ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

Objective To investigate the effect and mechanism of Yiguan Decoction(YGJD)on the efficacy of M1 bone marrow-derived macrophages(M1-BMDMs)in the treatment of rats with liver cirrhosis induced by 2-AAF/CCl4.Methods BMDMs were isolated and induced into M1-BMDMs by lipopolysaccharide.A total of 50 male Wistar rats were randomly divided into normal group with 5 rats and model group with 45 rats.The rats for modeling were given subcutaneous injection of 50%CCl4 twice a week.Since week 7,the rats for modeling were randomly divided into model group(M group),YGJD group,M1-BMDM group,M1-BMDM+YGJD group,and sorafenib(SORA)group,and they were given subcutaneous injection of 30%CCl4 to maintain the progression of liver cirrhosis and intragastric administration of 2-AAF.CCR2 inhibitors were added to the drinking water,and each group was given the corresponding intervention.Related samples were collected at week 9.The rats were observed in terms of serum liver function parameters,liver pathology,hydroxyproline(Hyp)content in liver tissue,hepatic stellate cell activation,hepatic fibrosis and inflammation factors,and the expression levels of molecules associated with the Wnt signaling pathway.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the M group,the M1-BMDM+YGJD group had significant reductions in the serum levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin(TBil)(all P<0.05)and a significant increase in the content of albumin(Alb)(P<0.05),and compared with the M1-BMDM group,the M1-BMDM+YGJD group had a significant reduction in the serum level of TBil(P<0.05)and a significant increase in the serum level of Alb(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in the expression levels of CD68 and TNF-α(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in Hyp content and Sirius red positive area(P<0.05).As for the non-canonical Wnt signaling pathway molecules,compared with the M1-BMDM group,the M1-BMDM+YGJD group had significantly lower mRNA and protein expression levels of Wnt5a(P<0.05)and mRNA expression level of Fzd2(P<0.05),as well as significant reductions in the mRNA expression levels of Wnt4,Wnt5b,and Fzd3(P<0.05),while there were no significant changes in the mRNA expression levels of the canonical Wnt signaling pathway molecules β-catenin,LRP5,LRP6,Fzd5,and TCF.Conclusion YGJD can enhance the therapeutic effect of M1-BMDMs on rats with liver cirrhosis induced by 2-AAF/CCl4,possibly by inhibiting the non-canonical Wnt5a/Fzd2 signaling pathway,which provides new ideas for the synergistic effect of traditional Chinese medicine on M1-BMDMs in the treatment of liver cirrhosis.

Objective:To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation.Methods:Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m 2) and cisplatin (60 mg/m 2) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results:The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95% CI: 74.0% to 94.8%) and 50.3% (95% CI: 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95% CI: 88.9% to 100.0%) and 58.2% (95% CI: 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95% CI: 74.2% to 94.9%) and 53.5% (95% CI: 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion:The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.

Objective:To retrieve, evaluate, and integrate the best evidence for prevention of hemodialysis catheter thrombosis, so as to provide evidence-based basis for catheter thrombosis prevention in hemodialysis patients.Methods:Guidelines, clinical decisions, evidence summaries, systematic reviews, and expert consensus on the prevention of hemodialysis catheter thrombosis were systematically searched on Guidelines International Network, Scottish Intercollegiate Guidelines Network, Agency for Healthcare Research and Quality, Registered Nurses' Association of Ontario, National Institute for Health and Clinical Excellence, UpToDate, British Medical Journal (BMJ) Best Practice, Joanna Briggs Institute Evidence-Based Health Care Center Database, European Renal Association, National Kidney Foundation, UK Kidney Association, Canadian Society of Nephrology, Japanese Society for Dialysis Therapy, Medlive, Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, VIP, and Wanfang Data and Chinese Biomedical Database. The search period was from database establishment to March 31, 2023. Investigators conducted quality evaluations separately and extracted and summarized evidence based on the theme.Results:A total of 16 articles were included, including five clinical decisions, four guidelines, two evidence summaries, and five expert consensuses. Finally, 15 best pieces of evidence were formed, including four themes of indwelling dialysis catheters, anticoagulation strategies, flushing and sealing techniques, and daily management.Conclusions:Nursing staff should choose the best evidence for preventing thrombosis in hemodialysis catheters based on clinical situations, reduce the occurrence of catheter thrombosis, extend the usage time of catheters, and improve patient outcomes.

