Polycystic ovary syndrome （PCOS） is one of the most prevalent gynecological diseases， and its incidence is increasing year by year， seriously affecting the physical and mental health of female patients. The pathogenesis of this disease is complex and has not been fully clarified. At present， PCOS is mainly treated by Western medicine， which， however， has poor efficacy and induces various adverse reactions. Therefore， developing safe and effective therapies has become a difficult problem that needs to be solved. Studies have confirmed that traditional Chinese medicine （TCM） can regulate phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， Toll-like receptor 4/nuclear factor-κB （TLR4/NF-κB）， transforming growth factor-β （TGF-β）/Smads， secreted glycoprotein/β-catenin （Wnt/β-catenin）， adenosine monophosphate-activated protein kinase （AMPK）， and advanced glycation endproduct/receptor for advanced glycation endproducts （AGE/RAGE） signaling pathways to ameliorate insulin resistance， inhibit inflammation and oxidative stress， regulate endocrine hormone disorders， and intervene in apoptosis and autophagy， thus alleviating the symptoms， slowing down the disease progression， and improving the ovarian function. The treatment of PCOS with TCM has demonstrated definite effects and high safety. Therefore， exploring this disease from cellular and molecular perspectives can provide a theoretical basis for its clinical treatment and new drug development. However， there is a lack of systematic reviews on the modulation of relevant signaling pathways by TCM in the treatment of PCOS. This article reviews the research progress in the treatment of PCOS with the active ingredients and compound prescriptions of TCM by regulating relevant signaling pathways in recent years， with the aim of providing evidence to support the promotion of TCM for treating PCOS in the future.

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 analyze the prevalence of potentially inappropriate medication （PIM） in elderly patients with femoral neck fractures at admission and compare the concordance of 3 evaluation criteria. METHODS A retrospective study was conducted to review the data of elderly patients with femoral neck fractures admitted to the Department of Orthopedics in Northern Jiangsu People’s Hospital from July 2022 to June 2023. The PIMs were identified according to the Criteria of Potentially Inappropriate Medications for Older Adults in China：2017 edition （hereinafter referred to as Chinese criteria）， American Geriatrics Society 2023 Updated AGS Beers Criteria® for Potentially Inappropriate Medication in Older Adults （hereinafter referred to as 2023 Beers criteria）， third version criteria for screening tool of older people’s prescriptions for potentially inappropriate medication （hereinafter referred to as STOPP criteria version 3）. The concordance of the 3 evaluation criteria was compared by using Kappa statistics. RESULTS A total of 246 patients were included in this study； 49 patients （19.92%） with 77 PIMs were detected by the Chinese criteria， 64 patients （26.02%） with 118 PIMs were detected by the 2023 Beers criteria， and 41 patients （16.67%） with 67 PIMs were detected by the STOPP criteria version 3； 22 patients met all three criteria simultaneously. The concordance among the three criteria showed moderate agreement （0.417≤Kappa≤0.486） when compared in pairs. CONCLUSIONS There are certain differences in the PIM evaluated by the three criteria， but the prevalence of PIMs is below 30% according to the different H202134） criteria. Benzodiazepines， antipsychotics， antidepressants， and other drugs may increase the risk of patients falling again.

AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.

Objective To explore the effect of open reading frame 66(C12ORF66)located at chromosome 12 on the viability of MYCN amplified NB cell lines.Methods DDatasets GSE16476 and GSE49710 in R2 database were analyzed for expression level of C12ORF66 in MYCN amplified and MYCN non-amplified NB cells and its potential correlation with the prognosis of pediatric patients.C12ORF66 mRNA expression level in normal tissue immortalized cell lines,MYCN amplified and MYCN non-amplified cell lines were detected by RT-qRCR.Transient or stable knockdown of C12ORF66 cell lines were constructed to compare the difference in real time cellular analysis(RTCA),colony formation,Ki67 positive cells between the control group and the C12ORF66 knockdown group.Results By analyzing R2 datasets,C12ORF66 level in MYCN amplified samples was significantly higher than that in MYCN non-amplified samples,and the expression of C12ORF66 was negatively correlated with the prognosis of pediatric patients(P＜0.05).C12ORF66 highly expressed in MYCN-amplified BE(2)-C and SK-N-BE(2)cell lines than in MYCN non-amplified CHLA-255 and SH-SY5Y cell lines(P＜0.001).Transient or stable knockdown of C12ORF66 resulted in significant slow down of proliferation of MYCN amplified NB cells(P＜0.001),the colony formation ability was significantly reduced(P＜0.001),and the proportion of Ki67 positive cells was significantly decreased(P＜0.05).Conclusions C12ORF66 was highly expressed in MYCN amplified clinical NB samples and cell lines which is believed to be correlated with poor prognosis of pediatric patients.C12ORF66 knockdown signifi-cantly inhibits cell viability of NB cells.

