Glyceryl phenylbutyrate(GPB)serves as a long-term management medication for Ornithine transcarbamylase deficiency(OTCD),effectively controlling hyperammonemia,but there is a lack of experience in using this medicine in China.This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,including a review of related literature.After diagnosis,the patient was treated with GPB,followed by efficacy follow-up and pharmacological monitoring.The 6-year and 6-month-old male patient exhibited poor speech development,disobedience,temper tantrums,and aggressive behavior.Blood ammonia levels peaked at 327 μmol/L;urine organic acid analysis indicated elevated uracil levels;cranial MRI showed extensive abnormal signals in both cerebral hemispheres.Genetic testing revealed de novo mutation in the OTC gene(c.241T＞C,p.S81P).Blood ammonia levels were approximately 43,80,and 56 μmol/L at 1,2,and 3 months after starting GPB treatment,respectively.During treatment,blood ammonia was well-controlled without drug-related adverse effects.The patient showed improvement in developmental delays,obedience,temperament,and absence of aggressive behavior.

Objective To investigate the efficacy and safety of nusinersen sodium in the treatment of children with spinal muscular atrophy(SMA).Methods A retrospective analysis was conducted on the clinical data of 50 children with 5q SMA who received nusinersen sodium treatment and multidisciplinary treatment management in Shanxi Children's Hospital from February 2022 to February 2024.Results Compared with the baseline data,67%(8/12),74%(35/47),and 74%(35/47)of the SMA children had a clinically significant improvement in the scores of Philadelphia Infant Test of Neuromuscular Disorders,Hammersmith Functional Motor Scale Expanded,and Revised Upper Limb Module,respectively,and the distance of 6-minute walking test increased from 207.00(179.00,281.50)meters to 233.00(205.25,287.50)meters(P<0.05)after nusinersen sodium treatment.Of all 50 children with SMA,24(48%)showed good tolerability after administration,with no significant or persistent abnormalities observed in 2 034 laboratory test results,and furthermore,there were no serious or immunological adverse events related to the treatment.After treatment,there was a significant change in forced vital capacity as a percentage of the predicted value in 27 children with restrictive ventilatory dysfunction,as well as a significant change in the level of 25-(OH)vitamin D in 15 children with vitamin D deficiency(P<0.05).Conclusions For children with SMA,treatment with nusinersen sodium can continuously improve the response rates of motor function scales,with good tolerability and safety.

To clarify the structural characteristics of virus communities carried by primates in the Guangdong region,and evaluate the risk of the important zoonotic virus monkeypox virus(MPXV)being introduced into China through artificially do-mesticated primates,this study conducted metagenomic research on artificially domesticated primates and performed screening for MPXV.Primate samples were collected from 20 wildlife rescue centers or zoos in 14 prefecture level cities in Guangdong Province,and the structural characteristics of virus communities carried by artificially domesticated primates were identified through Illumina sequencing.Fluorescence quantitative PCR detection of MPXV excluded the risk of MPXV being introduced through artificially domesticated primates in Guangdong Prov-ince.A total of 489 oral and pharyngeal swabs and feces from primates were collected.High-throughput sequencing indicated that the viral group structure in the feces of artificially domesti-cated primates in the Guangdong region is complex and shows regional differences.Members of Alphaflexiviridae and Vir-gaviridae,followed by members of Parvoviridae and Genomo-viridae,had the highest abundance.Subsequently,fluorescence quantitative PCR results showed that all primates from wildlife rescue centers or zoos in Guangdong Province were MPXV neg-ative.This study provides the first description of the complex viral structure characteristics of artificially domesticated primates in the Guangdong region,and elucidates the differences in vi-ral communities among artificially domesticated primates in different regions.Our findings suggested that the risk of zoonotic diseases caused by artificially domesticated primates in Guangdong Province is extremely low,and the risk of MPXV being in-troduced into China through artificially domesticated primates in Guangdong Province is zero.

