; Z=12.258, P=0.002) in CE infertility group were higher than those in NE infertility group. There was AT1-AA in the uterine fluid, and the level of AT1-AA in CE infertility group was significantly higher than that in NE infertility group (median: 2.07 vs 1.44; Z=3.099, P=0.029). The endometrial thickness of CE infertility group was lower than that of NE infertility group (median: 6.0 vs 7.0 mm; Z=-2.179, P=0.029), and there were no statistical differences in other indexes between the two groups (all P>0.05). Further correlation analysis showed that there were no correlation between the level of AT1-AA in uterine fluid and parity, endometrial thickness, gravidity in NE infertility group (all P>0.05). However, the level of AT1-AA in uterine fluid of CE infertility group was positively correlated with parity (Spearman′s r=0.339, P=0.004), and negatively correlated with endometrial thickness (Spearman′s r=-0.499, P<0.001), but not correlated with gravidity ( P>0.05). Conclusions:AT1-AA is present in the uterine fluid of infertile women. The elevated level of AT1-AA in uterine fluid of infertile women with CE is related to the thinning of the endometrium.

Objective:To investigate the mechanism of recombinant human mesencephalic astrocyte-derived neurotrophic factor (rhMANF) in spinal cord injury (SCI) repair promoted by A2 reactive astrocyte polarization.Methods:One hundred and twenty female SPF SD rats were randomly divided into sham-operated group, SCI group, SCI+control group and SCI+rhMANF group ( n=30 in each group). SCI models were prepared by heavy drop method in the later 3 groups, and 10 μL sterile saline or 10 μL sterile saline+5 μg rhMANF were injected intrathecally in the later 2 groups 30 min after modeling. Basso-Beattie-Bresnahan (BBB) scale was used to evaluate the motor function in each group 1, 3, 7, 14, 21 and 28 days after injection. After behavioral assessment 3 days after injection, the protein expressions of ReIB, p52, phosphorylated (p)-ReIB and p-p52 in the spinal cord tissues were detected by Western blotting, and the expressions of anti-inflammatory cytokine and neurotrophic factor in the spinal cord tissues were detected by ELISA. After behavioral assessment 14 days after injection, immunofluorescent staining was performed to detect the expressions of neuronal nuclear antigen (NeuN), Syn and S100A10 in the spinal cord tissues. After behavioral assessment 28 days after injection, HE staining and uranyl acetate-lead citrate double staining were used to observe the pathological changes of the spinal cord under light microscope and electron microscope, respectively. Results:On 14, 21, and 28 days after injection, the BBB score in the SCI+rhMANF group was significantly higher than that in the SCI group and SCI+control group ( P<0.05). On 3 days after injection, the p-ReiB and p-p52 protein expressions in the SCI+rhMANF group (1.17±0.02 and 1.00±0.07) were significantly higher than those in the SCI group (0.74±0.01 and 0.42±0.11) and SCI+control group (0.79±0.00 and 0.64±0.02, P<0.05); the SCI+rhMANF group had significantly increased interleukin (IL)-4, IL-10, IL-13, neurotrophin-3, transforming growth factor-β and granulocyte colony-stimulating factor expressions ([217.58±16.06] pg/mg, [276.53±15.00]) pg/mg, [178.88±7.03] pg/mg, [172.61±16.43] pg/mg, [241.00±15.80] pg/mg, and [166.63±14.61] pg/mg) compared with the SCI group ([132.15±18.86] pg/mg, [173.48±18.24] pg/mg, [109.01±3.79] pg/mg, [104.64±18.21] pg/mg, [138.09±9.93] pg/mg, and [91.26±11.09] pg/mg), and SCI+control group ([137.80±27.70] pg/mg, [185.78±19.20] pg/mg, [112.44±13.51] pg/mg, [93.13±22.09] pg/mg, [159.48±32.50] pg/mg, and [112.67±18.32] pg/mg, P<0.05). On 14 days after injection, the immunofluorescent staining intensities of NeuN/S100A10, NeuN/Syn in the SCI+rhMANF group (2.51±0.24/2.85±0.27 and 2.48±0.35/1.92±0.32) were significantly higher than those in the SCI group (0.99±0.11/1.00±0.18 and 1.00±0.19/1.00±0.08) and SCI+control group (1.39±0.09/0.93±0.20 and 1.26±0.35/0.94±0.19, P<0.05). Light microscopy showed that the spinal cord nerve tissues in the SCI group and SCI+control group had loose structure, with edema and vacuolar degeneration; those in the sham-operated group and SCI+rhMANF group had dense structure, with round and cone-shaped neurons and large and round nucleus, and without vacuolar degeneration. Transmission electron microscopy showed intact structure of myelin sheath and axon in the sham-operated group, loose and shrunked spinal cord nerve cells (chromatin condensation, and cell membrane bleb formation) in the SCI group and SCI+control group, and relatively complete cell structure in the SCI+rhMANF group. Conclusion:The rhMANF can activate ReIB/P52 nuclear translocation phosphorylation, up-regulate the anti-inflammatory factor and neurotrophic factor expressions, induce the A2 astrocyte polarization, and promote the synaptic growth and spinal cord injury recovery.

