Objective:To investigate improvement effect of astragalus polysaccharides(APS)on recurrent spontaneous abor-tion(RSA)in rats and its mechanism.Methods:Pregnant rats were randomly grouped into control group,RSA group,dexamethasone group,APS low,medium,high doses groups and LY294002 group.A RSA rat model was constructed,uterine organ index and embryo loss rate were calculated.HE staining was applied to observe histopathology changes of decidua.ELISA was applied to detect serum levels of estradiol(E2),progesterone(P),prolactin(PRL),cytokines such as IFN-γ,TNF-α,IL-4 and IL-10.Immunohisto-chemistry was applied to detect expression of decidua progesterone receptor(PR).Western blot was applied to detect expression of PI3K/AKT signaling pathway proteins of decidua.Results:Compared with control group,desquamated cells of rats in RSA group exhibit edema,disordered arrangement,nuclear pyknosis and disappearance,and decidua reduced interstitial blood vessels,uterine organ index,serum IL-4,IL-10,E2,P,PRL levels,decidua PR,p-PI3K,p-AKT expressions were obviously reduced,embryo loss rate,IFN-γ and TNF-α levels were obviously increased(P<0.05);compared with RSA group,morphology of decidual cells and interstitial blood vessels in dexamethasone group and APS low,medium and high doses groups were improved,uterine organ index,serum IL-4,IL-10,E2,P,PRL levels,decidua PR,p-PI3K,p-AKT expressions were obviously increased,embryo loss rate,serum IFN-γ and TNF-α levels were obviously reduced(P<0.05);LY294002 reversed improvement effect of high-dose APS on adverse pregnancy out-comes in RSA rats(P<0.05).Conclusion:APS can reduce miscarriage rate of RSA rats,regulate Th1/Th2 balance,whose mecha-nism may be related to activation of PI3K/AKT.

Objective:To investigate improvement effect of astragalus polysaccharides(APS)on recurrent spontaneous abor-tion(RSA)in rats and its mechanism.Methods:Pregnant rats were randomly grouped into control group,RSA group,dexamethasone group,APS low,medium,high doses groups and LY294002 group.A RSA rat model was constructed,uterine organ index and embryo loss rate were calculated.HE staining was applied to observe histopathology changes of decidua.ELISA was applied to detect serum levels of estradiol(E2),progesterone(P),prolactin(PRL),cytokines such as IFN-γ,TNF-α,IL-4 and IL-10.Immunohisto-chemistry was applied to detect expression of decidua progesterone receptor(PR).Western blot was applied to detect expression of PI3K/AKT signaling pathway proteins of decidua.Results:Compared with control group,desquamated cells of rats in RSA group exhibit edema,disordered arrangement,nuclear pyknosis and disappearance,and decidua reduced interstitial blood vessels,uterine organ index,serum IL-4,IL-10,E2,P,PRL levels,decidua PR,p-PI3K,p-AKT expressions were obviously reduced,embryo loss rate,IFN-γ and TNF-α levels were obviously increased(P<0.05);compared with RSA group,morphology of decidual cells and interstitial blood vessels in dexamethasone group and APS low,medium and high doses groups were improved,uterine organ index,serum IL-4,IL-10,E2,P,PRL levels,decidua PR,p-PI3K,p-AKT expressions were obviously increased,embryo loss rate,serum IFN-γ and TNF-α levels were obviously reduced(P<0.05);LY294002 reversed improvement effect of high-dose APS on adverse pregnancy out-comes in RSA rats(P<0.05).Conclusion:APS can reduce miscarriage rate of RSA rats,regulate Th1/Th2 balance,whose mecha-nism may be related to activation of PI3K/AKT.

