Alzheimer's disease (AD) is the leading cause of dementia, and no effective treatment has been developed for it thus far. Recently, the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions. Accordingly, the potential therapeutic effect of pterostilbene (PTS) on AD has been demonstrated in multiple in vivo and in vitro experiments. In this study, we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD. Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms, including anti-oxidative damage, anti-neuroinflammation, anti-apoptosis, cholinesterase activity inhibition, attenuation of β-amyloid deposition, and tau protein hyperphosphorylation. Moreover, PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha (PPAR-α), monoamine oxidase B (MAO-B), silent information regulator sirtuin 1 (SIRT1), and phosphodiesterase 4A (PDE4A). Furthermore, to further elucidate the potential therapeutic mechanisms of PTS in AD, we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins, and the obtained binding energies ranged from -2.83 to -5.14 kJ/mol, indicating that these proteins exhibit good binding ability with PTS. Network pharmacology analysis revealed multiple potential mechanisms of action for PTS in AD. In summary, by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD, it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD, either using PTS or other developed drug interventions.

Adverse drug reactions (ADRs) significantly impact clinical medication safety. The timely identification and prediction of ADRs rely on the efficient analysis of real-world data, such as electronic health records, social media, and spontaneous reporting databases. In recent years, the rapid advancement of artificial intelligence, particularly large language models, in natural language processing, causal reasoning, and complex data mining has provided new technological means for real-time ADRs monitoring and individualized prediction. This paper summarizes the latest research achievements in AI-driven ADRs monitoring. Focusing on diverse data sources, including structured databases and electronic health records, it elaborates on the advantages andchallenges of AI in ADRs event extraction, relationship identification, causal analysis, and risk prediction. The aim is to provide a theoretical reference for constructing more intelligent and efficient ADRs monitoring systems.

Objective:To analyze the results of prenatal diagnosis and outcome of pregnancy for women with a high risk for fetal aneuploidies.Methods:A total of 747 cases of prenatal diagnosis by amniocentesis due to high risks by non-invasive prenatal testing (NIPT) were selected from January 2015 to March 2022 in the Drum Tower Hospital Affiliated to Nanjing University Medical School. The amniotic fluid samples were subjected to chromosomal karyotyping and/or chromosomal microarray analysis. All cases were followed up by searching the birth information or telephone calls, and the results were recorded. 2 test or F test were used for comparing the difference between the groups.Results:Among the 747 pregnant women with a high risk by NIPT, 387 were true positives, and the overall positive predictive value (PPV) was 51.81%. The PPVs for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13) and sex chromosome aneuploidies (SCA) were 80.24% (199/248), 60% (48/80), 14% (7/50) and 38.97% (106/272), respectively. The PPV for T21 was significantly higher than T18 and T13 ( χ2= 85.216, P<0.0001). The PPV for other chromosomal aneuploidies and copy number variations (CNVs) were 11.11% (5/45) and 40.74% (22/52), respectively. The PPV for increased X chromosomes was significantly higher than X chromosome decreases (64.29% vs. 22.22%, χ2= 5.530, P<0.05). The overall PPV for elder women (≥ 35 years old) was significantly higher than younger women (69.35% vs. 42.39%, χ2= 49.440, P<0.0001). For T21 and T18, the PPV of Z ≥ 10 group was significantly higher than that for 3 ≤ Z < 5 group or 5 ≤ Z < 10 group ( P<0.05). Among 52 cases with a high risk for CNVs, the PPV for the ≤ 5 Mb group was significantly higher than the 5 Mb < CNVs < 10 Mb or > 10 Mb groups (60% vs. 30%和60% vs. 23.53%, P<0.05). Among the 387 true positive cases, 322 had opted for induced labor, 53 had delivered with no abnormal growth and development, and 12 were lost during the follow-up. Conclusion:The PPVs for common chromosomal aneuploidies are related to the age and Z value of the pregnant women, which were higher in the elder group and higher Z value group. In addition, the PPV is associated with high risk types. The PPV for T21 was higher than T18 and T13, and that for 45, X was lower than 47, XXX, 47, XYY or 47, XXY syndrome. NIPT therefore has relatively high PPVs for the identification of chromosomal CNVs.