Objective:To investigate the relationship between the level of angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) in the uterine fluid and the thickness of endometrium in infertile women with chronic endometritis.Methods:A case-control study was conducted to select 122 patients who underwent hysteroscopy and endometrial tissue biopsy at Assisted Reproduction Center, Taiyuan Central Hospital due to infertility from March 2023 to January 2024 as the study subjects. According to the results of hysteroscopy and endometrial tissue biopsy, the patients were divided into 52 cases in the infertility group with normal endometrium (NE infertility group) and the chronic endometritis combined with infertility group (CE infertility group) with 70 cases. Enzyme-linked immunosorbent assay was used to detect the level of AT1-AA in uterine fluid of the two groups. General clinical data, AT1-AA absorbance value of uterine fluid and uterine related indexes of the two groups were analyzed, and the correlations between AT1-AA level and the variation of indexes were analyzed.Results:Gravidity (median: 1 vs 1; Z=7.029, P=0.030) and parity (median: 0 vs 0; Z=12.258, P=0.002) in CE infertility group were higher than those in NE infertility group. There was AT1-AA in the uterine fluid, and the level of AT1-AA in CE infertility group was significantly higher than that in NE infertility group (median: 2.07 vs 1.44; Z=3.099, P=0.029). The endometrial thickness of CE infertility group was lower than that of NE infertility group (median: 6.0 vs 7.0 mm; Z=-2.179, P=0.029), and there were no statistical differences in other indexes between the two groups (all P>0.05). Further correlation analysis showed that there were no correlation between the level of AT1-AA in uterine fluid and parity, endometrial thickness, gravidity in NE infertility group (all P>0.05). However, the level of AT1-AA in uterine fluid of CE infertility group was positively correlated with parity (Spearman′s r=0.339, P=0.004), and negatively correlated with endometrial thickness (Spearman′s r=-0.499, P<0.001), but not correlated with gravidity ( P>0.05). Conclusions:AT1-AA is present in the uterine fluid of infertile women. The elevated level of AT1-AA in uterine fluid of infertile women with CE is related to the thinning of the endometrium.

objective:Thirty-three batches of Baohe Pill were subjected to quality analysis and exploratory study based on the test results.Methods:According to the methods in Chinese Pharmacopoeia,2020 Edition,Part Ⅰ and Ⅳ,the full-item chemical tests were conducted on Baohe Pill,and the exploratory study on the identification(2)method of Baohe Pill was conducted based on the method of Forsythia identification(2)in Chinese Pharmaco-poeia,2020 Edition,Part Ⅰ.Results:All the tested items in the 33 batches of samples were qualified,and the exploratory study on Baohe Pill based on the Forsythia herb also yielded satisfactory results.Conclusion:The qual-ity of Baohe Pill produced by various manufacturers can meet the requirements of Chinese Pharmacopoeia,ensuring the safe and effective use of drugs by the people.Through more extensive and thorough investigation,it is proposed to explore whether the identification(2)method of Baohe Pill in Chinese Pharmacopoeia needs to be optimized.