Objective To explore the application value of RMNES combined with comprehensive rehabilitation for consciousness impairment caused by senile brain injury.Methods A retrospec-tive analysis was conducted on 160 elderly patients with consciousness disorders caused by brain injury admitted in our hospital between January 2020 and November 2023.According to treatment regiments,they were divided into comprehensive rehabilitation group(Group Ⅰ,53 cases),com-prehensive rehabilitation followed by RMNES group(Group Ⅱ,54 patients),and simultaneous indoor comprehensive rehabilitation and RMNES(Group Ⅲ,53 patients).At 1 week after treat-ment,electroencephalogram(EEG)grade,brainstem auditory induction(BAEP)grade,cerebral hemodynamic parameters[including relative cerebral blood flow(rCBF),relative cerebral blood volume(rCBV),and mean blood flow velocity(Vm)],Disability Rating Scale(DRS)score,and Glasgow Coma Scale(GCS)score were compared among the three groups.Results After 1 week of treatment,the ratios of EEG grade Ⅰ,EEG grade Ⅱ and BAEP grade Ⅰ,rCBV,rCBF and Vm values and GCS score were increased,while the ratios of EEG grade V and BAEP grade Ⅲ,and DRS score were decreased when compared with the levels before treatment(P＜0.05).Significant differences were observed in EEG grade and BAEP grade among the 3 groups after 1 week of treatment(P＜0.01);Group Ⅲ had obviously higher rCBV,rCBF,Vm and GCS score and lower DRS score than Groups Ⅰ and Ⅱ(P＜0.05).There was no statistical difference in the incidence of adverse reactions in Groups Ⅰ,Ⅱ and Ⅲ(3.77％vs 7.41％vs 7.55％,x2=0.830,P=0.660).Conclusion Simultaneous indoor comprehensive rehabilitation and RMNES treatment achieves more significant efficacy for elderly patients with brain injury-caused consciousness disorders,and it can improve electrophysiological activities of brain nerves,enhance cerebral hemodynamics,and promote the recovery of consciousness.

Objective To investigate the genetic diversity and genetic differentiation of different geographical isolates of Gohieria fusca.. Methods G. fusca isolates were sampled from Wuhu (WH), Bengbu (BB) and Bozhou cities (BZ) of Anhui Province and Jiaxing City of Zhejiang Province (JX). Mitochondrial cytochrome b (Cytb) and ribosomal internal transcribed spacer (ITS) genes were amplified in WH, BB, BZ and JX isolates of G. fusca using PCR assay. The gene sequences were edited and aligned using the software Chromas 2 and DNASTAR 1.00, and the haplotype, haplotype diversity (Hd) and nucleotide polymorphism (Pi) of each isolate were calculated using the software DnaSP 5.10.00. The genetic differentiation among isolates (F_st) and gene flow value (N_m) were estimated using the software MEGA 10.2, and a phylogenetic tree was built. Tests of neutrality and analysis of molecular variance (AMOVA) were performed using the software Arlequin 3.1 and a haplotype network was built based on the Median-Joining network using the software Network 10.2. Results PCR assay showed that the sizes of the Cytb and ITS genes were 372 bp and 1 301 to 1 320 bp, respectively. All four isolates of G. fusca presented high genetic diversity based on mitochondrial Cytb and ITS genes (Hd = 0.804, Pi = 0.006 91). AMOVA showed genetic differentiation among geographical isolates of G. fusca (F_st = 0.202 40, P < 0.05), and the genetic variation was mainly caused by intra-population variations (79.76%). Gene flow analysis showed a high level of gene flow among G. fusca isolates (N_m > 1). Tests of neutrality based on Cytb gene measured a Tajima’s D value of −1.796 31 (P < 0.05) and a Fu’s FS value of −3.293 98 (P < 0.05) in WH isolate of G. fusca, indicating population expansion in WH isolate of G. fusca. Haplotype network analysis and phylogenetic analysis revealed no remarkable geographical distribution pattern among different geographical isolates of G. fusca. All four isolates of G. fusca presented high genetic diversity (Hd = 0.985, Pi = 0.011 97). AMOVA showed moderate level of genetic differentiation between four isolates (F_st = 0.104 62, P < 0.05). The tests of neutrality based on ITS genes measured a Tajima’s D value of −6.088 20 and a Fu’s FS value of −1.935 99 (both P > 0.05) in the whole isolate of G. fusca, indicating no obviously population expansion. Conclusions The four geographical isolates of G. fusca have high genetic diversity and remarkable genetic differentiation. Since a high level of gene flow is detected among different geographical isolates of G. fusca, no obvious geographical distribution pattern of G. fusca is found.

