ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss （RPL） by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus （Shoutai Wan， Juyuan Jian）-of traditional Chinese medicine （TCM） at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c （blank group） and DBA/2 （modeling group） mice separately. Pregnant mice in the modeling group were randomly grouped as follows： high/low-dose Shoutai Wan， high/low-dose Juyuan Jian， model （RPL）， and positive control （dydrogesterone）， with 10 mice in each group. Starting from the day after the detection of the vaginal plug， mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention， the following indicators were measured. ① Macroscopic evaluation： general conditions， uterine wet weight， embryo loss rate， four coagulation parameters ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， fibrinogen （FIB）， and thrombin time （TT）］， and peripheral blood estradiol （E₂） and progesterone （Pg） levels. The decidua with embryos was stained with hematoxylin-eosin （HE） and evaluated by transmission electron microscopy （TEM）. The expression of B-cell lymphoma-2 （Bcl-2）， vascular endothelial growth factor （VEGF）， angiotensin Ⅱ （AngⅡ）， matrix metalloproteinase-2 （MMP-2）， interleukin-6 （IL-6）， leukemia inhibitory factor （LIF）， CXC chemokine ligand 12 （CXCL12）， and microtubule-associated protein 1 light chain 3 homolog （LC3）Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level： The decidua with embryos from the blank， model， high-dose Shoutai Wan， and high-dose Juyuan Jian groups （6 mice per group， with 3 single-cell samples per group， totaling 24 mice） were analyzed by the BD Rhapsody™ platform， and the whole-cell atlas was drawn by uniform manifold approximation and projection （UMAP） dimensionality reduction clustering combined with the single-cell mouse cell atlas （scMCA）. The differentially expressed genes （DEGs） and cell interaction networks were analyzed via Gene Ontology （GO）， Kyoto Encyclopedia of Genes and Genomes （KEGG）， and CellChat， and the protein-protein interaction （PPI） map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells （natural killer cells， NK cells） from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group， the RPL group showed an increase in the embryo loss rate （P<0.01）， down-regulated expression of Bcl-2， LIF， MMP-2， and Vegf in the decidua with embryos （P<0.05）， up-regulated protein levels of CXCL-12， AngⅡ， and IL-6 （P<0.05）， blocked angiogenesis， apoptosis-inflammation imbalance， and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance， and Shoutai pill showed superior performance in restoring the E₂ level to the Pg level （P<0.05）. ② Single-cell transcriptome analysis indicated that compared with the blank group， the RPL group showed differences in multiple key cell populations such as decidual cells， trophoblast cells， endothelial cells， erythroblasts， NK cells， and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group， high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer （upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes） and macrophages （upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes） through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins， cell adhesion， and programmed cell death， thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells （up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes） and macrophages （up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes）， which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D， CDH5， GDF， and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 （STAT3） and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis （TWEAK） signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7， a decreased proportion of reparative dNK4， and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1， thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method （Shoutai Wan） has an advantage in regulating the phenotypes of unfolded protein， cell adhesion， and programmed cell death， and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method （Juyuan Jian） has an advantage in regulating epithelial-mesenchymal transition （EMT）， angiogenesis， and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.

ObjectiveTo observe the clinical efficacy and safety of Guben Quyu Jiedu prescription in treating nocturnal hypoxemia of chronic obstructive pulmonary disease （COPD） combined with Obstructive sleep apnea hypopnea syndrome （ OSAHS ） （deficiency of lung， spleen and kidney with blood stasis and toxicity）. MethodsThe paper used a forward-looking， random double-blind， placebo-controlled design method to select 96 patients with COPD combined with OSAHS， and their traditional Chinese medicines （TCM） syndrome differentiation was deficiency of lung， spleen and kidney with blood stasis and toxicity. These patients were randomly divided into the observation group and the control group， with 48 cases in each group. Based on conventional Western medicine treatment， the observation group was treated with Guben Quyu Jiedu prescription and the control group was treated with traditional Chinese medicine placebo. Both courses of treatment were 90 days. Then the paper compared the changes in minimum pulse oxygen saturation （SpO₂） during the night， apnea index （AHI）， OSAHS efficacy evaluation， TCM syndrome efficacy evaluation， and TCM symptom score before and after treatment between the two groups. ResultsThere were 5 withdrawals in the observation group and 8 withdrawals in the control group， so 43 cases in the observation group and 40 cases in the control group completed the trial. Compared with the condition before treatment， the minimum SpO₂ during the night and AHI in the observation group were significantly improved at night （P<0.01） and were better than those in the control group （P<0.01）. OSAHS efficacy in the observation group was better than in the control group （χ²=7.085， P<0.05）. In terms of TCM syndrome efficacy， the total effective rate was 81.40% （35/43） in the observation group， significantly higher than that in the control group， which was 15.00% （6/40） （χ²=36.78， P<0.01）. The TCM symptom scores of the two groups were improved compared with the condition before treatment， and the effect of the two groups was similar in the four main symptoms of snoring， choking， lethargy， and cough. However， the observation group was better than the control group in 10 details such as dizziness， headache， chest tightness， chest pain， wheezing， dry mouth， and thirst （P<0.05）. ConclusionUsing Guben Quyu Jiedu prescription combined with conventional Western medicine can treat COPD combined with OSAHS hypoxemia at night （deficiency of lung， spleen and kidney with blood stasis and toxicity）. In this way， the minimum pulse oxygen saturation （SpO₂） of patients， the level of disease control， and the quality of life of patients can be improved， and the clinical symptoms can be relieved.

