BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Background::Female breast and five gynecological cancers remain substantial burden in China and worldwide. GLOBOCAN 2022 has recently updated the estimates of cancer burden. This study aims to depict the profiles of disease burden and to compare the age-specific rates of female breast and five gynecological cancers in China with those in other countries.Methods::The latest estimates of incidence and mortality of female breast and five gynecological cancers from various regions and countries were extracted from the GLOBOCAN 2022 database. We compared the proportion of total cases or deaths for cancers affecting female breast and five gynecological cancers and other tumor types in China and globally. Correlation analysis was conducted to evaluate the relationship between age-standardized incidence rate (ASIR) or age-standardized mortality rate (ASMR) and the Human Development Index (HDI). Additionally, age-specific rate curves were plotted for ten exemplary countries with different income levels.Results::Female breast and five gynecological cancers in China accounted for 30.2% of all newly diagnosed cancer cases. Breast cancer and cervical cancer are the most commonly diagnosed, with nearly 507,000 new cases, representing 23.48% of the new cases. The incidence rates of breast, uterine corpus, ovarian, and vulvar cancers were positively associated with HDI tiers. Chinese women aged 50-54 years are experiencing high incidence rates of breast, cervix uteri, corpus uteri, and ovarian cancers.Conclusions::Female breast and five gynecological cancers continue to be a significant health concern for women in China and worldwide. It is crucial to implement comprehensive prevention strategies tailored to address the increasing trend among younger individuals and reduce regional disparities.

This study was aimed at studying the phenotypic and molecular characteristics of a Salmonella Grumpensis isolate from a patient with diarrhea in Shanghai,to provide evi-dence for the prevention of salmonellosis.Biochemical identifi-cation,serum agglutination testing,antimicrobial susceptibility testing,and whole genome sequencing(WGS)were performed on isolate 2023JD76.Global Salmonella Grumpensis genome sequences were searched and downloaded for serotyping predic-tion,multilocus sequence typing(MLST),prediction of anti-microbia resistance genes and virulence genes,and phylogenetic analysis of 2023JD76.The 2023JD76 strain was identified as Salmonella Grumpensis(13,23:d:1,7)with ST2060,and was susceptible to 20 antimicrobial agents.Strain 2023JD76 carried the aminoglycoside resistance gene aac(6')-Iaa and five types of virulence genes:the adhesion genes csg and rat;the secretion and transport genes sip and inv;the typhoid toxin genes cdt and plt;the invasive gene nutrient metabolism factor mgt;and the antimicrobial peptide resistance factor mig.Global S.Grumpensis strains harbored ten types of antimicrobial resistance genes whose prevalence ranged from 58.33％to 100％.The global genome sequences of S.Grumpensis were divided into two lineages.Lineage I was dominated by ST751(88.89％,16/18),and lineage Ⅱ was dominated by ST2060(89.47％,17/19).The genome sequence of strain 2023JD76 belonged to lineage Ⅱ,and was closely related to the genome sequences from human fecal and human cerebrospinal fluid.This study provides the first report of a S.Grumpensis isolate from the stool of a patient with diarrhea in China.Considerable variability in antimicrobial resistance genes was observed among genome sequences from different sources,and the strains harbored a substantial number of virulence genes.Enhanced surveillance should be emphasized to prevent a potential risk of global dissemination.

The implementation of amplicon sequencing and metagenomic sequencing methods in the whole-genome sequen-cing for MPXV testing was compared,to provide a technical reference for sequencing,tracing,and epidemic prevention and control of MPXV.For amplicon sequencing,targeted amplification of the viral whole genome was performed on MPXV DNA,and was followed by next-generation sequencing of the amplification products.For metagenomic sequencing,next-generation sequencing was performed directly on MPXV DNA.After the sequences were obtained,software such as CLC and IGV were used to analyze the effective data percentage,sequencing depth,and whole-genome sequencing coverage under different sequen-cing depths for both sequencing methods,to evaluate sequencing quality.Nextclade was used to analyze virus typing,muta-tions,and deletions.Subsequently,the similarity and completeness of sequences obtained through both sequencing methods were further compared.On the basis of mapping to the refer-ence sequence of strain MPXV-M5312_HM12_Rivers(Gen-Bank number NC_063383.1),the percentage effective data obtained from amplicon sequencing and metagenomic sequen-cing was 99.72％and 7.54％,respectively,with a sequencing depth range of 0× to 334 839 ×,and 44 × to 1 000 ×.On the basis of a sequencing depth of 10 ×,the site coverage of the above was 90.3％and 100％,respectively.IGV was used to validate the whole-genome coverage under different sequencing depths.The depth coverage of whole-genome sites for metagenomic sequencing was uniform,whereas that of the whole-genome sites for amplicon sequencing was uneven and significantly differed.Virus typing and sequence similarity analysis indicated that the viral sequences obtained with the two sequencing methods all belonged to the Ⅱb B.1 lineage of MPXV.Comparison with the reference sequence indicated that metagenomic sequencing identified 73 nucleotide mutation sites,whereas amplicon sequen-cing identified 68 mutation sites.Further analysis demonstrated that seven common mutation sites of Ⅱb B.1 were not detected in the amplicon sequencing,and two false positive private mutation sites were identified.Amplicon or metagenomic sequencing methods thus can be flexibly used in MPXV virus whole-genome sequencing.Amplicon sequencing yields more effective data,whereas metagenomic sequencing provides better uniformity of coverage and sequence accuracy.This study provides a prelimi-nary understanding of the efficacy of each method and may serve as a technical reference for improving the success rate of whole-genome sequencing of MPXV.

Rosuvastatin(RVS)is an excellent drug with anti-inflammatory and lipid-lowering properties in the aca-demic and medical fields.However,this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia(HHcy),including high oral dosage,poor targeting,and long-term toxic side effects.In this study,we applied nanotechnology to construct a biomimetic nano-delivery system,macrophage membrane(M?m)-coated RVS-loaded Prussian blue(PB)nanoparticles(MPR NPs),for improving the bioavailability and targeting capacity of RVS,specifically to the plaque lesions associated with HHcy-induced atherosclerosis.In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4(TLR4)/hypoxia-inducible factor-1α(HIF-1α)/nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathways,reducing pyroptosis and inflammatory response in macrophages.Additionally,MPR NPs reversed the abnormal distribution of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)/ATP binding cassette transporter G1(ABCA1)/ATP binding cassette transporter G1(ABCG1)caused by HIF-1α,promoting cholesterol efflux and reducing lipid deposition.In vivo studies using apolipoprotein E knockout(ApoE-/-)mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable bio-security,and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes.These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.