Objective·To investigate the clinical manifestations and immunophenotypic features of peripheral T-cell lymphoma,not otherwise specified(PTCL-NOS),involving the oral cavity.Methods·The medical histories and pathology records of patients diagnosed with oral PTCL-NOS in the Department of Oral Mucosal Diseases of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,between August 2020 and August 2024 were retrospectively analyzed.In addition,5 databases,including PubMed,Web of Science,Embase,Scopus,and CNKI,were searched,and relevant cases reported internationally from January 2014 to September 2024 were reviewed.Results·A total of 20 oral PTCL-NOS cases were included,comprising 11 males(55.0%)and 9 females(45.0%).The patients' ages at initial diagnosis ranged from 25 to 77 years,with a mean age of(52.53±12.94)years.The most common sites were the tongue(25.0%),palate(25.0%),and buccal mucosa(20.0%).Nineteen cases(95.0%)had no B symptoms.The cases were positive for CD3(19/19),CD4(11/13),CD8(7/12),CD2(5/6),CD7(5/5),TIA-1(6/7),GB(9/13),perforin(4/6).EBER expression was negative(8/8).The Ki-67 proliferation index was≥60%in 85%of cases.Conclusions·Oral PTCL-NOS is extremely rare and has an aggressive clinical behavior.The oral manifestation presents as deep and large mucosal ulcers with uneven bases,and nodules can be palpable.The pathological features are heterogeneous.Immunophenotype detection is useful for early diagnosis and classification.It is essential for stomatologists to enhance their awareness of this malignancy to avoid delayed diagnosis and treatment.

Objective·To investigate the clinical manifestations and immunophenotypic features of peripheral T-cell lymphoma,not otherwise specified(PTCL-NOS),involving the oral cavity.Methods·The medical histories and pathology records of patients diagnosed with oral PTCL-NOS in the Department of Oral Mucosal Diseases of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,between August 2020 and August 2024 were retrospectively analyzed.In addition,5 databases,including PubMed,Web of Science,Embase,Scopus,and CNKI,were searched,and relevant cases reported internationally from January 2014 to September 2024 were reviewed.Results·A total of 20 oral PTCL-NOS cases were included,comprising 11 males(55.0%)and 9 females(45.0%).The patients' ages at initial diagnosis ranged from 25 to 77 years,with a mean age of(52.53±12.94)years.The most common sites were the tongue(25.0%),palate(25.0%),and buccal mucosa(20.0%).Nineteen cases(95.0%)had no B symptoms.The cases were positive for CD3(19/19),CD4(11/13),CD8(7/12),CD2(5/6),CD7(5/5),TIA-1(6/7),GB(9/13),perforin(4/6).EBER expression was negative(8/8).The Ki-67 proliferation index was≥60%in 85%of cases.Conclusions·Oral PTCL-NOS is extremely rare and has an aggressive clinical behavior.The oral manifestation presents as deep and large mucosal ulcers with uneven bases,and nodules can be palpable.The pathological features are heterogeneous.Immunophenotype detection is useful for early diagnosis and classification.It is essential for stomatologists to enhance their awareness of this malignancy to avoid delayed diagnosis and treatment.