Objective:To investigate the influence of maternal autoimmune diseases and anticoagulants, including low-molecular-weight heparin (LMWH) and aspirin, on the fetal fraction of maternal plasma cell-free DNA of non-invasive prenatal testing (NIPT).Methods:A prospective cohort study was conducted on women with singleton pregnancies receiving NIPT in the Nanjing Drum Tower Hospital from March 2021 to July 2022. NIPT was carried out using a polymerase chain reaction (PCR)-free amplification platform. In this study, four types of maternal autoimmune diseases, which were antiphospholipid syndrome, undifferentiated connective tissue disease, Sj?gren's syndrome, and systemic lupus erythematosus (SLE), and two anticoagulants, LMWH and aspirin, were studied. Univariate and multivariate linear regression models were used to analyze the factors influencing fetal fraction of maternal plasma cell-free DNA.Results:A total of 4 102 singleton pregnant women were enrolled in the prospective cohort, and 3 948 were finally included after excluding the cases with unclear dosing time of LMWH or aspirin, other autoimmune diseases, conceiving through ovulation induction alone, and having true positive or failed NIPT result. There were 96 cases with antiphospholipid syndrome, 35 with undifferentiated connective tissue disease, 34 with Sj?gren's syndrome, and 18 with SLE. A total of 108 patients only received LMWH treatment, 121 only received aspirin treatment, and 113 received both LMWH and aspirin treatment. Univariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.423), conceived by assisted reproductive technology ( B=－0.803), male fetus ( B=－0.458), undifferentiated connective tissue disease ( B=1.774), and SLE ( B=3.467) had influence on the fetal fraction (all P<0.05). Multivariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.415), conceived by assisted reproductive technology ( B=－0.585), male fetus ( B=－0.322), SLE ( B=3.347) and undifferentiated connective tissue disease ( B=1.336) were factors influencing fetal fraction (all P<0.05). Conclusions:Maternal use of LMWH or aspirin does not affect fetal fraction when performing NIPT on a PCR-free amplification platform, but undifferentiated connective tissue disease and SLE are the influencing factors. Therefore, pregnant women should be informed before the NIPT that the fetal fraction of maternal plasma cell-free DNA may be affected by maternal autoimmune diseases.

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

OBJECTIVE: To explore the genetic etiology and related factors in 1 065 women with spontaneous abortions. METHODS: All patients have presented at the Center of Prenatal Diagnosis of Nanjing Drum Tower Hospital from January 2018 to December 2021. Chorionic villi and fetal skin samples were collected, and the genomic DNA was assayed by chromosomal microarray analysis (CMA). For 10 couples with recurrent spontaneous abortions but normal CMA results for abortive tissues, non-in vitro fertilization-embryo transfer (IVF-ET) pregnancies and no previous history of live births and no structural abnormalities of the uterus, peripheral venous blood samples were collected. Genomic DNA was subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing and bioinformatics analysis. Multifactorial unconditional logistic regression analysis was carried out to analyze the factors that may affect chromosomal abnormality in spontaneous abortions, such as the age of the couple, number of previous spontaneous abortions, IVF-ET pregnancy and history of live birth. The incidence of chromosomal aneuploidies in spontaneous abortions during the first trimester was compared in young or advanced-aged patients by chi-square test for liner trend. RESULTS: Among the 1 065 spontaneous abortion patients, 570 cases (53.5%) of chromosomal abnormalities were detected in spontaneous abortion tissues, which included 489 cases (45.9%) of chromosomal aneuploidies and 36 cases (3.4%) of pathogenic/likely pathogenic copy number variations (CNVs). Trio-WES results have revealed one homozygote variant and one compound heterozygote variants in two pedigrees, both of which were inherited from the parents. One likely pathogenic variant was detected in the patient from two pedigrees. Multifactorial unconditional Logistic regression analysis suggested that age of patient was an independent risk factor of chromosome abnormalities (OR = 1.122, 95%CI: 1.069-1.177, P < 0.001), the number of previous abortions and IVF-ET pregnancy were independent protective factors for chromosomal abnormalities (OR = 0.791, 0.648; 95%CI: 0.682-0.916, 0.500-0.840; P = 0.002, 0.001), whilst the age of husband and history of live birth were not (P > 0.05). The incidence of aneuploidies in the abortive tissues has decreased with the number of previous spontaneous abortions in young patients (χ² = 18.051, P < 0.001), but was not significantly correlated with the number of previous spontaneous abortions in advanced-aged patients with spontaneous abortions (P > 0.05). CONCLUSION Chromosomal aneuploidy is the main genetic factor for spontaneous abortion, though CNVs and genetic variants may also underlie its genetic etiology. The age of patients, number of previous abortions and IVF-ET pregnancy are closely associated with chromosome abnormalities in abortive tissues.
Pregnancy ; Humans ; Female ; Aged ; Abortion, Spontaneous/genetics* ; DNA Copy Number Variations ; Chromosome Aberrations ; Chromosome Disorders/genetics* ; Aneuploidy ; Abortion, Habitual/genetics*

