The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

This article reports the diagnosis and treatment process of a patient with meningeal carcinomatosi.An el-derly male presented with 30 days of headaches,nausea,and vomiting,which progressively worsened over the past 9 days.Cranial imaging indicated hydrocephalus and ventricular dilatation.Metagenomic next-generation sequencing,com-bined with chromosomal copy number variation(CNV)analysis of human sequences in the cerebrospinal fluid(CSF),re-vealed the absence of pathogens but the presence of abnormal aneuploidy in human sequences,strongly suggesting malig-nancy.Subsequently,an Ommaya reservoir was placed in the patient's ventricles,and repeated CSF cytology examina-tions revealed atypical cells.Based on clinical presentation,CSF cytology,and CNV analysis,the diagnosis of meningeal carcinomatosis was confirmed.mNGS-CNV analysis is of great significance for the diagnosis of meningeal carcinomatosis.By reviewing the diagnosis and treatment process of this patient,reference can be provided for the diagnosis and treatment of meningeal carcinomatosi.

Objective:To study the clinical features of enlarged subarachnoid space (ESS) and its effects on brain parenchymal volume in preterm infants.Methods:From November 2014 to November 2021, a retrospective case-control study was performed on preterm infants admitted to neonatal intensive care unit of our hospital with gestational age (GA)<32 w and having brain MR imaging. At full-term of corrected GA, the superior sagittal sinus-cortical spacing (sinocortical width, SCW) was measured on brain MR imaging. The infants were assigned into ESS and non-ESS groups according to whether SCW was greater than 3.5 mm. Perinatal factors, preterm-related complications and the brain volumetric indices were compared between the two groups.Results:A total of 160 preterm infants with GA<32 w were included, 76 (47.5%) were in the ESS group, SCW:(4.48±1.47) mm, and 84 were in the non-ESS group, SCW: (2.49±0.68) mm. GA and birth weight (BW) of the ESS group were significantly smaller than the non-ESS group [(28.7±2.6) weeks vs.(29.8±2.5) weeks, (1 114±279)g vs. (1 208±290)g]( P<0.05). Small GA was an independent risk factor for the development of ESS in preterm infants with GA<32w ( OR=1.217,95% CI 1.017~1.457, P=0.032). On MR imaging, the ESS group had significantly higher total cranial cavity volume than the non-ESS group [(354.1±33.6)ml vs. (316.9±36.3) ml] ( P<0.05). No significant differences existed on head circumference, gray matter volume and white matter volume between the two groups ( P>0.05). Conclusions:ESS is common in premature infants and correlated with GA and BW. Small GA is an independent risk factor for ESS in preterm infants. ESS shows little effects on head circumference and brain parenchymal volume during early postnatal period.