BACKGROUND:"Tendon off-position"is a disease name included in the International Classification of Diseases 11th Revision,and also a clinical indication of manipulation,acupuncture and other treatments.However,its specific mechanism is still unclear.It is urgent to establish an animal model that can reflect the clinical and pathological characteristics of"tendon off-position,"so as to further study the mechanism of effective clinical treatments. OBJECTIVE:To establish an animal model of"tendon off-position"in rats based on isometric contraction of skeletal muscles,and to explore the changes of skeletal muscle function and morphological phenotype after"tendon off-position." METHODS:Sixty rats were randomly divided into control group,static-loading group and extra loading group,with twenty rats in each group.Rats in the control group were kept normally without treatment.In the latter two groups,the rats were fixed by the self-made static-loading modeling device and a static-loading(the body mass of each rats was applied as the static-loading)was applied to cause sustained isometric contraction of the upper limb muscles.Then,animal models of"tendon off-position"were successfully established.In the extra loading group,50%of the body mass was added to the ankle joint after modeling.The skeletal muscle samples were harvested at 2 and 4 weeks after modeling.The changes of limb grip strength,wet mass of skeletal muscle,and serum levels of creatine kinase-muscle and lactate dehydrogenase A were measured,and the changes of skeletal muscle histomorphology and ultrastructure were observed. RESULTS AND CONCLUSION:At 2 weeks after modeling,the rats in the static-loading group and extra loading group showed significantly decreased grip strength and wet muscle mass,significantly increased serum levels of creatine kinase-muscle and lactate dehydrogenase A,and abnormal muscle fiber morphology and structure accompanied by a large number of deposited collagen fibers.Electron microscopy results showed that the structure of myofibrils was disordered,the Z-line was distorted,and the light and dark boundaries were blurred.At 4 weeks after modeling,the grip strength of the model rats was increased compared with that at 2 weeks,the serum creatine kinase-muscle and lactate dehydrogenase A levels were decreased,and the changes of muscle fiber morphology and ultrastructure were recovered to varying degrees.It is suggested that the rat skeletal muscle injury model based on continuous isometric contraction of skeletal muscle can well reflect the pathological characteristics of"tendon off-position"at 2 weeks,and can be used to study the mechanism of acupuncture and manipulation in the treatment of"tendon off-position."

Objective To explore the solvent effect on the chromatographic retention performance by RP-HPLC in traditional Chinese medicine analysis.Methods Five traditional Chinese medicines were selected to determin by HPLC according to the requirements of each medicinal content determination item in Chinese pharmacopoeia(Vol.Ⅰ,2020),they were gentiopicroside-Radix gentianae,syringin-Acanthopanax enticosus,rosin diglucoside-Eucommia ulmoides,aesculin-Fraxinus Cortex,and adenosine-Cordyceps sinensis respectively.The effect of sample solvent in RP-HPLC was explored preliminarily on the chromatographic peak abnormalities and some solutions were proposed.Results The abnormal chromatographic retention behavior of the five traditional Chinese medicine components were characterized by retention time drift,peak broadening,extending and splitting,the fundamental reason for the above abnormal phenomenons was that there was a certain mismatch between the sample solvent and the mobile phase,leading to different existing forms of the sample between the sample solvent and the mobile phase(Solvent Effect).The results showed that the mobile phase or similar to mobile phase solution was a preferred method to reduce and eliminate solvent effect.In addition,reducing the injection volume or using the solvent effect eliminator can also be used as auxiliary means.Conclusion Solvent effect can cause abnormal peak shape,and had an influence on the accuracy of qualitative and quantitative results,it should be taken seriously in daily Chinese medicine analysis work.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

Objective:To investigate the efficiency of biochemical screening and hotspot gene screening in the detection of neonatal inherited metabolic diseases.Methods:This was a prospective multi-center study.The study was carried out on 21 442 neonatal samples collected from 12 hospitals in 10 provinces from November 2020 to November 2021.The results of biochemical screening and hotspot gene screening were analyzed jointly.Biochemical screening methods included glucose-6-phosphate dehydrogenase deficiency enzyme activity assay and neonatal tandem mass spectrometry.Genetic screening analysis involved 135 genes associated with 75 neonatal diseases.Results:Of all the 21 442 neonates enrolled in the study, 21 205 were subject to biochemical screening.A total of 813 cases were positive in the initial screening, and 0.45% of them (95 cases) were diagnosed after recall.All the 21 442 neonates underwent gene screening.About 168 positive cases were detected in the initial screening, and 0.73% (156 cases) of them were confirmed finally.Biochemical and genetic screening improved the detection sensitivity of such diseases as primary carnitine deficiency, neonatal intrahepatic cholestasis caused by citrin deficiency, and 2-methylbutyrylglycinemia.Moreover, biochemical and genetic screening enabled the detection of more diseases, including the common single-gene genetic diseases such as thalassemia and Wilson disease.Conclusions:In neonatal screening, the combination of biochemical screening and gene screening expands the number of diseases detected and improve screening efficiency.