Myocardial ischemia (MI) causes somatic referred pain and sympathetic hyperactivity, and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear. Here, in a rat model, we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back, but also elicited sympathetic sprouting in the skin of the referred area and C8-T6 dorsal root ganglia, and increased cardiac sympathetic tone, indicating sympathetic-sensory coupling. Moreover, intensifying referred hyperalgesic inputs with noxious mechanical, thermal, and electro-stimulation (ES) of the forearm augmented sympathetic hyperactivity and regulated cardiac function, whereas deafferentation of the left brachial plexus diminished sympathoexcitation. Intradermal injection of the α₂ adrenoceptor (α₂AR) antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES. Overall, these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α₂AR-mediated sympathetic-sensory coupling.
Animals ; Ganglia, Spinal ; Hyperalgesia/etiology* ; Myocardial Ischemia/complications* ; Pain, Referred/complications* ; Rats ; Sympathetic Nervous System

Objective:To explore the clinical effect of nerve-containing free latissimus dorsi myocutaneous flap in emergency treatment to repair the severe wound of the upper limb and restore the function of elbow flexion or extension.Methods:Retrospective analysis of the clinical data of patients with upper limb composite tissue defects treated in the Department of Joint Trauma Orthopedics of the Yidu Central Hospital of Weifang from March 2013 to November 2019, all of whom were repaired with nerve-containing free latissimus dorsi myocutaneous flap in an emergency. The patients were followed up for 12-24 months, and the patient’s satisfaction with the myocutaneous flap was investigated by questionnaire. The upper limb motor nerve function was evaluated by the upper limb function evaluation standard of the Chinese Society of Hand Surgery. The Mayo Elbow Performance Score was used to evaluate the effect of elbow repair. At 12 months after the operation, the flexion and extension of the elbow joint on the affected side and the healthy side, and the pronation angle and supination angle of the forearm were measured. Observe the shape and function of the donor area. SPSS 23.0 software was used for statistical analysis. Measurement data conforming to normal distribution were expressed as Mean±SD. An independent sample t-test was used to compare the differences in flexion and extension of the elbow between the affected side and the healthy side and the pronation and supination angles of the forearm. The difference is statistically significant if the P value is less than 0.05. Results:A total of 21 cases were included, including 15 males and 6 females. The age ranged from 18 to 60 years old, with an average of 37 years old. Causes of injury: traffic injury in 14 cases, machine injury in 7 cases. All of them were severe composite tissue defects of the upper limb, accompanied by elbow flexion or elbow extension function damage. The area of soft tissue defect is 15 cm × 6 cm-33 cm × 12 cm, and the area of the myocutaneous flap is 17 cm × 8 cm-35 cm × 15 cm. Time from injury to operation: 2-5 h. All the myocutaneous flaps of 21 patients survived. The patients were followed up for 12-24 months. The satisfaction rate of patients with myocutaneous flap healing was 100%(21/21); the satisfaction rate of morphology was 100% (21/21); the satisfaction rate of temperature was 90.48% (19/21); the satisfaction rate of sensation was 85.71%(18/21); the satisfaction rate of function was 95.24% (20/21). Motor nerve function examination and evaluation grading, 12 cases M3+ , 8 cases M3, and 1 case M2. The Mayo Elbow Performance Score, excellent in 11 cases, good in 8 cases, fair in 2 cases. Twelve months after the operation, the elbow flexion, extension, forearm pronation angle, and supination angle of the affected side and the healthy side were compared (134.73°±7.41°, 6.28°±2.16°, 78.59°±3.72°, 79.28°±3.59° respectively for the affected side and 139.37°±9.13°, 5.91°±1.95°, 80.26°±3.94°, 81.02°±3.81° for the healthy side). There was no statistical significance between the data ( t=1.81, 0.58, 1.41, 1.52; P=0.078, 0.563, 0.166, 0.136). There was no obvious scar contracture in the skin grafting area of the donor area, and there was no significant effect on the shape and function. Conclusions:Latissimus dorsi myocutaneous flap for emergency repair of severe tissue defects of the upper limb not only covers the defect wound but also reconstructs the function of the affected limb. It has the advantage that other myocutaneous flaps cannot replace and effectively shortens the recovery cycle of patients. It is one of the effective method for emergency repair of severe trauma of the upper limb with elbow function injury.