Objective To investigate the effect of blood group serology and polymerase chain reaction with sequence-specific primers (PCR-SSP) on identification and genotyping of ambiguous ABO blood group. Methods Eighty suspicious ABO blood group samples were identified by serology and polymerase chain reaction with sequence-specific primers (PCR-SSP). The final blood group type and the strategy of the transfusion of each case were determined according to the results of serology and PCR-SSP. Results 40 cases were confirmed to be subtypes, and the remaining 40 cases were normal types with weakened antigens or missing antibodies due to other reasons. The results of molecular genetic blood group typing based on PCR-SSP were 41 cases of subtypes (There were 3 discrepancies between two methods: one was Ael identified by serological methods, while its gene type was O2O2; one was common type O, while its gene type was BO1; one was type A, while its gene type was AB.) and 39 cases of normal ones. Conclusion Genotyping technology combined with serological typing has an important significance in identification of ABO blood groups.
ABO Blood-Group System/genetics* ; Genotype ; Polymerase Chain Reaction ; Antibodies ; DNA Primers

BACKGROUND: Massive bleeding is the main concern for the management of placenta percreta (PP). Intra-abdominal aortic balloon occlusion (IABO) is one method for pelvic devascularization, but the efficacy of IABO is uncertain. This study aims to investigate the outcomes of IABO in PP patients. METHODS: We retrospectively reviewed the clinical data of PP cases from six tertiary centers in China between January 2011 and December 2015. PP cases with/without the use of IABO were analyzed. Propensity score matching analysis was performed to reduce the effect of selection bias. Postpartum hemorrhage (PPH) and the rate of hysterectomy, as well as neonatal outcomes, were analyzed. RESULTS: One hundred and thirty-two matched pairs of patients were included in the final analysis. Compared with the control group, maternal outcomes, including PPH (68.9% vs. 87.9%, χ2 = 13.984, P < 0.001), hysterectomy (8.3% vs. 65.2%, χ2 = 91.672, P < 0.001), and repeated surgery (1.5% vs. 12.1%, χ2 = 11.686, P = 0.001) were significantly reduced in the IABO group. For neonatal outcomes, Apgar scores at 1 minute (8.67 ± 1.79 vs. 8.53 ± 1.68, t = -0.638, P = 0.947) and 5 minutes (9.43 ± 1.55 vs. 9.53 ± 1.26, t = 0.566, P = 0.293) were not significantly different between the two groups. CONCLUSIONS IABO can significantly reduce blood loss, hysterectomies, and repeated surgeries. This procedure has not shown harmful effects on neonatal outcomes.
Aorta ; Balloon Occlusion/methods* ; Blood Loss, Surgical ; Female ; Humans ; Hysterectomy ; Infant, Newborn ; Placenta Accreta/surgery* ; Placenta Previa/surgery* ; Postpartum Hemorrhage ; Pregnancy ; Retrospective Studies