objective:Thirty-three batches of Baohe Pill were subjected to quality analysis and exploratory study based on the test results.Methods:According to the methods in Chinese Pharmacopoeia,2020 Edition,Part Ⅰ and Ⅳ,the full-item chemical tests were conducted on Baohe Pill,and the exploratory study on the identification(2)method of Baohe Pill was conducted based on the method of Forsythia identification(2)in Chinese Pharmaco-poeia,2020 Edition,Part Ⅰ.Results:All the tested items in the 33 batches of samples were qualified,and the exploratory study on Baohe Pill based on the Forsythia herb also yielded satisfactory results.Conclusion:The qual-ity of Baohe Pill produced by various manufacturers can meet the requirements of Chinese Pharmacopoeia,ensuring the safe and effective use of drugs by the people.Through more extensive and thorough investigation,it is proposed to explore whether the identification(2)method of Baohe Pill in Chinese Pharmacopoeia needs to be optimized.

Objective:To investigate the mechanism of recombinant human mesencephalic astrocyte-derived neurotrophic factor (rhMANF) in spinal cord injury (SCI) repair promoted by A2 reactive astrocyte polarization.Methods:One hundred and twenty female SPF SD rats were randomly divided into sham-operated group, SCI group, SCI+control group and SCI+rhMANF group ( n=30 in each group). SCI models were prepared by heavy drop method in the later 3 groups, and 10 μL sterile saline or 10 μL sterile saline+5 μg rhMANF were injected intrathecally in the later 2 groups 30 min after modeling. Basso-Beattie-Bresnahan (BBB) scale was used to evaluate the motor function in each group 1, 3, 7, 14, 21 and 28 days after injection. After behavioral assessment 3 days after injection, the protein expressions of ReIB, p52, phosphorylated (p)-ReIB and p-p52 in the spinal cord tissues were detected by Western blotting, and the expressions of anti-inflammatory cytokine and neurotrophic factor in the spinal cord tissues were detected by ELISA. After behavioral assessment 14 days after injection, immunofluorescent staining was performed to detect the expressions of neuronal nuclear antigen (NeuN), Syn and S100A10 in the spinal cord tissues. After behavioral assessment 28 days after injection, HE staining and uranyl acetate-lead citrate double staining were used to observe the pathological changes of the spinal cord under light microscope and electron microscope, respectively. Results:On 14, 21, and 28 days after injection, the BBB score in the SCI+rhMANF group was significantly higher than that in the SCI group and SCI+control group ( P<0.05). On 3 days after injection, the p-ReiB and p-p52 protein expressions in the SCI+rhMANF group (1.17±0.02 and 1.00±0.07) were significantly higher than those in the SCI group (0.74±0.01 and 0.42±0.11) and SCI+control group (0.79±0.00 and 0.64±0.02, P<0.05); the SCI+rhMANF group had significantly increased interleukin (IL)-4, IL-10, IL-13, neurotrophin-3, transforming growth factor-β and granulocyte colony-stimulating factor expressions ([217.58±16.06] pg/mg, [276.53±15.00]) pg/mg, [178.88±7.03] pg/mg, [172.61±16.43] pg/mg, [241.00±15.80] pg/mg, and [166.63±14.61] pg/mg) compared with the SCI group ([132.15±18.86] pg/mg, [173.48±18.24] pg/mg, [109.01±3.79] pg/mg, [104.64±18.21] pg/mg, [138.09±9.93] pg/mg, and [91.26±11.09] pg/mg), and SCI+control group ([137.80±27.70] pg/mg, [185.78±19.20] pg/mg, [112.44±13.51] pg/mg, [93.13±22.09] pg/mg, [159.48±32.50] pg/mg, and [112.67±18.32] pg/mg, P<0.05). On 14 days after injection, the immunofluorescent staining intensities of NeuN/S100A10, NeuN/Syn in the SCI+rhMANF group (2.51±0.24/2.85±0.27 and 2.48±0.35/1.92±0.32) were significantly higher than those in the SCI group (0.99±0.11/1.00±0.18 and 1.00±0.19/1.00±0.08) and SCI+control group (1.39±0.09/0.93±0.20 and 1.26±0.35/0.94±0.19, P<0.05). Light microscopy showed that the spinal cord nerve tissues in the SCI group and SCI+control group had loose structure, with edema and vacuolar degeneration; those in the sham-operated group and SCI+rhMANF group had dense structure, with round and cone-shaped neurons and large and round nucleus, and without vacuolar degeneration. Transmission electron microscopy showed intact structure of myelin sheath and axon in the sham-operated group, loose and shrunked spinal cord nerve cells (chromatin condensation, and cell membrane bleb formation) in the SCI group and SCI+control group, and relatively complete cell structure in the SCI+rhMANF group. Conclusion:The rhMANF can activate ReIB/P52 nuclear translocation phosphorylation, up-regulate the anti-inflammatory factor and neurotrophic factor expressions, induce the A2 astrocyte polarization, and promote the synaptic growth and spinal cord injury recovery.