Objective:To explore the clinical effect of nerve-containing free latissimus dorsi myocutaneous flap in emergency treatment to repair the severe wound of the upper limb and restore the function of elbow flexion or extension.Methods:Retrospective analysis of the clinical data of patients with upper limb composite tissue defects treated in the Department of Joint Trauma Orthopedics of the Yidu Central Hospital of Weifang from March 2013 to November 2019, all of whom were repaired with nerve-containing free latissimus dorsi myocutaneous flap in an emergency. The patients were followed up for 12-24 months, and the patient’s satisfaction with the myocutaneous flap was investigated by questionnaire. The upper limb motor nerve function was evaluated by the upper limb function evaluation standard of the Chinese Society of Hand Surgery. The Mayo Elbow Performance Score was used to evaluate the effect of elbow repair. At 12 months after the operation, the flexion and extension of the elbow joint on the affected side and the healthy side, and the pronation angle and supination angle of the forearm were measured. Observe the shape and function of the donor area. SPSS 23.0 software was used for statistical analysis. Measurement data conforming to normal distribution were expressed as Mean±SD. An independent sample t-test was used to compare the differences in flexion and extension of the elbow between the affected side and the healthy side and the pronation and supination angles of the forearm. The difference is statistically significant if the P value is less than 0.05. Results:A total of 21 cases were included, including 15 males and 6 females. The age ranged from 18 to 60 years old, with an average of 37 years old. Causes of injury: traffic injury in 14 cases, machine injury in 7 cases. All of them were severe composite tissue defects of the upper limb, accompanied by elbow flexion or elbow extension function damage. The area of soft tissue defect is 15 cm × 6 cm-33 cm × 12 cm, and the area of the myocutaneous flap is 17 cm × 8 cm-35 cm × 15 cm. Time from injury to operation: 2-5 h. All the myocutaneous flaps of 21 patients survived. The patients were followed up for 12-24 months. The satisfaction rate of patients with myocutaneous flap healing was 100%(21/21); the satisfaction rate of morphology was 100% (21/21); the satisfaction rate of temperature was 90.48% (19/21); the satisfaction rate of sensation was 85.71%(18/21); the satisfaction rate of function was 95.24% (20/21). Motor nerve function examination and evaluation grading, 12 cases M3+ , 8 cases M3, and 1 case M2. The Mayo Elbow Performance Score, excellent in 11 cases, good in 8 cases, fair in 2 cases. Twelve months after the operation, the elbow flexion, extension, forearm pronation angle, and supination angle of the affected side and the healthy side were compared (134.73°±7.41°, 6.28°±2.16°, 78.59°±3.72°, 79.28°±3.59° respectively for the affected side and 139.37°±9.13°, 5.91°±1.95°, 80.26°±3.94°, 81.02°±3.81° for the healthy side). There was no statistical significance between the data ( t=1.81, 0.58, 1.41, 1.52; P=0.078, 0.563, 0.166, 0.136). There was no obvious scar contracture in the skin grafting area of the donor area, and there was no significant effect on the shape and function. Conclusions:Latissimus dorsi myocutaneous flap for emergency repair of severe tissue defects of the upper limb not only covers the defect wound but also reconstructs the function of the affected limb. It has the advantage that other myocutaneous flaps cannot replace and effectively shortens the recovery cycle of patients. It is one of the effective method for emergency repair of severe trauma of the upper limb with elbow function injury.

OBJECTIVE: To analyze the cause and pregnancy outcome for non-reportable cell-free DNA (cfDNA) results during non-invasive prenatal testing (NIPT). METHODS: cfDNA was extracted from maternal plasma from 5898 singleton pregnancies at 12 to 22 gestational weeks and underwent NIPT with strict quality control standards. For those with sub-standard results, redraw or invasive prenatal procedures were recommended. RESULTS: Among the 5898 cases, 32 have failed for the initial NIPT, including 17 cases with substandard cffDNA%, 10 cases with data fluctuation after twice library constructing and sequencing, and 5 cases with unidentifiable sex chromosome abnormalities. For these 32 cases, 2 directly underwent amniocentesis, and karyotyping analysis showed both were normal. Six of the 30 redrawn cases finally turned out to be nonreportable. The final nonreportable rate was therefore 0.1% (8/5898). Of the redrawn cases, 1 trisomy 21, 1 trisomy 18 and 1 trisomy 13 high risk-cases were identified, which were all confirmed to be false positive. Among the 6 nonreportable cases, 2 women underwent invasive prenatal testing, and 1 was found to have a normal fetal karyotype, while another was found to have an abnormal karyotype of mos45,X[32]/46,XY[18]. The other 4 nonreportable cases who did not accept invasive prenatal testing have all reported normal child development at follow-up. CONCLUSION The main reason for nonreportable NIPT results was low cffDNA%. The high success rate of the redrawn cases has effectively increased the overall NIPT success rate and reduced the number of the cases necessitating invasive prenatal diagnosis. The initially nonreportable women may consider retesting after careful counseling with informed consent.
Aneuploidy ; Child ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Prenatal Diagnosis ; Trisomy ; Trisomy 18 Syndrome/genetics*