Objective:Investigate the expression of thioredoxin(TXN)in pancreatic cancer and its impact on the proliferation,invasion,migration,and apoptosis of pancreatic cancer cells.Methods:By collecting pan-cancer and TCGA pancreatic cancer transcriptome and clinical data,the expression levels of the TXN gene family were analyzed.The expression levels of TXN in cancer tissues,adjacent tissues,and different cell lines were detected by fluorescence quantitative PCR(RT-qPCR)and Western blotting.The expression of the TXN gene in Panc-1 and BxPC-3 pancre-atic cancer cells was inhibited using small interfering RNA(siRNA),and control experiments were conducted with Panc-1 and BxPC-3 cells with unblocked TXN gene expression to explore the ef-fects of TXN on the proliferation,migration,invasion,and apoptosis of these two types of cells.Transcriptional data and survival outcome data were used to divide TXN expression into two groups based on the median value,and survival curves of the high and low TXN expression groups were plotted.Results:In pancreatic cancer tissues and cells,the expression level of TXN was signifi-cantly higher than that in adjacent tissues and normal cells(P＜0.05).After inhibiting the expression of TXN in pancreatic cancer cells,the proliferation rate,invasion cell number,and healing rate of pancreatic cancer cells with low TXN expression were lower than those of the control group,and their apoptosis rate was significantly higher than that of normal pancreatic cancer cells(P＜0.05).The higher the expression level of TXN in the tumors of pancreatic cancer patients,the shorter their survival time(P＜0.05).Conclusion:TXN can enhance the proliferation,migration,and invasion ability of pancreatic cancer cells and weaken the degree of cell apoptosis;the higher the expression level of TXN in pancreatic cancer tissues,the worse the prognosis.

Objective:To explore changes of acid-base metabolism in the brain tissue of patients with chronic ischemic cerebrovascular disease (CICVD) using MRI amide proton transfer-weighted (APTw) imaging.Methods:This was a cross-sectional study. From January 2021 to July 2022, thirty-nine patients with CICVD at West China Hospital, Sichuan University were retrospectively included. All patients received CT perfusion (CTP) and APTw imaging. NeuBrainCARE brain perfusion software was used to analyze the impaired perfusion sites and measure the mean transit time (MTT) and time to peak (TTP). Standard spatial matching between CTP and APTw images was performed to measure the APTw values of the same sites. For comparison with normal tissue, APTw values were measured for normal-appearing white matter (NAWM) in the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere in areas of impaired perfusion. ANOVA was used to compare the APTw values of impaired perfusion brain tissue, ipsilateral cerebral NAWM, contralateral cerebral NAWM, and ipsilateral cerebellar NAWM. The Bonferroni method was used to correct for multiple comparisons. Pearson correlation coefficient was used to analyze the correlation between APTw values and MTT and TTP in the cerebral tissue with impaired perfusion.Results:In 39 patients with CICVD, both the mean and minimum APTw values of cerebral tissue with impaired perfusion were significantly lower than those in the NAWM of the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere ( P<0.001). In the NAWM of the cerebellar hemispheres with unimpaired perfusion, both the mean and minimum APTw values were significantly higher than those in the ipsilateral cerebral hemispheres and the contralateral cerebral hemisphere ( P<0.001). Correlation analysis showed that MTT was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.90 and -0.82, P<0.001). TTP was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.86 and -0.78, P<0.001). Conclusion:APTw value can reflect acidosis in cerebral tissue with impaired perfusion in patients with CICVD.

Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.