Objective:To investigate the risk factors for textbook outcomes (TO) of intra-hepatic cholangiocarcinoma (ICC) after hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 155 ICC patients who underwent hepatectomy in the First Affiliated Hospital of Sun Yat-sen University from September 2014 to August 2019 were collected. There were 90 males and 65 females, aged 60(range, 26?82)years. Observation indicators: (1) treatment situations; (2) TO situations; (3) analysis of risk factors for postoperative TO. Follow-up was conducted using outpatient examination and telephone interview to detect postoperative sur-vival of patients up to October 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent samples t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test, Yates' calibration chi-square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. The univariate analysis was conducted using the corresponding statistical methods based on data type. The Logistic regression model was used for multivariate analysis. The receiver operating characteristic (ROC) curve was used for evaluating the diagnostic value of indicators (the optimal cut-off value). Results:(1) Treatment situations. Of the 155 patients, 46 cases underwent minor hepatectomy and 109 cases underwent major hepatectomy. Twenty-one of the 155 patients underwent combined bile duct reconstruction. Ninety-five of the 155 patients underwent lymph node dissection, including 41 cases with positive lymph node by postoperative histopathological examinations. The operation time and volume of intraoperative blood loss of the 155 patients were 250.0(range, 95.0?720.0)minutes and 300.0(range, 50.0?15 000.0)mL, respectively. The optimal cut-off values of the operation time and volume of intraoperative blood loss for TO calculated by ROC curve were 247.5 minutes and 325.0 mL, respectively. Of the 155 patients, 44 cases received intraoperative blood transfusion and 10 cases received postoperative blood transfusion (5 cases with intraoperative and postoperative blood transfusion). Seventy-four of the 155 patients had postoperative complications, including 39 cases with mild complications and 35 cases with serious complications. The total duration of hospital stay of the 155 patients was 19 (range, 8?77)days. (2) TO situations. Of the 155 patients, 150 cases achieved R 0 resection, 120 cases had no major postoperative complications, 106 cases had no perioperative blood transfusion, 79 cases had no prolonged duration of hospital stay, 152 cases had no death within postoperative 30 days and 150 cases had no readmission within 30 days after discharge. Of the 155 patients, 56 cases achieved postoperative TO, while 99 patients did not achieve TO. (3) Analysis of risk factors for postoperative TO. Results of univariate analysis showed that preoperative biliary drainage, preoperative Child-Pugh grading of liver function, preoperative asymp-tomatic leukocytosis, preoperative total bilirubin, preoperative alkaline phosphatase, preoperative CA19-9, preoperative CA125, operation time, volume of intraoperative blood loss, tumor diameter, pathological T staging and pathological N staging were related factors for preoperative TO of ICC patients undergoing hepatectomy ( χ2=4.31, 4.31, 4.38, 4.80, Z=?4.15, χ2=10.74, 15.44, 16.59, 27.53, 6.53, 6.77, 9.26, P<0.05). Bile duct reconstruction was also a related factor for postoperative TO of ICC patients ( P<0.05). Results of multivariate analysis showed that preoperative biliary drainage, preoperative asymptomatic leukocytosis, preoperative CA19-9 >35 U/mL, preoperative CA125 >35 U/mL and volume of intraoperative blood loss >325.0 mL were independent risk factors for postoperative TO of ICC patients undergoing hepatectomy ( odds ratio=74.77, 11.73, 2.40,4.86, 6.42, 95% confidence intervals as 1.80?113.39, 1.19?115.54, 1.04?5.53, 1.78?13.26, 2.41?17.11, P<0.05). Conclusions:Preoperative biliary drainage, preoperative asymptomatic leukocytosis, preoperative CA19-9 >35 U/mL, preoperative CA125 >35 U/mL and volume of intraoperative blood loss >325.0 mL are independent risk factors for postoperative TO of ICC patients undergoing hepatectomy.

Objective:To evaluate the efficacy of oral levothyroxine on abortion rate and preterm birth rate in pregnant women with thyroid autoimmunity (TAI) and normal thyroid function.Methods:The relevant studies of oral levothyroxine tablets in the treatment of TAI pregnant women were systematically searched in Pubmed, Cochrane, CBM, CNKI, VIP and Wanfang databases. The retrieval period was established until August 2020. Two researchers independently screened the literatures, extracted the data and evaluated the risk of bias in the included study. Meta-analysis was performed using Revman5.3 software.Results:1) Totally six eligible studies were all randomized controlled studies, involving 1427 patients. 2) Compared with control group, the meta-analysis suggests oral levothyroxine tablets cannot effectively reduce the preterm delivery rate and the abortion rate. 3) Further subgroup analysis of the data according to the natural pregnancy group and assisted reproduction group found that oral levothyroxine tablets in natural pregnancy women with TAI can effectively reduce the preterm delivery rate ( RR=0.54, 95% CI=0.31-0.95, P=0.03), but not reduce the abortion rate ( RR=0.86, 95% CI=0.69-1.06, P=0.15). However, oral levothyroxine tablets cannot reduce the abortion rate for TAI women conceived by reproductive technology ( RR=0.80, 95% CI=0.47-1.36, P=0.41). Conclusion:Oral levothyroxine tablets can effectively reduce the premature delivery rate of TAI women who are naturally pregnant, but it is not beneficial to reduce the abortion rate. There is only one study on TAI women who are pregnant with reproductive technology, so it is impossible to evaluate whether this population can benefit from taking levothyroxine tablets. In view of the above results, it is recommended that the two groups of patients be managed separately.