Objective:To investigate the incidence, clinical characteristics and prognosis of ornithine transcarbamylase deficiency(OCTD) in newborns in Zhejiang Province.Methods:A retrospective research was conducted.A total of 4 261 036 newborns from Department of Genetics and Metabolism, Children′s Hospital, Zhejiang University School of Medicine, between January 2009 and December 2021 were screened for inherited metabolic disorders using tandem mass spectrometry.OCTD was confirmed by urine organic acid and OTC gene analysis.Patients with OTCD received guidance on diet and lifestyle management, and were treated with citrulline and arginine.Long-term follow-up was performed.Their growth and intellectual development were evaluated. Results:A total of 7 patients with OCTD were diagnosed, with an incidence of 1.6/1 million.All patients were males.Two patients had neonatal-onset OCTD, and the other 5 had late-onset OCTD.Symptoms occurred several times in 6 patients, inducing hyperammonemia and hepatic impairment.One patient had no clinical manifestation.One patient died in the neonatal period.Blood citrulline levels were decreased in 7 patients to varying degrees.Uracil levels were increased in 4 patients, and 1 of them was complicated with elevated orotic acid levels.All patients had hemizygote variations in the OTC gene, including 6 missense variations(c.604C>T, c.386G>A, c.779T>C, c.1019C>T, c.594C>G, c.931G>A) and 1 intron variation(c.514-35C>G). Two variants(c.594C>G, c.514-35C>G) were never reported previously. Conclusions:The OTCD incidence by newborn screening is low with 1.6/1 million in Zhejiang province.All patients are males and present hypocitrullinemia.The clinical manifestations of OTCD are highly heterogeneous.The neonatal-onset form is severe and survivors always suffer serious sequelae.The late-onset form is mostly manifested with hyperammonemia and hepatic impairment.There may be association between phenotype and genotype.Two novel OTC variants are identified, which further expands the mutational spectrum.

Objective:To explore the genetic causes of abnormal isovaleryl carnitine (C5) metabolism in newborns.Methods:Retrospective study.The screening and clinical follow-up data of 34 neonates with elevated C5 levels shown by the tandem mass spectrometry test in Children′s Hospital, Zhejiang University School of Medicine from January 2018 to December 2021 were collected.Afterwards, their ethylenediaminetetraacetic acid (EDTA) anticoagulant venous blood was collected to extract genomic DNA.A total of 79 genes related to genetic metabolic diseases, such as ACADSB, IVD and ACADM, were captured by liquid-phase capture technology.High-throughput sequencing and bioinformatics analysis were used to acquire gene variation information and the genes were categorized by American College of Medical Genetics and Genomics classification standard.According to the results of genetic analysis, the newborns with C5 elevation were divided into 3 groups: non-mutation group(11 cases), ACADSB mutation group(16 cases) and IVD mutation group(7 cases). Wilcoxon rank sum test was performed to analyze the difference between these groups. Results:Among 34 neonates, 6 ACADSB variants were detected in 16 cases, and 2 of them [c.461G>A (p.G154E), c.746delC(p.P249Lfs*15)] were novel variants.Eleven IVD variants were detected in 7 cases, and 7 of them [c.118A>G(p.N40D), c.296-10C>G, c.302A>G(p.Y101C), c.537G>A(p.M179I), c.667C>T(p.R223W), c.983A>G(p.K328R), c.1147+ 5G>A] were never reported before.There was no significant difference in the C5 concentration in initial screening among the three groups ( P>0.05). Conclusions:Mutations in ACADSB and IVD genes are the main causes of augmented C5 levels in neonatal screening.For newly discovered genetic variants, functional prediction by multiple bioinformatics analysis software is recommended.And it is also important to carry out clinical follow-up and evaluation.