Background High-sensitivity C-reactive protein (hs-CRP) is a sensitive biomarker for cardiovascular disease (CVD) and can independently predict the risk of cardiovascular events. Although the association between per- and polyfluoroalkyl substances (PFAS) exposure and CVD risk has been widely reported, studies on the association between hs-CRP and PFAS remain limited. Objective To investigate the association between PFAS and hs-CRP levels, to provide a scientific basis for early identification and prevention of environment-related cardiovascular events. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) database (2015–2018). Based on predefined inclusion and exclusion criteria, a total of 3219 participants were included for subsequent analysis. Five PFAS with detection rates exceeding 90% were selected as exposure factors and log-transformed (lnPFAS) for subsequent analysis, including perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA). After selecting potential confounders through a change-in-estimate approach, logistic regression was employed to examine the effects of individual PFAS on serum hs-CRP level. Additionally, quantile g-computation and Bayesian kernel machine regression (BKMR) were applied to assess the combined effects of PFAS mixtures on hs-CRP. Results The study included 3219 participants with a mean age of (50.4±17.6) years, of whom 1554 (48.28%) were male. The median concentrations of the five PFAS compounds were: 1.20 ng·mL⁻¹ (PFHxS), 0.50 ng·mL⁻¹ (PFNA), 1.50 ng·mL⁻¹ (PFOA), 5.20 ng·mL⁻¹ (PFOS), and 0.20 ng·mL⁻¹ (PFDA). The Wilcoxon rank-sum tests revealed statistically significant differences between the elevated serum hs-CRP (≥2 mg·L⁻¹) and normal (<2 mg·L⁻¹) groups for all five PFAS compounds (PFHxS: P=0.005; PFNA: P=0.009; PFOA: P<0.001; PFOS: P<0.001; PFDA: P<0.001). After adjusting for potential confounders, the analysis of individual PFAS exposure demonstrated significant negative associations between serum hs-CRP levels and both ln-PFOS (OR: 0.87; 95%CI: 0.79, 0.96; P=0.0036) and lnPFDA (OR: 0.78; 95%CI: 0.71, 0.86; P < 0.001). The joint effect analysis using quantile g-computation revealed an overall inverse association between PFAS mixtures and hs-CRP, with lnPFDA emerging as a primary contributor; an similar association was observed in males, but not significant in females. Further evaluation through BKMR showed that when PFAS mixture concentrations reached or exceeded P₇₀, their combined effect on hs-CRP became significantly lower than when all PFAS concentrations were at P₅₀, establishing a clear negative dose-response relationship. Conclusion The mixed exposure to PFAS showed a significant negative joint effect on serum hs-CRP levels, with PFDA being the key component contributing to this combined effect. Future prospective cohort studies are warranted to further validate these findings and elucidate the underlying mechanisms involved.