Objective To evaluate the pharmacokinetics(PK)of tenofovir alafenamide Fumarate tablets(25 mg)in healthy Chinese subjects after single oral administration to provide a basis for bioequivalence evaluation.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design under fasting condition,while three-way crossover design under fed condition,42 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test product(T)or reference product(R)25 mg.Plasma concentration of tenofovir alafenamide and tenofovir were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by WinNonlin software(8.1 version)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The test product and the reference product under fasting study,the main PK parameters of tenofovir alafenamide were as follows:Cmax were(215.17±94.24)and(199.30±71.11)ng·mL-1;AUC0-t were(135.44±71.60)and(123.91±53.82)h·ng·mL-1;the main PK parameters of tenofovir were as follows:Cmax were(7.30±2.27)and(7.12±1.74)ng·mL-1,AUC0-t of tenofovir were(237.16±47.09)and(230.06±43.41)h·ng·mL-1,respectively.The test product and the reference product under fed study,the main PK parameters of tenofovir were as follows:Cmax were(197.69±82.19)and(197.10±110.54)ng·mL-1;AUC0-t were(197.69±82.19)and(197.10±110.54)h·ng·mL-1;the main PK parameters of tenofovir were as follows:CMax were(2.57±1.37)and(2.58±1.31)ng·mL-1;AUC0-t were(227.08±74.33)and(238.51±128.30)h·ng·mL-1,respectively.The 90％confidence interval for geometric mean ratio of Cmax,AUC0-tof T and R under fed condition were between 80.00％-125.00％,respectively.The incidence of adverse events in fasting and fed tests was 21.43％and 30.95％,respectively,and no serious adverse event was reported.Conclusion The test formulation and reference formulation of tenofovir alafenamide fumarate tablets were equivalent and was safe.

ObjectiveTo investigate the effect and possible mechanism of Sishenwan in ameliorating visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency. MethodForty male SPF-grade rats were randomly assigned into five groups： blank control， model， low- （3.51 g·kg^-1） and high-dose （7.02 g·kg^-1） Sishenwan， and Peifikang （0.54 g·kg^-1） groups. Except the blank control group， the other groups underwent maternal separation stress and Sennae Folium decoction gavage for the modeling of IBS-D due to spleen-kidney Yang deficiency. After corresponding drug interventions， the general conditions of the rats were observed， and the number of defecation pellets within 6 h and the minimum threshold of abdominal withdrawal reflex （AWR） were measured. Enzyme-linked immunosorbent assay （ELISA） was used to measure the serum levels of tumor necrosis factor （TNF）-α， gastrin （GAS）， corticosterone （CORT）， and adrenocorticotropic hormone （ACTH）. Hematoxylin-eosin （HE） staining was employed to observe pathological changes in the colon tissue. Toluidine blue staining was used to assess mast cell degranulation in the colon tissue. Western blot was performed to determine the protein levels of p38 mitogen-activated protein kinase （MAPK）， c-Jun N-terminal kinase （JNK）， transient receptor potential vanilloid 1 （TRPV1）， and protease-activated receptor 2 （PAR2） in the colon tissue. Immunohistochemistry was employed to measure the protein level of TRPV1 in the colon tissue， and immunofluorescence was used to detect the positive expression of substance P （SP） and calcitonin gene-related peptide （CGRP） in the colon tissue. ResultCompared with the blank control group， the model group showed increased number of defecation pellets within 6 h （P<0.01）， decreased minimum threshold of AWR （P<0.01）， elevated serum TNF-α level （P<0.01）， lowered levels of GAS， CORT， and ACTH （P<0.05， P<0.01）， increased mast cell degranulation rate （P<0.01）， increased positive expression of TRPV1， SP， and CGRP （P<0.05， P<0.01）， and upregulated protein levels of p38 MAPK， JNK， TRPV1， and PAR2 （P<0.01）. Compared with the model group， the high-dose Sishenwan group showed increased minimum threshold of AWR （P<0.01）， reduced defecation frequency in both the high-dose Sishenwan and Peifikang groups （P<0.05， P<0.01）， lowered TNF-α level （P<0.05， P<0.01）， elevated levels of GAS， CORT， and ACTH （P<0.05， P<0.01）， decreased mast cell degranulation rate （P<0.01）， reduced positive expression of TRPV1， SP， and CGRP （P<0.05， P<0.01）， and downregulated protein levels of p38 MAPK， JNK， TRPV1， and PAR2 （P<0.05， P<0.01）. ConclusionSishenwan can ameliorate visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome due to spleen-kidney Yang deficiency by regulating the p38 MAPK/JNK/TRPV1 signaling pathway.

