Objective To clarify the effect of unilateral activation of the dopamine type I receptor medium-sized multi-spiny neurons(D1-MSN)in the dorsal striatum of mice on speed.Methods The transgenic animals were combined with optogenetic experiments to specifically activate the D1-MSN in the dorsal striatum of mice at different frequencies and to analyze the rotational behavior and speed of mice when stimulating the D1-MSN.Results Unilateral activation of D1-MSN induces contralateral rotational behavior in mice and either increases or decreases speed.The mechanisms by which different frequencies affect the speed of mice differently.As the frequency of stimulus increased,the contralateral rotational behavior of the mice increased.Unilateral stimulus of D1-MSN increased speed and induced contralateral rotational behavior,and the rotational behavior increased with increasing stimulus frequency.In the experiment where D1-MSN stimulus did not induce rotational behavior,it was found that 5 Hz stimulus still induced an increase in speed,but 15 Hz and 25 Hz stimulus did not induce an increase in speed.Further analysis of the pre-stimulus locomotor state of the mice showed that 5 Hz,15 Hz and 25 Hz stimulus increased speed when the average speed before stimulus was less than 5 cm/s.However,15 Hz stimulus decreased the speed when the average speed before stimulus was greater than 5 cm/s.Conclusion Unilateral activation of D1-MSN in the dorsal striatum modulates speed and induces contralateral rotational behavior in mice,and is related to the frequency of stimulus and the locomotor state of the mice before stimulus.

A case of a 51-year-old male presented with leukocytosis, lymphocytosis, and splenomegaly. Comprehensive diagnostic evaluations, including cytomorphology, flow cytometric immunophenotyping, and splenic pathology, confirmed the diagnosis of splenic diffuse red pulp small B-cell lymphoma (SDRPL). The patient tested was positive for TP53 mutation and demonstrated poor response to various chemotherapy regimens. During follow-up, the patient′s condition deteriorated. PET-CT revealed multiple metabolically active lymph nodes throughout the body. Peripheral blood smear revealed abnormal lymphocytes, which suggests potential high-grade transformation. Pathological examination of axillary lymph nodes indicated lymphoma cell infiltration, with positive expression of BCL-2, BCL-6, and C-MYC. Subsequent treatment with Zanubrutinib+Obinutuzumab+Bendamustine yielded suboptimal results. Chimeric antigen receptor T-cell immunotherapy (CAR-T) was subsequently administered, and after 9 months, minimal residual disease (MRD) evaluation was negative. SDRPL is a rare indolent B-cell lymphoma, and its diagnosis relies on splenic pathology. The abnormal lymphocytes exhibit characteristic villous projections, and monitoring morphological changes during follow-up can indicate disease progression, providing a basis for selecting appropriate treatment strategies.

X-linked adrenoleukodystrophy(X-ALD) is an inherited progressive neurometabolic disorder caused by mutations in the ATP-binding cassette subfamily D member 1(ABCD1) gene. The encoded ALD protein dysfunction leads to the accumulation of very-long-chain fatty acids(VLCFA). X-ALD is classified according to its clinical characteristics into childhood cerebral ALD, adolescent cerebral ALD, adult cerebral ALD, adrenomyeloneuropathy(AMN), pure adrenocortical insufficiency, and an asymptomatic phenotype, all of which can present with a variety of neurologic manifestations. In this study, we retrospectively analyzed the clinical manifestations, laboratory findings, genetic test results, and follow-up data of four patients with X-ALD, and investigated the clinical features and pathogenicity of the identified gene mutations. All four patients initially presented with adrenocortical insufficiency(Addison′s disease) and received glucocorticoid replacement therapy. Subsequently, all developed neurologic signs and symptoms with rapid progression. The final diagnosis was confirmed based on elevated VLCFA levels, brain magnetic resonance imaging(MRI) findings, and genetic analysis. Notably, a deletion mutation in Exon 10 of the ABCD1 gene was identified in one case for the first time. We report four cases of X-ALD presenting with adrenocortical insufficiency as the initial symptom, and briefly review the relevant literature to analyze the relationship between linical phenotypes and genetic loci, aiming to provide a reference for early diagnosis and treatment of the disease, and to reduce the risk of misdiagnosis and missed diagnosis.