OBJECTIVE To analyze the influential factors for rivaroxaban-induced bleeding events in patients with non- valvular atrial fibrillation （NVAF） and coronary heart disease. METHODS A total of 64 hospitalized patients with NVAF complicated with coronary heart disease who were treated with rivaroxaban and admitted to the Fuzhou University Affiliated Provincial Hospital from November 2021 to May 2023 were included in this retrospective study. The demographic data， laboratory test indexes and other general clinical data， and steady-state trough concentration of rivaroxaban were collected， and the dose- adjusted trough concentration was calculated. The occurrence of bleeding events within 6 months after discharge was recorded. The univariate analysis and binary Logistic regression analysis were adopted to determine the independent risk factors of rivaroxaban- related bleeding events. The binary Logistic regression equation was constructed to predict the probability of bleeding events. The area under the receiver operator characteristic （ROC） curve （AUC） was used to analyze the predictive value of the regression equation. RESULTS Among 64 patients， 19 patients had 24 case-times bleeding events， most of which were mild bleeding （19 case-times， 79.2%）， and mainly gastrointestinal bleeding （17 case-times， 70.8%）. After symptomatic treatment and adjustment of the anticoagulant regimen， most of them were improved or cured. In the univariate analysis， the proportion of patients with a history of anemia， platelet count， urea nitrogen content， steady-state trough concentration of rivaroxaban， dose-adjusted trough concentration and coagulation indexes [international normalized ratio， prothrombin time （PT）， activated partial thromboplastin time] in bleeding group were significantly more or higher than those in non-bleeding group， while the albumin level was significantly lower than that in non-bleeding group （P＜0.05）. In binary Logistics regression analysis， high PT level （odds ratio＝1.473， 95% confidence interval＝1.103-1.967， P＝ 0.009） and high rivaroxaban dose-adjusted trough concentration （odds ratio＝1.174， 95% confidence interval＝1.018-1.355， P＝ 0.027） were independent risk factors for rivaroxaban-related bleeding events. The binary Logistic regression equation of bleeding event prediction probability （P） was LogitP＝－6.975+0.387×PT level+0.161×dose-adjusted trough concentration， and the AUC of the ROC curve was 0.825 （95% confidence interval was 0.708-0.909， P＜0.001）. CONCLUSIONS The risk factors of rivaroxaban-related bleeding events in patients with NVAF and coronary heart disease include previous anemia history， high platelet count， high urea nitrogen content， high rivaroxaban steady-state trough concentration， high dose-adjusted trough concentration， high coagulation indexes and low albumin level. High PT level and high dose-adjusted trough concentration are independent risk factors that can be used to predict the risk of rivaroxaban-induced bleeding events. The regression equation has good predictive value.

Objective:To analyze the clinical value of indocyanine green (ICC) fluorescence imaging in Mirizzi syndrome type Ⅱ-Ⅲ laparoscopic cholecystectomy (LC).Methods:A retrospective analysis was performed on 80 patients diagnosed with Mirizzi syndrome types Ⅱ-Ⅲ who underdoing LC in Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from October 2018 to February 2022, including 32 males and 48 females, aged (63.5±6.9) years. Patients were divided into two groups based on whether ICG fluorescence imaging technology was used, the control group ( n=38) that patients were treated with conventional LC and the experimental group ( n=42) patients were treated with LC guided by ICG fluorescence imaging. In the experimental group, the extrahepatic bile duct was identified by ICG fluorescence imaging during LC, and ICG was injected intraoperally to determine the reserved blood flow of gallbladder flap for fluorescence imaging and determine the resection line. Operation time, intraoperative blood loss, conversion rate of laparotomy and postoperative complications (bile leakage, incision infection, etc.) were compared between the two groups. Intraoperative fluorescence imaging and determination of the modified resection line of reserved gallbladder were analyzed in the observation group. Results:There was no significant difference in age, male proportion, type of Mirizzi syndrome and conversion rate of laparotomy between the two groups (all P>0.05). In the observation group, the operative time was (208.7±32.0) min, the intraoperative blood loss was (50.5±23.8) ml, and the biliary leakage was 7.1% (3/42), which was lower than that in the control group (228.2±33.9) min, (73.8±31.0) ml, 26.3% (10/38). The differences were statistically significant (all P<0.05). Of 37 cases (88%) showed common hepatic duct and common bile duct successfully in the observation group. In the observation group, ICG fluorescence imaging was used to determine the gallbladder resection line in 8 cases (19.0%). The gallbladder flap without fluorescence imaging was removed. Conclusion:ICG fluorescence imaging in LC for Mirizzi syndrome patients can identify the common bile duct and hepatic duct to guide surgical resection, determine the gallbladder flap resection line, reduce postoperative bile leakage and bleeding, and accelerate the surgical progress.