Objective To investigate the effect and mechanism of transplantation of neuregulin1(NRG1)gene-modified bone marrow mesenchymal stem cells(BMSCs)on the repair of hemi-transected spinal cord injury(SCI)in rats.Methods Isolated and cultured rat BMSCs,followed by transfection with the NRG1 gene.The levels of NRG1 in BMSCs lysate and culture supernatant was deected by ELISA method,and the proliferation activity of the BMSCs was detected by cell counting method.Forty-three healthy 8-week-old SD rats were randomly divided into control group(n=10),SCI model group(n=10),BMSCs group(n=10),and NRG1-BMSCs group(n=13).After establishing the spinal cord hemisection model,animals received in-situ transplantation of BMSCs or NRG1-BMSCs.On the 1,7,14,21,and 28 days after transplantation,the hind limb motor function was evaluated using BBB score and inclined plate test;on the 7th day after transplantation,the migration and distribution of transplanted cells was monitored using a fluorescence microscope;on the 28th day after transplantation,the pathological changes of rat spinal cord tissues was examined using HE staining and Nissl staining;cell apoptosis using TUNEL staining,and levels of endoplasmic reticulum stress-related proteins[X-box binding protein 1(XBP1),C/EBP homologous protein(CHOP),activating transcription factor 4(ATF4),ATF6,glucose-regulated protein 78(GRP78)]and apoptosis-related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated protein X(Bax)]in rat spinal cord tissues using Western blotting.Results BMSCs were successfully isolated,cultured,and transfected with the NRG1 gene.ELISA method results showed that the NRG1 contents in the NRG1-BMSCs lysate and culture supernatant were significantly higher than that of BMSCs in a time-dependent manner(P<0.05).The proliferation activity of NRG1-BMSCs was significantly higher than that of BMSCs(P<0.05).On the 21 and 28 days after transplantation,the BBB score and the slope angle of the inclined plate in NRG1-BMSCs group were higher than those in SCI model group or BMSCs group(P<0.05).However,it did not reverse to the level in control group(P<0.05).On the 28th day after transplantation,compared with the SCI model group and BMSCs group,neuronal pyknosis reduced,the Nissl body density increased,the expression levels of XBP1,CHOP,ATF4,ATF6,GRP78,and Bax,and the rate of TUNEL-positive cells significantly reduced in NRG1-BMSCs group(P<0.05),and the expression level of Bcl-2 significantly increased(P<0.05).Conclusion Transplantation of NRG1 gene-modified BMSCs can alleviate SCI and improve the recovery of motor function in rats.The mechanism may be related to promoting the proliferation activity of BMSCs,inhibiting cell apoptosis,and mitigating endoplasmic reticulum stress.

BACKGROUND:Heterotopic ossification of skeletal muscle is a clinically serious complication.For heterotopic ossification of skeletal muscles,the cells involved in the process of heterotopic ossification remain unclear. OBJECTIVE:To investigate the involvement of myocytes,fascia cells,and endothelial cells in the process of heterotopic ossification in skeletal muscle and to observe the cell origin of heterotopic ossification in skeletal muscle induced by bone morphogenetic protein 4. METHODS:Both C2C12 cells and the myotubes formed by the C2C12 cells in the induction medium were cultured,and 500 ng/mL bone morphogenetic protein 4 was added to the medium respectively,and whether the C2C12 cells and myotubes continued to proliferate within 10 days under the treatment were observed under a microscope.Myogenic cells(L6,derived from rats)and fibroblast-derived cells(derived from human)were co-cultured.After treatment with 500 ng/mL bone morphogenetic protein 4 and 10 ng/mL transforming growth factor-β,osteogenic and chondrogenic differentiation potential within 21 days were observed using Safranine O staining and Alcian blue staining.Using transgenic animal FVB/N-TgN(TIE2-LacZ)182Sato mice,15 μL of adeno-associated virus-bone morphogenetic protein 4(5×1010 PFU/mL)were implanted in the thigh muscle space of genetic mice for 10 and 14 days.X-gal staining was used to observe the formation of new blood vessel endothelium in the differentiated bone. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein 4 caused myotube breakdown and increased C2C12 cell proliferation.Compared with other groups,the pure fibroblast-derived cell group had a higher area of positive alcian blue and safarin O staining(P<0.05)and a lower area of alkaline phosphatase staining(P<0.05),while the pure L6 group had a bigger area of alkaline phosphatase staining(P<0.05)but a smaller area of positive alcian blue and safarin O staining(P<0.05).(2)Transplantation of adeno-associated virus-bone morphogenetic protein 4-adsorbed gelatin sponge into FVB/N-TgN(TIE2-LacZ)182Sato mice resulted in heterotopic ossification.(3)X-gal staining results demonstrated that there was no obvious staining in chondrocytes and differentiated bones and Tie2+ endothelial cells did not participate in the formation of the alienated bone.(4)These findings verify that fibroblasts are the primary source of osteoblasts during the adeno-associated virus-bone morphogenetic protein 4-induced ectopic endochondral ossification in skeletal muscle,but myogenic cells are the main source of osteoblasts.Tie2+ endothelial cells might not be the cell source for cartilage and bone.

Objective To analyze three-dimensional imaging characteristics and advantages for severe portal vein stenosis after liver transplantation, and to evaluate clinical efficacy of portal vein stent implantation. Methods Clinical data of 10 patients who received portal vein stent implantation for severe portal vein stenosis after liver transplantation were retrospectively analyzed. Imaging characteristics of severe portal vein stenosis, and advantages of three-dimensional reconstruction imaging and interventional treatment efficacy for severe portal vein stenosis were analyzed. Results Among 10 patients, 3 cases were diagnosed with centripetal stenosis, tortuosity angulation-induced stenosis in 2 cases, compression-induced stenosis in 2 cases, long-segment stenosis and/or vascular occlusion in 3 cases. Three-dimensional reconstruction images possessed advantages in accurate identification of stenosis, identification of stenosis types and measurement of stenosis length. All patients were successfully implanted with portal vein stents. After stent implantation, the diameter of the minimum diameter of portal vein was increased [(6.2±0.9) mm vs. (2.6±1.7) mm, P<0.05], the flow velocity at anastomotic site was decreased [(57±19) cm/s vs. (128±27) cm/s, P<0.05], and the flow velocity at the portal vein adjacent to the liver was increased [(41±6) cm/s vs. (18±6) cm/s, P<0.05]. One patient suffered from intrahepatic hematoma caused by interventional puncture, which was mitigated after conservative observation and treatment. The remaining patients did not experience relevant complications. Conclusions Three-dimensional visualization technique may visually display the location, characteristics and severity of stenosis, which is beneficial for clinicians to make treatment decisions and assist interventional procedures. Timely implantation of portal vein stent may effectively reverse pathological process and improve portal vein blood flow.

Hepatocellular carcinoma （HCC） is a common tumor in the digestive tract， the formation mechanism of which remains to be fully elucidated. Although surgery， radiation， chemotherapy， targeted therapy， and immunotherapy have achieved significant results in the treatment of HCC， these methods are accompanied by a considerable number of adverse reactions and complications. In recent years， Chinese medicine has shown remarkable efficacy in the treatment of HCC， and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine， which exerts therapeutic effects via multiple components and multiple targets. However， the pathogenesis of HCC is exceptionally complex and not fully understood， which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Hedgehog， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and transforming growth factor-β （TGF-β）/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis， inhibiting cell proliferation and migration， and blocking the cell cycle via the above pathways. However， the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets， new perspectives， and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.

Objective:To investigate the predictive value of early thyroid function changes on the efficacy of patients with Graves′ disease (GD) after 131I therapy. Methods:Data of patients with GD (59 males, 214 females; age (37.4±11.4) years) who underwent single therapy of 131I in Tianjin Medical University General Hospital from November 2017 to January 2019 were retrospectively analyzed. Symptoms, signs and laboratory tests (serum free triiodothyronine (FT 3) and serum free thyroxine (FT 4)) of patients were observed to assess the efficacy of 131I treatment. Efficacy was divided into complete remission (CR), partial remission (PR), non-remission (NR) or relapse. The changes of thyroid function (ΔFT 3=FT 3 before treatment-FT 3 after treatment)/FT 3 before treatment×100%; ΔFT 4=FT 4 before treatment-FT 4 after treatment)/FT 4 before treatment×100%) 1 month after 131I therapy in each efficacy group and differences among them were compared by using independent-sample t test, χ2 test, one-way analysis of variance and the least significant difference t test. ROC curves were drawn to analyze the predictive values of early thyroid function changes on the efficacy of 131I treatment for GD. Logistic regression analyses were performed to identify the influencing factors for the efficacy of 131I therapy. Results:CR rate and total effective rate of 273 GD patients after single therapy of 131I were 67.03%(183/273) and 92.67%(253/273), respectively. After 1 month, CR rate of euthyroidism group ( n=95) was significantly higher than that of hyperthyroidism group ( n=178; 81.05%(77/95) vs 59.55%(106/178); χ2=4.60, P=0.032). ΔFT 3 and ΔFT 4 at the first month were statistically significant and decreased sequentially in the CR group ( n=183), PR group ( n=70), NR or relapse groups ( n=20; F values: 15.40, 12.54, both P<0.001). ROC curve analysis showed that patients with ΔFT 3≥73.64% and (or) ΔFT 4≥59.03% had a higher probability of achieving CR, with sensitivities of 84.3% and 86.7%, and specificities of 62.6% and 62.6%, respectively. Logistic regression analysis showed that 24 h radioactive iodine uptake (odds ratio ( OR)=1.095, 95% CI: 1.031-1.139), dose of 131I given per gram of thyroid tissue ( OR=1.562, 95% CI: 1.321-1.694), ΔFT 3 ( OR=1.354, 95% CI: 1.295-1.482), ΔFT 4 ( OR=1.498, 95% CI: 1.384-1.608) were factors affecting the outcome of patients with GD treated with 131I treatment (all P<0.05). Conclusion:Effects of 131I treatment can be predicted based on the change of the thyroid function at the first month after 131I treatment in patients with GD.