ObjectivePremenstrual syndrome （PMS） is a cyclical psychosomatic disorder associated with neuroendocrine dysfunction and dysregulation of monoamine neurotransmitters. Yiqi Weixue prescription （YQWX）， with both medicinal and edible value， shows the potential in alleviating PMS， yet its multi-target synergistic mechanism remains unclear. This study aims to explore the multi-target synergistic mechanism of YQWX in alleviating premenstrual syndrome through transcriptomics. MethodsThe rat model of PMS was established by progesterone injection combined with restraint stress. A total of 49 female Wistar rats were randomized into a normal group， a solvent group， a model group， low-， medium-， and high-dose （359， 718， 1 436 mg·kg^-1， respectively） YQWX groups， and a positive control （Kuntai capsules， 540 mg·kg^-1） group. After two weeks of intervention， behavioral changes were assessed by open field， forced swimming， and sucrose preference tests. Serum levels of 5-hydroxytryptamine （5-HT）， norepinephrine （NE）， and brain-derived neurotrophic factor （BDNF）， as well as serum levels of interleukin-6 （IL-6） and interleukin-1β （IL-1β）， were measured by enzyme-linked immunosorbent assay （ELISA）. Hippocampal RNA was extracted for transcriptomic sequencing， followed by screening of differentially expressed genes （DEGs）， and then Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed. The expression of key genes was validated by quantitative Real‑time polymerase chain reaction （Real-time PCR）， ELISA， and immunohistochemical （IHC） staining. ResultsCompared with the solvent group， the model group showed decreases in total movement distance， active time， rearing frequency， central zone duration， and grid line crossings in the open field test （P<0.01）， increases in peripheral zone duration and immobility time in the forced swimming test （P<0.01）， a reduced sucrose preference rate （P<0.01）， declined serum levels of 5-HT， NE， and BDNF （P<0.01）， and elevated serum levels of IL-6 and IL-1β （P<0.01）. Compared with the model group， the medium and high-dose YQWX groups exhibited significant improvements in the above behavioral parameters （P<0.05， P<0.01）. The medium-dose YQWX group showed restoration of 5-HT and BDNF levels （P<0.05）， and the high-dose YQWX group showed restoration of NE levels （P<0.01）. All YQWX groups reduced serum IL-6 and IL-1β levels （P<0.01）. Transcriptome sequencing identified 513 DEGs in the model group compared with the solvent group and 512 DEGs in the YQWX group compared with the model group. Enrichment analyses pointed out key pathways related to platelet activation， complement， coagulation cascade， inflammation， and neuroendocrine regulation. Experimental validation demonstrated that YQWX upregulated the mRNA and protein levels of F9 in the liver tissue （P<0.01）. Medium- and high-dose YQWX upregulated the mRNA level of PLCD3 in the hippocampus and uterus （P<0.05， P<0.01）， as well as protein levels of CAMK2G and SNCAIP in the hippocampus （P<0.01）. ConclusionYQWX synergistically alleviates behavioral and neurobiochemical abnormalities in PMS rats by regulating key genes， providing a molecular basis for its traditional effects of replenishing Qi， nourishing blood， and harmonizing the liver and spleen.

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

OBJECTIVE: To explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.

Objective:To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma(MCL)cell line Jeko-1 and its related mechanism.Methods:The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs,respectively.CCK-8 assay was used to detect the proliferation of the cells,and Western blot was used to measure the protein expression levels of BCL-2,caspase-3,PI3K,AKT and P-AKT.Results:After Jeko-1 cells were treated with chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibrutinib(3.125,6.25,12.5,25,50 μmol/L)alone for 24,48,72h respectively,the cell proliferation was inhibited in a time-and dose-dependent manner.Moreover,the two drugs were applied in combination at low doses(single drug inhibition rate＜50％),and the results showed that the combination of two drugs had a more significant inhibitory effect(all P＜0.05).Compared with the control group,the apoptosis rate of the single drug group of chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibutinib(3.125,6.25,12.5,25,50 μmol/L)was increased in a dose-dependent manner.The combination of the two drugs at low concentrations(3.125,6.25,12.5 μmol/L)could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups(all P＜0.05).Compared with control group,the protein expression levels of caspase-3 in Jeko-l cells were upregulated,while the protein expression levels of BCL-2,PI3K,and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone.The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins,and the differences between the combination group and the single drug groups were statistically significant(all P＜0.05).Conclusion:Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1,and combined application of the two drugs shows a synergistic effect,the mechanism may be associated with the AKT-related signaling pathways.

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.

The study employed network Meta-analysis to evaluate the efficacy and safety of Chinese patent medicines combined with recombinant human interferon α-2b(interferon) in the treatment of cervical human papillomavirus(HPV) infections. The relevant randomized controlled trial(RCT) published from inception to May 8, 2024 were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science. The modified Jadad scale and the Cochrane risk of bias tool were used to evaluate the quality of the included studies, and RevMan 5.4, R 4.3.3, and Stata 17 were used for data analysis. A total of 105 RCTs were included, involving 12 732 participants and 7 Chinese patent medicines: Baofukang Suppository, Compound Seabuckthorn Seed Oil Suppository, Huangqi Shengmai Decoction, Kangfu Gel, Kangfuyan Capsules, Kushen Gel, and Puling Penyankang Granules. Network Meta-analysis yielded the following results:(1)For improving the negative conversion rate of HPV, SUCRA top-ranked intervention was Puling Penyankang Granules + interferon.(2) For shortening vaginal discharge time, SUCRA top-ranked intervention was Compound Seabuckthorn Seed Oil Suppository + interferon.(3) For reducing the serum level of hypersensitive C-reactive protein(hs-CRP), SUCRA top-ranked intervention was Baofukang Suppository + interferon.(4) For elevating the serum level of CD~+_4 T cells, SUCRA top-ranked intervention was Baofukang Suppository + interferon.(5) For elevating the serum level of CD~+_8 T cells, SUCRA top-ranked intervention was Kangfuyan Capsules + interferon.(6) For improving the CD~+_4/CD~+_8 ratio, SUCRA top-ranked intervention was Compound Seabuckthorn Seed Oil Suppository + interferon.(7)In terms of reducing serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), recurrence rate at 6 months after treatment, and incidence of adverse events, there were no significant differences between the interventions when compared pairwise. The cluster analysis revealed that Puling Penyankang Granules + interferon, Baofukang Suppository + interferon, Kangfu Gel + interferon, and Huangqi Shengmai Decoction + interferon simultaneously improved the negative conversion rate of HPV and reduced the incidence of adverse events. The findings suggested that Chinese patent medicines combined with interferon were effective in treating cervical HPV infection by enhancing the negative conversion rate, shortening the vaginal discharge time, and improving the levels of hs-CRP and T lymphocyte subsets. However, due to the limitations of sample size and quality of the included studies, these conclusions require further validation by studies with larger sample sizes and higher quality.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Papillomavirus Infections/virology* ; Interferon alpha-2/administration & dosage* ; Recombinant Proteins ; Drug Therapy, Combination ; Randomized Controlled Trials as Topic ; Antiviral Agents/administration & dosage* ; Interferon-alpha ; Papillomaviridae/physiology*