ObjectiveBioinformatics methods were used to systematically identify the Salvia miltiorrhiza terpenoid synthase （SmTPS） gene family members and predict their functions from the perspective of the genome. MethodThe genome and transcriptome data of S. miltiorrhiza， Arabidopsis thaliana， and tomato were obtained from the national genomics data center （NGDC）， national center for biotechnology information （NCBI）， the Arabidopsis information resource （TAIR）， and tomato functional genomics database （TFGD）， and the whole genome identification and bioinformatics analysis of the SmTPS gene family member were carried out with the help of Perl language programming， Tbtools， and other bioinformatics tools. ResultA total of 52 TPS gene family members were identified， and they were distributed on eight chromosomes of S. miltiorrhiza. Their coding amino acid number was 207-822 aa. The isoelectric points were 4.76-9.16. The molecular mass was 24.11-94.81 kDa， and all members are hydrophilic proteins. Gene structure analysis showed that there were significant differences in the number of introns among different subfamilies. The number of introns in 72.6% of TPS-a， b， and g subfamilies was 6， and that in 88.9% of TPS-c and e/f subfamilies was more than 10. Protein motifs were conserved among TPS subfamilies. The analysis of promoter cis-acting elements showed that all promoters of the SmTPSs contained a large number of light-responsive elements， and most of them had hormone-responsive elements. Gene expression analysis showed that SmTPS gene family members exhibited tissue-specific expression， and 24 of them responded to exogenous methyl jasmonate. ConclusionBased on the published S. miltiorrhiza genome， 52 SmTPS gene family members were identified， and their functions were predicted based on the phylogenetic analysis and expression patterns. This paper provides reference information for the further biosynthesis pathway and regulatory mechanism analysis of terpenoids in S. miltiorrhiza.

Objective:To analyze the epidemiological characteristics and economic burden of palmoplantar pustulosis (PPP) in China.Methods:A population-based retrospective study was conducted using the data from China′s Urban Basic Medical Insurance data from January 1, 2012, to December 31, 2016. International Classification of Diseases code and diagnoses in Chinese for PPP were used to identify cases and estimate the prevalence, incidence, and cost. Subgroup analyses were performed according to age and sex, and sensitivity analyses were conducted to evaluate the robustness of the results. Age-adjusted prevalence rates were calculated based on the 2010 national census data.Results:The crude prevalence and incidence rate of PPP in 2016 were 2.730/100 000 (95% CI: 2.218/100 000-3.242/100 000) and 1.556/100 000 (95% CI: 1.154/100 000-1.958/100 000), and the prevalence rate of females (2.910/100 000) was higher than that of males (2.490/100 000, χ2=97.48, P=0.001). The incidence rate of females (1.745/100 000) was also higher than that of males (1.418/100 000, χ2=85.02, P=0.001). The age peak of incidence and prevalence of patients with PPP was in the 30-39-year age group and a small peak existed in the 0-3-year age group among people under 20 years old. From 2012 to 2016, the average number of visits was (2.44±0.04) per patient, and the total per-capita cost per year was (982.40±39.19) yuan. Conclusion:In 2016, the prevalence and incidence rate of PPP in China were higher in females than in males, and the highest age peak was in the 30-39-year age group.

Objective:To analyze the epidemiological characteristics and economic burden of palmoplantar pustulosis (PPP) in China.Methods:A population-based retrospective study was conducted using the data from China′s Urban Basic Medical Insurance data from January 1, 2012, to December 31, 2016. International Classification of Diseases code and diagnoses in Chinese for PPP were used to identify cases and estimate the prevalence, incidence, and cost. Subgroup analyses were performed according to age and sex, and sensitivity analyses were conducted to evaluate the robustness of the results. Age-adjusted prevalence rates were calculated based on the 2010 national census data.Results:The crude prevalence and incidence rate of PPP in 2016 were 2.730/100 000 (95% CI: 2.218/100 000-3.242/100 000) and 1.556/100 000 (95% CI: 1.154/100 000-1.958/100 000), and the prevalence rate of females (2.910/100 000) was higher than that of males (2.490/100 000, χ2=97.48, P=0.001). The incidence rate of females (1.745/100 000) was also higher than that of males (1.418/100 000, χ2=85.02, P=0.001). The age peak of incidence and prevalence of patients with PPP was in the 30-39-year age group and a small peak existed in the 0-3-year age group among people under 20 years old. From 2012 to 2016, the average number of visits was (2.44±0.04) per patient, and the total per-capita cost per year was (982.40±39.19) yuan. Conclusion:In 2016, the prevalence and incidence rate of PPP in China were higher in females than in males, and the highest age peak was in the 30-39-year age group.

