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

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 frequency of therapy-oriented oral radiation in Nanping, China and its distribution, and to provide a basis for the rational application of therapy-oriented oral radiation and the effective allocation of resources in Nanping. Methods A questionnaire was designed to investigate the frequency of therapy-oriented oral radiation in all oral radiation diagnosis and treatment institutions in Nanping. Results In 2021, there were 54 oral radiation diagnosis and treatment institutions and 79 oral radiation machines in Nanping. The total frequency of therapy-oriented oral radiation was 61593 visits and the radiation frequency was 19.54 visits per thousand patients. The average annual frequency of medical institutions at all levels was 721.87 to 3713.25 visits per institution; the male-to-female composition ratio of frequency of therapy-oriented oral radiation in December 2021 was 50.5%:49.5%. The proportion of radiation frequency of different devices was as follows: 38.7% (intraoral dental film), 46.5% (oral panorama), 10.3% (oral computed tomography [CT]), and 4.5% (cranial photography). The proportion of radiation frequency in patients of different ages was as follows: 17.1% (0−15 years), 48.2% (15−40 years), and 34.7% (over 40 years). The frequency of therapy-oriented oral radiation grew by 77.43%, 35.18%, and 8.16% every two years from 2015 to 2021, respectively. Conclusion The frequency level of therapy-oriented oral radiation in Nanping is at the level of Class II health care. The distribution of therapy-oriented oral radiation is highly unbalanced and is related to the level of economic development. Private healthcare institutions are growing rapidly, and public healthcare institutions of grade two and above occupy the main healthcare resources. The oral panorama accounts for the most, cranial photography accounts for the least, and oral CT is the fastest-growing portion. Therapy-oriented oral radiation is predominantly performed in the young and middle-aged populations, regardless of sex. Except for intraoral dental films, the general trend is upward.

This paper summarized Professor LI Yueqing's clinical experience in treating prostate cancer by stages from the perspective of deficiency and stasis. It is believed that the onset of prostate cancer is due to kidney deficiency， while blood stasis is the core pathogenesis， and dampness-heat， phlegm-turbid， and cancer toxins are the key pathological factors in the progression of the disease. The pathogenesis in the early stage of the disease is kidney qi depletion and dampness， heat and phlegm coagulation； in the middle stage， it is spleen and kidney depletion， phlegm coagulation and blood stasis； and in the late stage， the pathogenesis changes into yin deficiency and essence depletion， and stasis-turbid toxin obstruction. For treatment， the basic principle is to supplement and boost kidney qi， enrich and nourish the kidney yin. The main treatment methods are draining dampness， dissolving phlegm， dispelling stasis， clearing heat and resolving toxins， and the method of invigorating blood and dispelling stasis runs through the whole course of treatment. In the early stage， radical treatment is mainly used， and Longshe Yangquan Decoction （龙蛇羊泉汤） with modifications is supplemented to clear and drain dampness and heat. In the middle stage， androgen deprivation therapy is the basic treatment， and Bushen Tongqiao Decoction （补肾通窍汤） with modifications is used in combination to nourish the spleen and kidney， dissolve phlegm and dispel stasis. In the late stage， Dabuyin Pills and Liuwei Dihuang Pills （大补阴丸合六味地黄丸） with modifications is mainly used to enrich yin and supplement essence， resolve toxins and dissolve stasis， and prevent cancer recurrence.

Objective To evaluate the efficacy and safety of fluorouracil and leucovorin and oxaliplatin(FOLFOX)regimen hepatic artery infusion chemotherapy(HAIC)combined with lenvatinib(LEN)and immune checkpoint inhibitors(ICIs)in treating patients with hepatocellular carcinoma(HCC)after the occurrence of transcatheter arterial chemoembolization(TACE)refractoriness.Methods The clinical data of 54 HCC patients who developed TACE refractoriness,were admitted to the Jiangsu Provincial Cancer Hospital of China to receive FOLFOX-HAIC combined with LEN and ICIs therapy between January 2019 and December 2022,were retrospectively analyzed.The modified Response Evaluation Criteria in Solid Tumors(mRECIST)was used to statistically analyze the clinical efficacy,the Common Terminology Criteria For Adverse Events version 5.0(CTCAE 5.0)was adopted to record and evaluate the treatment-related adverse events(TRAEs).The primary endpoints were progression-free survival(PFS)and overall survival(OS),the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and safety.Results The median PFS was 11.7 months(95％CI:8.124-15.276 months),the median OS was 23.1 months(95％CI:19.508-26.692 months),the ORR was 46.3％,and the DCR was 87.0％.The most common TRAE at all levels was elevated alanine aminotransferase(51.9％),and the most common TRAE of grade 3/4 was hypertension(9.3％).No treatment-related death occurred.Conclusion For the treatment of HCC patients who developed TACE refractoriness,FOLFOX-HAIC combined LEN and ICIs is clinically safe and effective.(J Intervent Radiol,2024,33:610-615)

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.

