ObjectiveTo explore the possible mechanisms of Modified Shoutai Pill （寿胎丸加味方， MSP） in treating polycystic ovary syndrome （PCOS） with hyperandrogenism， insulin resistance， and miscarriage， focusing on inflammatory response and endometrial receptivity. MethodsThirty female SPF-grade SD rats with regular estrous cycles and in proestrus， and 15 male SPF-grade SD rats were housed together in a 2∶1 ratio at 18：00. At 8：00 next morning， rats showing abundant sperm and vaginal plugs were considered pregnant on the day 0.5. The 30 pregnant rats were randomly divided into three groups， normal group， model group， and MSP group， with 10 rats in each group. From day 0.5 to day 13.5 of pregnancy， the MSP group was given 26.6 g/（kg·d） of the MSP via gavage twice a day for 14 consecutive days. The normal group and the model group received 4 ml of normal saline daily. From day 7.5 to day 13.5 of pregnancy， the rats in the model group and MSP group were intraperitoneally injected with dihydrotestosterone （DHT） and insulin （INS） for 7 consecutive days to establish a PCOS model with hyperandrogenism， insulin resistance， and miscarriage. On day 13.5 of pregnancy， an oral glucose tolerance test （OGTT） was performed to measure blood glucose levels at 0， 30， 60， 90， and 120 minutes. On day 14.5， serum level of progesterone （P₄）， estradiol （E₂）， fasting insulin （FINS）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） were measured by ELISA. The insulin resistance index （HOMA-IR） was calculated. Embryo implantation， miscarriage rate， and average number of live fetuses were observed. Uterine tissue pathology was examined by HE staining， and mRNA expression of Il-6， Tnf-α， leukemia inhibitory factor （Lif）， homeobox gene 10 （Hoxa10）， prolactin family 8 subfamily A member 2 （Prl8a2）， and insulin-like growth factor-binding protein 1 （Igfbp1） in the uterine tissue was detected by qRT-PCR. ResultsCompared with the normal group， the model group had significantly higher blood glucose level at 0， 30， 60， 90， and 120 minutes， increased miscarriage rate， elevated HOMA-IR， decreased average number of live fetuses， lower level of P₄ and E₂， higher level of IL-6， TNF-α， and FINS， and higher mRNA expression of Il-6 and Tnf-α in the uterine tissue. The mRNA expression of Lif， Hoxa10， and Prl8a2 was reduced （P＜0.05 or P＜0.01）. The uterus had a dark red color， visible areas of bleeding， fewer embryos with developmental abnormalities， and increased placental necrosis. Pathological examination revealed thrombus in the decidual layer， unclear decidual cell morphology， loose arrangement， scattered distribution， edema degeneration in the cytoplasm， and nuclear shrinkage or disappearance， with extensive infiltration of inflammatory cells. In contrast， compared with the model group， the MSP group showed significantly lower blood glucose level at 0， 30， 60， 90， and 120 min， reduced miscarriage rate， lower HOMA-IR， increased number of live fetuses， higher level of P₄ and E₂， and lower level of IL-6， TNF-α， and FINS. The mRNA expression of Il-6 and Tnf-α in the uterine tissue was lower， while the expression of Lif， Hoxa10， and Prl8a2 mRNA was higher （P＜0.05 or P＜0.01）. There was significant improvement in uterine and embryo conditions， as well as in uterine tissue pathology. ConclusionThe MSP can reduce the miscarriage rate in a PCOS model with hyperandrogenism， insulin resistance， and miscarriage. Its mechanism may involve inhibiting inflammation， improving endometrial receptivity， and restoring the defects in endometrial decidualization.

ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.

Objective To investigate the seroprevalence of antibody against Toxoplasma gondii among patients with hematological malignancies, and compare it with that among health individuals, so as to provide insights into unraveling the pathogenesis of hematological malignancies. Methods A total of 225 patients with hematological malignancies in Department of Hematology, Xuzhou Central Hospital and 300 healthy individuals in the same hospital were enrolled from 2017 to 2024. Blood samples were collected from all subjects, and the serum IgG and IgM antibodies against T. gondii were detected using chemiluminescent immunoassay. Demographic and clinical features were collected from patients with hematological malignancies, including gender, age, contact with cats, consumption of raw or undercooked meat, type of malignancy, clinical symptoms, blood transfusion and treatment, and the seroprevalence of anti-T. gondii antibody was compared among patients with different characteristics. Results The age (t = 0.72, P > 0.05) and gender (χ² = 0.93, P > 0.05) were compared between patients with hematological malignancies and healthy individuals. The seroprevalence of T. gondii infection was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), and the seroprevalence of anti-T. gondii IgG antibody was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), while there was no significant difference in the seroprevalence of anti-T. gondii IgM antibody between patients with hematological malignancies and healthy individuals (1.33% vs. 0; corrected χ² = 2.02, P > 0.05). The seroprevalence of T. gondii infection was 23.08% among patients with leukemia, 16.67% among patients with lymphoma, 19.23% among patients with multiple myeloma, 24.00% among patients with myeloproliferative neoplasm, and 26.09% among patients with myelodysplastic syndrome (χ² = 1.44, P > 0.05), and was all higher than among healthy individuals (corrected χ² = 23.92, 10.74, 13.76, 12.84 and 14.54; all P values < 0.01). In addition, there were no significant differences in the detection of anti-T. gondii antibody among patients with hematological malignancies in terms of gender, age, contact with cats, consumption of raw or undercooked meat, chemotherapy or blood transfusion (χ² = 0.76, 1.97, 0, 2.81, 2.38 and 0.66; all P values > 0.05). Conclusions There is a high risk of T. gondii infection among patients with hematological malignancies, and intensified surveillance of T. gondii infection is recommended among patients with hematological malignancies.