Objective:To investigate the etiological diagnostic value of metagenomic sequencing in central nervous system (CNS) infectious diseases.Methods:A total of 170 patients with central nervous system infection admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2020 were selected as the study subjects according to inclusion and exclusion criteria. General clinical data and pathogen test results were collected. All included patients underwent routine examination and mNGS test, and were divided into the conventional method test group and mNGS test group according to the test results. The measurement data conforming to normal distribution were represented by ± s; The measurement data that did not conform to normal distribution were represented by median and interquartile range. The classification data were expressed by the number of cases and percentage( n,%), and were compared by χ2 test or Fisher's exact test. Consistency test was represented by Kappa value. The detection of pathogenic microorganisms by the two methods and the rule of pathogen spectrum were compared and analyzed. Results:The overall positive rate of mNGS in CNS infectious diseases was higher than that of conventional methods (58.23% vs. 18.82%), and the difference was statistically significant ( P<0.01). Among the 20 samples which were both positive by the two methods, 10 cases were completely pathogenic, 5 cases were partially consistent and 5 cases were completely inconsistent. In the detection of tuberculous nervous system infection, the positive rates were 66.7%, 53.8%, 44.0%, 40.0%, 4.0% in blood T-SPOT, cerebrospinal fluid mNGS, ADA, Mycobacterium tuberculosis DNA and tuberculous specific antibody, respectively. The positive rate of acid-fast staining was 0. The positive rate of mNGS combined with conventional method was 80.8%. Conclusions:The detection rate of mNGS in CNS infection is better than that of conventional methods. However, it does not show obvious superiority in the detection rate of Mycobacterium tuberculosis associated nervous system infection. In general, mNGS detection of pathogenic bacteria is more extensive, which is conducive to a thorough and comprehensive understanding of the bacterial characteristics of central nervous system infection. The combination of the two methods can make up for the deficiency of clinical routine detection to a certain extent, and can maximize the detection rate.

Objective:To explore the clinical value of indocyanine green (ICG) fluorescence imaging technology in complex laparoscopic cholecystectomy (LC) for real-time imaging of extrahepatic bile ducts to avoid bile duct damage.Methods:The data of 90 patients with complicated gallbladder stones with cholecystitis who underwent LC from November 2018 to May 2019 at Liaoning University of Traditional Chinese Medicine Affiliated Hospital were studied. The patients were divided into the control group and the experimental group based on different imaging methods. The control group underwent conventional LC, and the experimental group underwent LC under guidance of ICG fluorescence imaging technology. ICG 5 mg were injected into a peripheral vein (elbow vein) 12 hours before operation. The pre-LC common bile duct, common hepatic duct and cystic duct recognition rates, time to establish gallbladder triangle, intraoperative blood loss, bile duct injuries and postoperative complications were determined.Results:Of the 45 patients in the experimental group, there were 18 males and 27 females. The age was (60.9±9.3) years. The body mass index (BMI) was (26.2±2.0) kg/m 2. Of the 45 patients in the control group, there were 23 males and 22 females. The age was (57.5±8.7) years. The BMI was (26.7±2.7) kg/m 2. There were no significant differences in the clinical data between the two groups ( P>0.05). In the experimental group, the common bile duct was successfully shown in 40 patients (88.9%) and the cystic duct in 34 patients (75.6%). In the control group, the common bile duct was shown in 13 patients (28.9%) and the cystic duct in 12 patients (26.7%). The time taken for the experimental group to establish the triangle of gallbladder was (33.4±9.0) min. The corresponding time for the control group was (52.7±15.0) min. The intraoperative blood loss was (15.5±5.4) ml in the experimental group and (23.0±15.6) ml in the control group. One patient in the control group, but no patients in the experimental group, had to be converted to laparotomy. The control group had 1 right hepatic duct injury and 1 common bile duct injury. Each group had 1 patient with a sub-xiphoid incision infection. No additional complications were detected after a follow-up of 3 months. The differences in pre-LC common bile duct, common hepatic duct, and cystic duct recognition rates, time to establish the gallbladder triangle, and intraoperative blood loss were significantly different between the two groups ( P<0.05). There were no significant differences in biliary tract injuries and postoperative complications rates ( P>0.05). Conclusion:Early observation of the cystic duct and common bile duct with ICG fluorescence imaging in complex LC can help prevent common bile duct damage and speed up the progress of surgery.