Objective To clarify the effect of unilateral activation of the dopamine type I receptor medium-sized multi-spiny neurons(D1-MSN)in the dorsal striatum of mice on speed.Methods The transgenic animals were combined with optogenetic experiments to specifically activate the D1-MSN in the dorsal striatum of mice at different frequencies and to analyze the rotational behavior and speed of mice when stimulating the D1-MSN.Results Unilateral activation of D1-MSN induces contralateral rotational behavior in mice and either increases or decreases speed.The mechanisms by which different frequencies affect the speed of mice differently.As the frequency of stimulus increased,the contralateral rotational behavior of the mice increased.Unilateral stimulus of D1-MSN increased speed and induced contralateral rotational behavior,and the rotational behavior increased with increasing stimulus frequency.In the experiment where D1-MSN stimulus did not induce rotational behavior,it was found that 5 Hz stimulus still induced an increase in speed,but 15 Hz and 25 Hz stimulus did not induce an increase in speed.Further analysis of the pre-stimulus locomotor state of the mice showed that 5 Hz,15 Hz and 25 Hz stimulus increased speed when the average speed before stimulus was less than 5 cm/s.However,15 Hz stimulus decreased the speed when the average speed before stimulus was greater than 5 cm/s.Conclusion Unilateral activation of D1-MSN in the dorsal striatum modulates speed and induces contralateral rotational behavior in mice,and is related to the frequency of stimulus and the locomotor state of the mice before stimulus.

X-linked adrenoleukodystrophy(X-ALD) is an inherited progressive neurometabolic disorder caused by mutations in the ATP-binding cassette subfamily D member 1(ABCD1) gene. The encoded ALD protein dysfunction leads to the accumulation of very-long-chain fatty acids(VLCFA). X-ALD is classified according to its clinical characteristics into childhood cerebral ALD, adolescent cerebral ALD, adult cerebral ALD, adrenomyeloneuropathy(AMN), pure adrenocortical insufficiency, and an asymptomatic phenotype, all of which can present with a variety of neurologic manifestations. In this study, we retrospectively analyzed the clinical manifestations, laboratory findings, genetic test results, and follow-up data of four patients with X-ALD, and investigated the clinical features and pathogenicity of the identified gene mutations. All four patients initially presented with adrenocortical insufficiency(Addison′s disease) and received glucocorticoid replacement therapy. Subsequently, all developed neurologic signs and symptoms with rapid progression. The final diagnosis was confirmed based on elevated VLCFA levels, brain magnetic resonance imaging(MRI) findings, and genetic analysis. Notably, a deletion mutation in Exon 10 of the ABCD1 gene was identified in one case for the first time. We report four cases of X-ALD presenting with adrenocortical insufficiency as the initial symptom, and briefly review the relevant literature to analyze the relationship between linical phenotypes and genetic loci, aiming to provide a reference for early diagnosis and treatment of the disease, and to reduce the risk of misdiagnosis and missed diagnosis.

A case of a 51-year-old male presented with leukocytosis, lymphocytosis, and splenomegaly. Comprehensive diagnostic evaluations, including cytomorphology, flow cytometric immunophenotyping, and splenic pathology, confirmed the diagnosis of splenic diffuse red pulp small B-cell lymphoma (SDRPL). The patient tested was positive for TP53 mutation and demonstrated poor response to various chemotherapy regimens. During follow-up, the patient′s condition deteriorated. PET-CT revealed multiple metabolically active lymph nodes throughout the body. Peripheral blood smear revealed abnormal lymphocytes, which suggests potential high-grade transformation. Pathological examination of axillary lymph nodes indicated lymphoma cell infiltration, with positive expression of BCL-2, BCL-6, and C-MYC. Subsequent treatment with Zanubrutinib+Obinutuzumab+Bendamustine yielded suboptimal results. Chimeric antigen receptor T-cell immunotherapy (CAR-T) was subsequently administered, and after 9 months, minimal residual disease (MRD) evaluation was negative. SDRPL is a rare indolent B-cell lymphoma, and its diagnosis relies on splenic pathology. The abnormal lymphocytes exhibit characteristic villous projections, and monitoring morphological changes during follow-up can indicate disease progression, providing a basis for selecting appropriate treatment strategies.