Objective: Network pharmacology combines drug and disease targets with biological information networks based on the integrity and systematicness of the interactions between drugs and disease targets. This study aims to explore the molecular basis of Hanshi Zufei formula for treatment of COVID-19 based on network pharmacology and molecular docking techniques. Methods: Using TCMSP, the chemical constituents and molecular targets of Atractylodis Rhizoma, Citri Reticulatae Pericarpium, Magnoliae Officinalis Cortex, Pogostemonis Herba, Tsaoko Fructus, Ephedrae Herba, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, and Arecae Semen were investigated. The predicted targets of novel coronavirus were screened using the NCBI and GeneCards databases. To further screen the drug-disease core targets network, the corresponding target proteins were queried using multiple databases (Biogrid, DIP, and HPRD), a protein interaction network graph was constructed, and the network topology was analyzed. The molecular docking studies were also performed between the network's top 15 compounds and the coronavirus (SARS-CoV-2) 3CL hydrolytic enzyme and angiotensin conversion enzyme II (ACE2). Results: The herb-active ingredient-target network contained nine drugs, 86 compounds, and 49 drug-disease targets. Gene ontology (GO) enrichment analysis resulted in 1566 GO items (P < 0.05), among which 1438 were biological process items, 35 were cell composition items, and 93 were molecular function items. Fourteen signal pathways were obtained by enrichment screening of the KEGG pathway database (P < 0.05). The molecular docking results showed that the affinity of the core active compounds with the SARS-CoV-2 3CL hydrolase was better than for the other compounds. Conclusion: Several core compounds can regulate multiple signaling pathways by binding with 3CL hydrolase and ACE2, which might contribute to the treatment of COVID-19.

Objective:To investigate the effect of placenta previa attached to cesarean scar for adverse pregnant outcomes in patients with or without placenta accreta spectrum disorders (PAS).Methods:The clinical information of patients with cesarean section history and placenta previa during the perioperative period at Peking University First Hospital from January 1st, 2015 to December 31st, 2020 were collected retrospectively. There were 53 cases without PAS and 172 cases with PAS, 153 cases with abnormally invasive placenta (containing placenta increta and placenta percreta) and 72 cases without PAS or with placenta accreta. The pregnant outcomes including rate of postpartum hemorrhage, transfusion, hysterectomy between the above groups were compared. Multivariate analysis was performed to study the factors significantly associated with PAS.Results:Pregnant women with PAS were at higher risk of adverse pregnant outcomes than those without PAS. Patients with PAS had higher incidences of hysterectomy [12.2% (21/172) vs 0(0/53); P=0.005], postpartum hemorrhage [60.5% (104/172) vs 5.7% (3/53); P<0.01] and blood transfusion [66.9% (115/172) vs 7.5% (4/53); P<0.01]. In the subgroup analysis stratified by the type of PAS, patients with abnormally invasive placenta were at higher risk of hysterectomy [13.7% (21/153) vs 0 (0/72); P<0.01], postpartum hemorrhage [66.7% (102/153) vs 6.9% (5/72); χ2 =70.873, P<0.01] and blood transfusion [74.5% (114/153) vs 6.9% (5/72); χ2 =90.869, P<0.01]. After multiple logistic regression, the type of creta had the positive relation with postpartum hemorrhage ( OR=27.622, 95% CI:9.873~77.280; P<0.01) and blood transfusion ( OR=36.912, 95% CI:13.239~102.922; P<0.01). There were no significant correlations between adverse pregnant outcomes and the type of placenta previa or the times of cesarean section (all P>0.01). Conclusions:Placenta previa attached to cesarean scar without PAS or with placenta accreta could not act as the factor of predicting adverse pregnant outcomes in clinic. Placenta previa attached to cesarean scar with placenta increta or placenta percreta could increase the risk of adverse pregnant outcomes.