Objective:To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses.Methods:This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio ( OR) values were used as indicators. Results:A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results ( P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95% CI: 1.020-1.069, P<0.001) and OR=1.170 (95% CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation ( SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment ( OR=1.020, 95% CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion:This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

Objective:To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses.Methods:This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio ( OR) values were used as indicators. Results:A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results ( P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95% CI: 1.020-1.069, P<0.001) and OR=1.170 (95% CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation ( SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment ( OR=1.020, 95% CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion:This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

Objective:To investigate the presence of angiotensin Ⅱ type 1 receptor autoantibodies (AT1-AA) in follicular fluid, and to investigate the correlation between AT1-AA levels and follicular development in follicular fluid of infertile patients with polycystic ovary syndrome (PCOS).Methods:A case-control study was conducted on 182 infertile patients who underwent in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) at the Center for Reproductive Medicine of Taiyuan Central Hospital from June 2021 to October 2022. There were 80 cases in the fallopian tube factor group (tubal factor group) and 102 cases in PCOS infertility group (PCOS group). Univariate analysis was performed for the general data, ovulation induction indexes and embryonic laboratory indexes of the two groups. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of AT1-AA in follicular fluid on the day of oocyte retrieval. Pearson or Spearman was used to analyze the correlation between AT1-AA level and follicle development indexes, and multiple linear regression was used to adjust for interfering factors to analyze the correlation between AT1-AA level and embryonic laboratory indicators. Results:Body mass index [BMI, (25.29±3.25) kg/m 2], antral follicle count [AFC, 24.00 (17.00, 24.00)], basal serum teststerone [0.50 (0.36, 0.79) μg/L] and anti-Müllerian hormone [AMH, 4.92 (2.57, 8.28) μg/L] in PCOS group were significantly higher than those in tubal factor group [(23.01±2.92) kg/m 2, P<0.001; 15.00 (10.25, 19.00), P<0.001; 0.38 (0.20, 0.59) μg/L, P=0.019; 3.06 (2.19, 4.89) μg/L, P=0.006]. Moreover, the AT1-AA P/N value in follicular fluid in PCOS group [4.24 (2.07, 8.89)] was significantly higher than that in tubal factor group [2.96 (1.86, 4.84), P=0.027]. In addition, the age of menarche in PCOS group [13.00 (12.00, 14.00) years] was earlier than that in tubal factor group [14.00 (13.00, 15.00) years, P=0.007]. Prolactin level [12.09 (9.65, 16.64) μg/L] was lower than that of tubal factor group [16.27 (12.86, 20.94) μg/L, P=0.002], and there were no statistical differences in other indexes between the two groups (all P>0.05). Correlation analysis showed that the level of AT1-AA in follicular fluid of PCOS patients was negatively correlated with oocyte retrieval rate ( r=-0.159, P=0.019). The results of multiple linear regression analysis showed that AT1-AA level in follicular fluid was negatively correlated with oocyte retrieval rate ( β=-0.598, P=0.028) and normal fertilization rate ( β=-0.527, P=0.022) after adjusting for confounding factors. Conclusion:The level of AT1-AA in follicular fluid in PCOS patients is significantly higher than that in patients with tubal infertility, and is negatively correlated with oocyte retrieval rate and normal fertilization rate.