Objective::This study investigates the efficacy of analyzing fetal heart rate (FHR) signals based on Artificial Intelligence to obtain a baseline calculation and identify accelerations/decelerations in the FHR through electronic fetal monitoring during labor.Methods::A total of 43,888 cardiotocograph(CTG) records of female patients in labor from January 2012 to December 2020 were collected from the NanFang Hospital of Southern Medical University. After filtering the data, 2341 FHR records were used for the study. The ObVue fetal monitoring system, manufactured by Lian-Med Technology Co. Ltd., was used to monitor the FHR signals for these pregnant women from the beginning of the first stage of labor to the end of delivery. Two obstetric experts together annotated the FHR signals in the system to determine the baseline as well as accelerations/decelerations of the FHR. Our cardiotocograph network (CTGNet) as well as traditional methods were then used to automatically analyze the baseline and acceleration/deceleration of the FHR signals. The results of calculations were compared with the annotations provided by the obstetric experts, and ten-fold cross-validation was applied to evaluate them. The root-mean-square difference (RMSD) between the baselines, acceleration F-measure (Acc.F-measure), deceleration F-measure (Dec.F-measure), coefficient of synthetic inconsistency (SI) and the morphological analysis discordance index (MADI) were used as evaluation metrics. The data were analyzed by using a paired t-test. Results::The proposed CTGNet was superior to the best traditional method, proposed by Mantel, in terms of the RMSD.BL (1.7935 ± 0.8099 vs. 2.0293 ± 0.9267, t=-3.55 , P=0.004), Acc.F-measure (86.8562 ± 10.9422 vs. 72.2367 ± 14.2096, t= 12.43, P <0.001), Dec.F-measure (72.1038 ± 33.2592 vs. 58.5040 ± 38.0276, t= 4.10, P <0.001), SI (34.8277±20.9595 vs. 54.8049 ± 25.0265, t=-9.39, P <0.001), and MADI (3.1741 ± 1.9901 vs. 3.7289 ± 2.7253, t= -2.74, P= 0.012). The proposed CTGNet thus had significant advantages over the best traditional method on all evaluation metrics. Conclusion::The proposed Artificial Intelligence-based method CTGNet delivers good performance in terms of the automatic analysis of FHR based on cardiotocograph data. It promises to be a key component of smart obstetrics systems of the future.

Objective::This study investigates the efficacy of analyzing fetal heart rate (FHR) signals based on Artificial Intelligence to obtain a baseline calculation and identify accelerations/decelerations in the FHR through electronic fetal monitoring during labor.Methods::A total of 43,888 cardiotocograph(CTG) records of female patients in labor from January 2012 to December 2020 were collected from the NanFang Hospital of Southern Medical University. After filtering the data, 2341 FHR records were used for the study. The ObVue fetal monitoring system, manufactured by Lian-Med Technology Co. Ltd., was used to monitor the FHR signals for these pregnant women from the beginning of the first stage of labor to the end of delivery. Two obstetric experts together annotated the FHR signals in the system to determine the baseline as well as accelerations/decelerations of the FHR. Our cardiotocograph network (CTGNet) as well as traditional methods were then used to automatically analyze the baseline and acceleration/deceleration of the FHR signals. The results of calculations were compared with the annotations provided by the obstetric experts, and ten-fold cross-validation was applied to evaluate them. The root-mean-square difference (RMSD) between the baselines, acceleration F-measure (Acc.F-measure), deceleration F-measure (Dec.F-measure), coefficient of synthetic inconsistency (SI) and the morphological analysis discordance index (MADI) were used as evaluation metrics. The data were analyzed by using a paired t-test. Results::The proposed CTGNet was superior to the best traditional method, proposed by Mantel, in terms of the RMSD.BL (1.7935 ± 0.8099 vs. 2.0293 ± 0.9267, t=-3.55 , P=0.004), Acc.F-measure (86.8562 ± 10.9422 vs. 72.2367 ± 14.2096, t= 12.43, P <0.001), Dec.F-measure (72.1038 ± 33.2592 vs. 58.5040 ± 38.0276, t= 4.10, P <0.001), SI (34.8277±20.9595 vs. 54.8049 ± 25.0265, t=-9.39, P <0.001), and MADI (3.1741 ± 1.9901 vs. 3.7289 ± 2.7253, t= -2.74, P= 0.012). The proposed CTGNet thus had significant advantages over the best traditional method on all evaluation metrics. Conclusion::The proposed Artificial Intelligence-based method CTGNet delivers good performance in terms of the automatic analysis of FHR based on cardiotocograph data. It promises to be a key component of smart obstetrics systems of the future.

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC

Objective:To observe the efficacy and safety of vitrectomy combined with submacular injection of tissue-type plasminogen activator (t-PA), gas filling and anti-VEGF drugs (multiple therapy) for thick submacular hemorrhage.Methods:A retrospective case study. From January 2014 to June 2018, 24 patients (24 eyes) with thick submacular hemorrhage who received multiple therapy at the Department of Ophthalmology of Peking University Third Hospital were included in the study. Among them, there were 15 males and 9 females with the average age of 69.05±8.86 years. The average submacular bleeding time was 17.15±10.30 days, the average bleeding area was 13.85±8.63 DD. Seventeen eyes showed hemorrhagic RPE detachment. The international standard visual acuity chart was used to BCVA examination, which was converted to logMAR visual acuity in statistics. The frequency domain OCT was used to measure the height of the foveal elevation. The average logMAR BCVA of the affected eye was 1.37±0.38. The average height of the macular fovea was 824.94±294.38 μm. All eyes underwent 23G or 25G vitrectomy. During the operation, 0.1-0.5 ml t-PA (10 μg/0.1 ml) was injected under the macula. The vitreous cavity was filled with 15% C 3F 8 after gas-liquid exchange in 13 eyes, and 11 eyes were filled with sterilized air. Eleven eyes were injected with anti-VEGF drugs at the end of the operation, and anti-VEGF drugs were given PRN treatment according to the activity of the lesion. The average follow-up time after treatment was 27.90±22.21 months. The absorption of bleeding under the macula, the improvement of vision, the occurrence of rebleeding and treatment-related complications were observed and recorded. The Wilcoxon rank sum test was performed to compare the BCVA and the height of foveal elevation before and after treatment. Results:One month after the treatment, the blood in the fovea of all affected eyes was cleared. At the last follow-up, the logMAR BCVA and macular foveal elevation were 0.82±0.28 and 253.88±71.75 μm, respectively. Compared with those before treatment, the difference was statistically significant ( Z=-3.727, -3.234; P<0.001, <0.001). The average intravitreal injection of anti-VEGF drugs was 1.08 times. During the operation, a tiny hole was formed in the center of the macula when t-PA was injected under the retina. Two eyes showed mild vitreous hemorrhage early after the operation. During the follow-up period, bleeding recurred in 2 eyes. Conclusions:Vitrectomy combined with submacular injection of t-PA, gas filling, and anti-VEGF drugs is an optimal combination for the treatment of thick submacular hemorrhage. It can effectively remove submacular hemorrhage, improve vision, reduce foveal elevation with good safety.