Objective:To evaluate the efficacy of oral levothyroxine on abortion rate and preterm birth rate in pregnant women with thyroid autoimmunity (TAI) and normal thyroid function.Methods:The relevant studies of oral levothyroxine tablets in the treatment of TAI pregnant women were systematically searched in Pubmed, Cochrane, CBM, CNKI, VIP and Wanfang databases. The retrieval period was established until August 2020. Two researchers independently screened the literatures, extracted the data and evaluated the risk of bias in the included study. Meta-analysis was performed using Revman5.3 software.Results:1) Totally six eligible studies were all randomized controlled studies, involving 1427 patients. 2) Compared with control group, the meta-analysis suggests oral levothyroxine tablets cannot effectively reduce the preterm delivery rate and the abortion rate. 3) Further subgroup analysis of the data according to the natural pregnancy group and assisted reproduction group found that oral levothyroxine tablets in natural pregnancy women with TAI can effectively reduce the preterm delivery rate ( RR=0.54, 95% CI=0.31-0.95, P=0.03), but not reduce the abortion rate ( RR=0.86, 95% CI=0.69-1.06, P=0.15). However, oral levothyroxine tablets cannot reduce the abortion rate for TAI women conceived by reproductive technology ( RR=0.80, 95% CI=0.47-1.36, P=0.41). Conclusion:Oral levothyroxine tablets can effectively reduce the premature delivery rate of TAI women who are naturally pregnant, but it is not beneficial to reduce the abortion rate. There is only one study on TAI women who are pregnant with reproductive technology, so it is impossible to evaluate whether this population can benefit from taking levothyroxine tablets. In view of the above results, it is recommended that the two groups of patients be managed separately.

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.
Animals ; Apoptosis ; Caspase 8/metabolism* ; GTPase-Activating Proteins/metabolism* ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*

The firstly successful birth in the world following the uterus transplantation brings new hope to the majority of infertility women with uterine factors, but due to the difficulty of the operation, the high risk, the low success rate, and ethical issues, it still faces many challenges, which has caused widespread concern. The research progress and ethical issues of uterine transplantation were reviewed in this paper.

The firstly successful birth in the world following the uterus transplantation brings new hope to the majority of infertility women with uterine factors, but due to the difficulty of the operation, the high risk, the low success rate, and ethical issues, it still faces many challenges, which has caused widespread concern. The research progress and ethical issues of uterine transplantation were reviewed in this paper.

Objective:To investigate the differences in polyunsaturated fatty acid metabolites in seminal plasma between normal group and low sperm motility group, and their relationship with sperm motility.Methods:Totally 581 human seminal plasmas collected from Guizhou Province were divided into normal group and low sperm motility group according to the motility rate. The metabolite products of 24 kinds of polyunsaturated fatty acids were detected by liquid phase tandem mass spectrometry/mass spectrometry (LC-MS/MS). Through the in vitro culture experiment of sperm, the culture supernatant was collected during the culture of the upstream screening sperm for 24 h, and the polyunsaturated fatty acid products with different differences detected in the different groups of seminal plasma were also verified by LC-MS/MS method. Results:Among the polyunsaturated fatty acid metabolites detected in seminal plasma, the concentrations of 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE) in the seminal plasma of the low sperm motility group were significantly different from those in the normal seminal plasma group ( P=0.001, P=0.033). In vitro culture experiments showed that the concentration of 9-HODE and 13-HODE in the culture medium increased significantly with the prolongation of culture time and the decrease of sperm motility rate ( P=0.003, P=0.035). Statistical analysis showed that the concentrations of 9-HODE and 13-HODE were significantly negatively correlated with sperm motility （ r=-0.91， P=0.045； r=-0.95， P=0.026）. Considering the sperm density factor in the analysis of polyunsaturated fatty acid metabolites and sperm motility in the seminal plasma of the population, the results showed that 9-HODE and 13-HODE were significantly higher in the low sperm motility group than in the normal group ( P<0.000 1). And there was a negative correlation ( r=-0.38) with the sperm motility rate ( P<0.000 1). Conclusion:9-HODE and 13-HODE are released into the culture medium and seminal plasma by sperm cell metabolism, which is a potential indicator of the degree of sperm membrane damage, which may be helpful in judging and detecting the asthenospermia.