Objective To observe the effect of Ginkgo biloba extract(GBE)on depression like behavior in post stroke depression(PSD)model rats,and explore the mechanism of regulating Toll like receptor 4/nuclear factor-κ B(TLR4/NF-κB)pathway to inhibit neuroinflammation.Methods Rats were randomly divided into 6 groups,sham,cerebral ischemia,PSD,paroxetine,low-dose Ginkgo biloba extract(GBE-L)and high-dose Ginkgo biloba extract(GBE-H)groups,10 rats in each group.Except for the sham group,middle cerebral artery occlusion(MCAO)was performed to prepare a left focal cerebral ischemia model.Except for the sham group and cerebral ischemia group,other groups were subjected to chronic unpredictable mild stress(CUMS)to establish PSD rat model for 8 weeks.After 4 weeks of CUMS,the paroxetine group,GBE-L,and GBE-H were treated with paroxetine 5 mg·kg-1,GBE 50 mg·kg-1,and GBE 100 mg·kg-1,respectively.The sham group,cerebral ischemia group,and PSD group were treated with the same volume of 0.9％NaCl and continuously administered by gavage for 28 d.After 4 weeks and 8 weeks of CUMS,the body weight and sugar preference test were measured.Levels of serum tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β)and levels of norepinephrine(NE),serotonin(5-HT),and dopamine(DA)in the cerebral cortex were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of Tlr4,Nfkb1,and nuclear factor κ B-kinase subunit β inhibitory factor(Ikbkb)in the hippocampus of rats were detected by polymerase chain reaction.The protein levels of NF-κB,nuclear factor κB inhibitory protein α(IKBα)and phosphorylation nuclear factor κB inhibitory protein α(p-IKB)in hippocampal tissue were detected by Western blot.Results The body weights of rats in the sham group,cerebral ischemia group,PSD group,paroxetine group,GBE-L group and GBE-H group were(427.10±6.36),(403.10±7.37),(310.10±9.71),(355.00±4.03),(347.90±9.88)and(391.90±5.07)g;sugar preference rate were(93.93±1.78)％,(91.57±1.03)％,(54.72±7.34)％,(88.35±4.36)％,(63.55±12.73)％and(81.04±4.31)％;the levels of NE in the cerebral cortex were(1 951.14±52.86),(1 827.27±23.63),(1 662.12±35.92),(2 033.58±72.28),(1 887.31±33.07)and(2 175.00±42.54)pg·mL-1;the levels of 5-HT in the cerebral cortex were(237.07±8.86),(226.15±10.27),(214.51±3.46),(297.13±5.79),(274.14±7.63)and(285.34±8.72)ng·mL-1;the levels of DA in the cerebral cortex were(1 531.11±47.26),(1 209.89±58.09),(1 143.15±36.31),(1 812.67±51.28),(1 651.56±31.82)and(1 853.33±20.42)pg·mL-1.Compared with the PSD group,GBE significantly increased the body weight of rats(P＜0.01)and increased the preference rate of sugar water in rats,showing the antidepressant like behavioral.GBE significantly reduced the levels of serum TNF-α,IL-1 β(all P＜0.01),increased the levels of NE,5-HT,and DA in the cerebral cortex(all P＜0.01),down regulate the mRNA levels of Tlr4,Nfkb1 and Ikbkb(P＜0.05,P＜0.01),reduced the expression of NF-κB(P＜0.01),and reduced the phosphorylation of IKBα(P＜0.01).Conclusion Ginkgo biloba extract can improve depression-like behavior in PSD model rats,and has antidepressant effect.Its mechanism is related to the inhibition of TLR4/NF-κB pathway,thus reducing neuroinflammation.

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.