BACKGROUND:Ca2+expression in astrocytes has been found to be closely related to cognitive function,and the Ca2+signaling pathway regulated by inositol 1,4,5-trisphosphate receptors(IP3R2)and ryanodine receptor(RYR)2 receptors has become a hot spot in the study of cognitive disorder-related diseases. OBJECTIVE:To investigate the expression of Ca2+signals mediated by IP3R2 and RYR2 in hippocampal astrocytes in animal models of delayed encephalopathy after acute carbon monoxide poisoning,and to explore the possible pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning. METHODS:C57BL mice with qualified cognitive function were selected by Morris water maze experiment and randomly divided into control group and experimental group.An animal model of delayed encephalopathy after acute carbon monoxide poisoning was established by static carbon monoxide inhalation in the experimental group,and the same amount of air was inhaled in the control group.Behavioral and neuronal changes,astrocyte specific marker glial fibrillary acidic protein,IP3R2,RYR2 receptor and Ca2+concentration in astrocytes of the two groups were detected using Morris water maze,hematoxylin-eosin staining,western blot,immunofluorescence double labeling and Ca2+fluorescence probe at 21 days after modeling. RESULTS AND CONCLUSION:In the Morris water maze,the escape latency of the experimental group was significantly longer than that of the control group(P<0.05).Hematoxylin-eosin staining results showed that in the experimental group,the number of hippocampal pyramidal cells decreased,the cell structure was disordered,and the nucleus was broken and dissolved.Immunofluorescence results showed that IP3R2 and RYR2 were co-expressed with glial fibrillary acidic protein in the hippocampus,and the expressions of IP3R2,RYR2 and glial fibrillary acidic protein were up-regulated in the hippocampus of the experimental group(P<0.05).Western blot analysis showed that the expressions of IP3R2,RYR2,and glial fibrillary acidic protein in the hippocampus of the experimental group were increased(P<0.05).Ca2+concentration in hippocampal astrocytes increased significantly in the experimental group(P<0.05).To conclude,astrocytes may affect Ca2+signals by mediating IP3R2 and RYR2 receptors,then impair the cognitive function of mice with carbon monoxide poisoning,and eventually lead to delayed encephalopathy after acute carbon monoxide poisoning.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

OBJECTIVE: To analyze the origin and influencing factors the titer of ABO blood group antibody in neonates. METHODS: A total of 303 newborn blood samples collected in our hospital from August 2023 to March 2024 were selected for the detection of ABO blood group settings and the determination of the total titers of IgG and IgM blood group antibodies in plasma. IgM antibodies were treated with dithithreitol (DTT) to determine the titers of IgG antibodies. The total titer of the blood group antibody was compared with that of the IgG antibody. The clinical data of mothers and newborns were collected, and the correlation between the antibody titer and these clinical data was analyzed. RESULTS: Among the 303 newborn specimens, 14 cases (4.62%) were identified to possess blood group antibodies. The influence of the maternal ABO blood group on the generation of high-potency blood group antibodies in newborns was observed to follow the order of O>B>A>AB, with a significant statistical difference ( P < 0.01). Of the 123 (40.59%) newborns born to mothers of type O, 121 (98.37%) had blood group antibody titers > 2. Of the 20 (6.60%) newborns born to mothers of type AB, all 20 (100.00%) had blood group antibody titers < 2. Among 89 (29.37%) mothers of type A and 71 (23.43%) mothers of type B, the titer of 100% newborn blood group antibody was less than 2, when the newborn blood group was incompatible with the mother's blood group; the titer of the newborn blood type antibody was higher or lower, when the newborn blood type was compatible with the mother's blood type. The titer of the newborn blood group antibodies is related to the number of pregnancies of the mothers and has no association with other clinical data (such as the mother's number of obortions), the number of production, fetal gestation age. CONCLUSION The majority of ABO blood group antibodies in neonates are IgG antibodies from the mothers, and few are produced by the neonates themselves. In some neonates, IgG anti-A and/or anti-B can agglutinate with anti-stereotyped cells at room temperature. The maternal ABO blood type is the primary factor influencing the titer of the newborn blood type. The number of maternal pregnancies is a factor affecting the high titer ABO blood group antibodies in newborns.
Humans ; Infant, Newborn ; ABO Blood-Group System/immunology* ; Female ; Immunoglobulin G/blood* ; Immunoglobulin M/blood* ; Pregnancy ; Blood Grouping and Crossmatching

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.
Humans ; Male ; Female ; Adult ; Visual Perception/physiology* ; Electric Stimulation ; Middle Aged ; Young Adult ; Electrocorticography ; Electroencephalography ; Brain Mapping

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis