OBJECTIVE: To investigate the risk factors associated with the development of knee osteoarthritis (OA) following arthroscopic surgery for degenerative lesions of the posterior horn of the medial meniscus. METHODS: Between January 2012 and January 2014, a retrospective analysis was conducted on 506 patients who underwent arthroscopic surgery for degenerative disease of the posterior horn of the medial meniscus. The cohort included 230 males and 276 females, aged from 32 to 58 years old with an average of (46.77±9.02) years old. According to the results of postoperative follow-up, patients were categorized into a knee osteoarthritis(OA) group and a non-OA group. The following parameters were recorded for each subject:gender, medial proximal tibial angle (MPTA), hip-knee-ankle angle (HKA), presence of bone edema on MRI, physical characteristics (including McMurray test results, locking symptoms, and medial knee tenderness points), meniscus protrusion, type of meniscus injury, and free body condition as observed via arthroscopy. Multivariate unconditional Logistic regression analysis was employed to investigate the associated factors influencing the 10-year postoperative incidence of knee osteoarthritis following surgery for degenerative injury of the posterior horn of the medial meniscus. Independent risk factors potentially influencing the development of postoperative OA were identified, and a nomogram-based predictive model for postoperative OA was established. The discriminatory ability and calibration accuracy of the model were assessed using the C-index and Hosmer-Lemeshow goodness-of-fit test, respectively. Furthermore, internal validation was performed using the bootstrap resampling method. RESULTS: Within a 10-year period following arthroscopic surgery, there were 123 patients in the OA group and 383 patients in the non-OA group. Significant differences were observed between two groups with respect to gender (χ²=5.156, P=0.023), MPTA<86.6° (χ²=21.671, P<0.001), varus lower limb alignment( χ²= 80.086, P<0.001). Additionally, meniscus extrusion (χ²=6.371, P=0.012), meniscus transverse tear (χ²=14.573, P<0.001), and bone edema detected on MRI(χ²=9.881, P=0.002) were identified as factors associated with the development of postoperative knee OA. The multifactorial Logistic regression analysis revealed that the lower limb line of force inversion OR=4.324, 95%CI (1.391, 13.443), P=0.011;MPTA <86.6°, OR=2.519, 95%CI (1.150, 5.519), P=0.021;transverse meniscus tear, OR=4.546, 95%CI (1.827, 11.310), P=0.001;meniscus ectropion, OR=5.401, 95%CI (1.992, 14.646), P=0.001;and bone edema manifestation on MRI OR=2.692, 95%CI (1.169, 6.200), P=0.020. They were independent risk factors associated with the development of postoperative OA. The area under the ROC curve predicted by the model was 0.927, 95%CI (0.903, 0.950). The Hosmer-Lemeshow goodness-of-fit test, used to evaluate the accuracy of the model, yielded P=0.689. Additionally, the internally sampled calibration curve demonstrated good consistency with the actual postoperative OA outcomes. CONCLUSION Varus alignment of the lower extremity, MPTA <86.6°, transverse meniscus tear, lateral meniscus injury, and bone marrow edema observed on MRI were independent risk factors for the development of knee osteoarthritis following arthroscopic surgery. Additionally, the prognostic model demonstrated excellent predictive performance.
Humans ; Male ; Female ; Middle Aged ; Arthroscopy/adverse effects* ; Adult ; Retrospective Studies ; Tibial Meniscus Injuries/surgery* ; Osteoarthritis, Knee/epidemiology* ; Risk Factors ; Menisci, Tibial/surgery* ; Incidence ; Postoperative Complications/epidemiology*

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Objective To explore the clinical efficacy and safety of Beimu Zhizhu Prescription(derived from the modification of Zhizhu Pills)in the treatment of GERC by retrospectively analyzing the clinical data of 297 patients with gastroesophageal reflux cough(GERC).Methods A retrospective cohort study was conducted in a total of 297 patients with GERC of rebellious stomach qi type who were admitted to the Outpatient Department of Wangjing Hospital of China Academy of Chinese Medical Sciences from July 2021 to July 2023.The patients were divided into an exposure group(136 cases)and a non-exposure group(161 cases)according to the medication of Beimu Zhizhu Prescription or not.The exposure group was treated with Beimu Zhizhu Decoction,and the non-exposure group was treated with proton pump inhibitor of Esomeprazole Magnesium Enteric-coated Tablets.A total of 119 pairs of cases were obtained after propensity score matching(PSM)at the ratio of 1 to 1.The changes of salivary pepsin level before and after treatment in the two groups were observed.After two weeks and eight weeks of treatment,the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching and gastric distension were compared between the two groups,and the incidence of adverse reactions was recorded.Results(1)After two weeks of treatment,the comparison of symptom remission rate after PSM showed that the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching and gastric distension in the exposure group were 84.87％(101/119),80.77％(84/104),82.61％(76/92),82.5％(66/80),84.42％(65/77),respectively,and those in the non-exposure group were 73.95％(88/119),72.90％(78/107),70.41％(69/98),65.38％(51/78),64.38％(47/73),respectively.The intergroup comparison showed that the remission rates for all of the symptoms except for acid reflux in the exposure group was significantly superior to that in the non-exposure group(P＜0.05 or P＜0.01).After eight weeks of treatment,the cough response rate and the remission rates for reflux-related symptoms of acid reflux,heartburn,belching,and gastric distension in the exposure group were 94.74％(36/38),91.67％(33/36),91.43％(32/35),93.75％(30/32),94.12％(32/34),respectively,and those in the non-exposure group were 77.78％(35/45),74.42％(32/43),71.43％(30/42),68.42％(26/38),66.67％(24/36),respectively.The intergroup comparison showed that the remission rate of all of the symptoms in the exposure group was significantly superior to that in the non-exposure group(P＜0.05 or P＜0.01).(2)After two weeks of treatment,the comparison of salivary pepsin level after PSM showed that the salivary pepsin level of the exposure group was significantly lower than that before treatment(P＜0.01),while that of the non-exposure group was not significantly decreased(P＞0.05).The decrease of salivary pepsin level in the exposure group was significantly superior to that in the non-exposure group.Statistically significant differences were presented in the post-treatment salivary pepsin level after two weeks of treatment and in the pre-and post-treatment difference of salivary pepsin level between the two groups(P＜0.05 or P＜0.01).(3)There were four cases(2.48％)of adverse reactions in the non-exposure group,while no related adverse reactions occurred in the exposure group.There was no significant difference in the incidence of adverse reactions between the two groups(x2=1.180,P=0.178).Conclusion Beimu Zhizhu Decoction can effectively relieve cough and reflux-related symptoms of acid reflux,heartburn,belching,and gastric distension in patients with GERC of rebellious stomach qi type,reduce the level of salivary pepsin,and has high safety.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Objective:To explore the influence of different depths of anesthesia under guidance of anesthesia depth detector on the awakening quality of elderly patients with colon cancer after laparoscopic surgery.Methods:A total of 96 elderly patients with colon cancer who underwent surgical resection and admitted to Beijing Changping District Hospital from February 2017 to June 2020 were selected.They were randomly divided into mild anesthesia group,moderate anesthesia group and deep anesthesia group according to the random sampling,with 32 in each group.The bispectral index(BIS)of deep anesthesia group was within 30-39 interval,and the BIS of moderate anesthesia group was within 40-49 interval,and the BIS of mild anesthesia group was within 50-60 interval.The Prince-Henry pain scale scores of patients with different depths of anesthesia under anesthesia depth detector were observed.The stress response-related indicators included adrenocorticotropic hormone(ACTH),cortisol(Cor)and interleukin-6(IL-6)of patients at three different time points:pre operation(S1),intra operation(S2)and post operation(S3)were monitored.Additionally,the differences of the incidences of complications and the cognitive function also were analyzed.Results:The postoperative Prince-Henry pain scores of the three groups of patients with colon cancer showed there were no statistically significant differences among anesthesia groups with different depths(P>0.05).The stress response indicators included ACTH,Cor and IL-6 appeared significant time-dependent changes among anesthesia groups with different depths.The stress response indicators of all groups significantly increased at S2 point,and the ACTH,Cor and IL-6 levels of mild anesthesia group were respectively(13.73±1.63)nmol/L,(269.24±31.46)nmol/L and(83.67±3.44)μg/L,and these of moderate anesthesia group were respectively(18.26±2.52)nmol/L,(242.56±36.75)nmol/L and(109.35±6.44)μg/L,and these of deep anesthesia group were respectively(19.42±2.42)nmol/L,(432.35±31.34)nmol/L and(132.42±2.31)μg/L.There were significant differences in these indicators in same group between S2 point and S1 point(tmild group=7.99,12.48,16.48,tmoderate group=2.19,6.82,3.03,tdeep group=14.21,5.11,20.14,P＜0.05),respectively.The differences of the incidence rates of complication between the mild anesthesia group and the moderate anesthesia group,and between the mild anesthesia and the deep anesthesia group were statistically significant(x2=6.342,5.238,P<0.05),respectively.The MMSE scores 24 hours after surgery indicated that the difference of that between mild anesthesia group and deep anesthesia group,and between moderate anesthesia group and deep anesthesia group were significant(t=4.74,3.77,P<0.05),respectively.Conclusion:The depth of anesthesia has a significant influence on postoperative recovery quality,stress response and cognitive function.Using anesthesia depth detector to adjust the different depth of anesthesia can help to improve the awakening quality of elderly patients with colon cancer post-surgery and reduce the incidence of adverse reactions.

Objective To investigate the mechanism of micellar curcumol (MC) regulating the immune microenvi-ronment of ovarian cancer by promoting the polarization of M2-type macrophages to M1-type in ovarian cancer asci-tes.Methods ① After the mice were divided into groups, a mouse ovarian cancer ascites model was constructed by using the mouse ovarian cancer cell line ID8.Then weight changes were observed, tumor tissue and ascites were collected.The expression of CD86 and CD206 on macrophages of the tumor tissue and ascites was detected by flow cytometry.The expression of protein kinase B (PKB/Akt)/mammalian target of rapamycin (mTOR) was detected by Western blot.②A human monocytic leukemia cell line (THP-1) was induced to transform into M2 macrophage (THP-1 M2 macrophage) in vitro, and then treated with 10μg/ml MC.The apoptosis was detected by flow cytom-etry.The mRNA levels of macrophage mannose receptor (CD206), transforming growth factor-β(TGF-β), inter-leukin (IL)-1β and tumor necrosis factor-α (TNF-α) were detected by qRT-PCR.The expression of CD86 and CD206 was detected by flow cytometry, and Akt/mTOR expression and phosphorylation was detected by Western blot.Results ① In vitro study showed that the average body weight of the MC group was lower than that of the control group.Compared with the control group, CD206 expression of macrophages decreased in tumor tissue and ascites in the MC group, while the expression of CD86 increased.The Akt and mTOR phosphorylation level of mac-rophages in the MC group's ascites was lower than that in control group.②In vivo study showed that there was no difference in apoptosis rate among the groups detected by flow cytometry.The mRNA expression level of CD206, TGF-β and the protein expression level of CD206 in MC group were significantly lower than those in the control group, while the mRNA expression of IL-1β, TNF-α and the protein expression level of CD86 were significantly higher than those in the control group.Compared with the control group, the phosphorylation level of Akt and mTOR in the MC group decreased.Conclusion MC promotes M1 polarization of macrophages in ascites to regulate the immune microenvironment of ovarian cancer, which may be related to the Akt/mTOR pathway.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Based on the traditional Chinese medicine （TCM）'s understanding of consumptive thirst disease and modern medicine's understanding of the etiology of diabetes mellitus and the evolution of the disease， this article discussed the rationality and clinical significance of using "sugar collateral disease" as the name of diabetes mellitus in TCM， to provide a reference for modernization and development of TCM diseases' names. It is argued that the clinical manifestations described in the TCM disease name of consumptive thirst disease are only at a certain stage of diabetes mellitus， and it is difficult to cover the clinical characteristics of modern diabetes mellitus comprehensively. In 2003， academician TONG Xiaolin proposed to use "sugar collateral disease" as the TCM disease name of diabetes mellitus， which on the one hand can reflect the essence of diabetes mellitus， and on the other hand can embody the disease location， disease mechanism and the evolution of the disease， highlight the harms of complications， and serve as a warning for the early diagnosis and treatment of the disease， which can help to enhance the level of diagnosis and treatment of diabetes mellitus in TCM.