Yigongsan， derived from QIAN Yi’s Key to Therapeutics of Children’s Diseases in the Song Dynasty， is a classic pediatric prescription that is included in the Catalogue of Ancient Classic Prescriptions （the Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine in 2022. This paper verifies and analyzes the historical origin， composition， dosage， processing， decoction method and efficacy of Yigongsan by systematically combing ancient books and modern documents. As a result， Yigongsan is composed of five herbs： Panax ginseng， Poria cocos， Atractylodes macrocephala， Citrus reticulata and Glycyrrhiza uralensis， of which P. cocos should be peeled， A. macrocephala is fried with soil， G. uralensis is roasted with honey while P. ginseng and C. reticulata are raw products. According to the dosage of ancient and modern times， each medicinal herb must be ground into fine powder， 1.6 g for each， added with 300 mL of water， 5 pieces of Zingiber officinale， and 2 Ziziphus jujuba， decocted together to 210 mL， and taken before meals. In ancient books， Yigongsan is used to treat vomiting， diarrhea， spleen and stomach deficiency， chest and abdominal distension， and lack of appetite， etc. Modern research showed that Yigongsan could also be used in the diseases of immune system， respiratory system， blood system， etc.， involving infantile anorexia， asthma， anemia， tumors and so on.

Objective To investigate the effects of Fuzheng Quxie Prescription(mainly with the actions of supporting healthy qi and dispelling pathogens)combined with neoadjuvant chemotherapy on tumor recurrence,serum thymidine kinase 1(TK1)level and immune function in patients with triple-negative breast cancer(TNBC).Methods Eighty patients with TNBC of qi and yin deficiency type were randomly divided into a combination group and a control group,with 40 patients in each group.The control group was treated with AC-T sequential chemotherapy(Doxorubicin combined with Cyclophosphamide plus sequential Docetaxel),and the combination group was treated with Fuzheng Quxie Prescription on the basis of treatment for the control group.One course of treatment covered 21 days,and the two groups were treated for 4 consecutive courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,levels of tumor markers of carbohydrate antigen 125(CA125),carbohydrate antigen 153(CA153)and TK1,and T lymphocyte subset levels in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and tumor metastasis and recurrence in the two groups were compared.Results(1)After 4 courses of treatment,the total effective rate of the combination group was 87.50%(35/40),and that of the control group was 67.50%(27/40),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the combination group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the KPS scores were significantly increased compared with those before treatment(P＜0.05),and the decrease of TCM syndrome scores and the increase of KPS scores in the combination group were significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the serum CA125,CA153 and TK1 levels of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of serum CA125,CA153 and TK1 levels in the combination group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio in the two groups were significantly increased compared with those before treatment(P＜0.05),and the CD8+ level was significantly decreased compared with that before treatment(P＜0.05).The post-treatment intergroup comparison showed that the increase of the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio as well as the decrease of the CD8+ level in the combination group was all significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)The one-year follow-up showed that the tumor recurrence rate and tumor metastasis rate in the combination group were 7.50%(3/40)and 12.50%(5/40)respectively,significantly lower than 25.00%(10/40)and 35.00%(14/40)in the control group,and the differences were statistically significant when comparing between the two groups(P＜0.05).Conclusion The combination of neoadjuvant chemotherapy with Fuzheng Quxie Prescription has a better therapeutic effect on TNBC patients with qi and yin deficiency syndrome,which can effectively improve the immune function of the patients,decrease the level of serum tumor markers,improve the quality of life of the patients,and reduce the incidence of tumor recurrence and metastasis.