OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

The processing of traditional Chinese medicine(TCM) is a core theory within TCM, embodying deep philosophical, cultural, and natural scientific wisdom. Among the various techniques, the "synergistic processing of medicinal materials and excipients" has garnered significant attention due to its uniqueness. This study explored the impact of the adjuvant Glycyrrhizae Radix et Rhizoma on the dynamic process of component transformation during the processing of Aconiti Lateralis Radix Praeparata using techniques such as acidic dye colorimetry, UPLC-Q-TOF-MS/MS, density functional theory(DFT), and molecular dynamics simulations(MDS). The research revealed that during processing, various alkaloid components in Aconiti Lateralis Radix Praeparata exhibited different weak interactions with glycyrrhizic acid in Glycyrrhizae Radix et Rhizoma, affecting the transformation and content changes of alkaloid components such as aconitine, hypaconitine, and other diester-type alkaloids. This study, based on the dynamic process of "interactions between excipients and herbal medicine and component transformation", elucidated the intrinsic mechanism of processing of Aconiti Lateralis Radix Praeparata with Glycyrrhizae Radix et Rhizoma and provided a reference for understanding the scientific principles underlying the excipient processing of TCM.
Drugs, Chinese Herbal/chemistry* ; Aconitum/chemistry* ; Excipients/chemistry* ; Glycyrrhiza/chemistry* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Molecular Dynamics Simulation ; Alkaloids/chemistry* ; Glycyrrhizic Acid/chemistry*

OBJECTIVE: To investigate the mechanism of cytosolic phospholipase A2(cPLA2) inhibitor to improve neurological function after spinal cord injury (SCI). METHODS: Thirty-six 3 months old female SD rats, with body mass (280±20) g, were divided into three groups (n=12):sham group, SCI group, and SCI+ arachidonyl trifluoromethyl ketone(AACOCF3) group. Balloon compression SCI model was established in all three groups. In the sham model group, the spinal cord compression model was created after the balloon was placed without pressure treatment, and the remaining two groups were pressurized with the balloon for 48 h. After successful modeling, rats in the SCI+AACOCF3 group were injected intraperitoneally with AACOCF3, a specific inhibitor of cPLA2. The remaining two groups of rats were injected intraperitoneally with saline. The animals were sacrificed in batches on 7 and 14 days after modeling, respectively. And the damaged spinal cord tissues were sampled for pathomorphological observation, to detect the expression of cPLA2 and various autophagic fluxPrelated molecules and test the recovery of motor function. RESULTS: Spinal cord histomorphometry examination showed that the spinal cord tissue in the sham group was structurally intact, with normal numbers and morphology of neurons and glial cells. In the SCI group, spinal cord tissue fractures with large and prominent spinal cord cavities were seen. In the SCI+AACOCF3 group, the spinal cord tissue was more intact than in the SCI group, with more fused spinal cord cavities, more surviving neurons, and less glial cell hyperplasia. Western blot showed that the sham group had the lowest protein expression of LC3-Ⅱ, Beclin 1, p62, and cPLA2 compared with the SCI and SCI+AACOCF3 groups (P<0.05) and the highest protein expression of LC3-Ⅰ (P<0.05). P62 and cPLA2 expression in the SCI group were higher than in the SCI+AACOCF3 group (P<0.05). Behavioral observations showed that the time corresponding to BBB exercise scores was significantly lower in both the SCI and SCI+AACOCF3 groups than in the sham group (P<0.05). Scores at 3, 7, and 14 days after pressurization were higher in the SCI+AACOCF3 group than in the SCI group (P<0.05). CONCLUSION cPLA2 inhibitors can reduce neuronal damage secondary to SCI, promote neurological recovery and improve motor function by improving lysosomal membrane permeability and regulating autophagic flux.
Female ; Animals ; Rats ; Rats, Sprague-Dawley ; Neuroprotective Agents/pharmacology* ; Spinal Cord Injuries/drug therapy* ; Spinal Cord Compression

OBJECTIVE: To compare the effects of direct fluorescence in situ hybridization (D-FISH) detection without sorting and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) on cytogenetic analysis of patients with multiple myeloma (MM). METHODS: FISH test results of 229 patients with initial MM were retrospectively analyzed. The patients were divided into two groups, 140 patients were tested with D-FISH and 89 patients with MACS-FISH. The combination probe was designed as P53, D13S319, RB1, 1q21, and IgH. Cytogenetic detection results were compared between the two groups. RESULTS: The total detection rate of cytogenetic abnormalities in D-FISH group was 52.9%, and that in MACS-FISH group was 79.8%. There was a significant difference in the cytogenetic abnormality rate between the two groups (P=0.020). The abnormal genes with the highest detection rate in the two groups were 1q21 and IgH, respectively, while the lowest was P53. There was no significant difference in the percentage of P53 positive cells (positive rate) between the two groups, while D13S319, RB1, 1q21, and IgH showed significant difference in positive cell rate (P=0.0002, P<0.0001, P=0.0033, P=0.0032). There was no significant correlation between the proportion of plasma cells (PC) detected by bone marrow morphology and cytogenetic abnormality rate in the D-FISH group, while there was a correlation between the proportion of PC detected by flow cytometry and cytogenetic abnormality rate (r=0.364). The PC proportion detected by bone marrow morphology and flow cytometry in the MACS-FISH group had no correlation with the cytogenetic abnormality rate and positive cell rate of the 5 genes mentioned above. Additionally, the PC proportion detected by bone marrow morphology and flow cytometry showed significant difference (P<0.0001). CONCLUSION CD138 immunomagnetic bead sorting combined with FISH technology can significantly improve the abnormality detection rate of MM cytogenetics.
Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence/methods* ; Multiple Myeloma/genetics* ; Retrospective Studies ; Syndecan-1/immunology* ; Tumor Suppressor Protein p53/genetics*

Objective: To evaluate the immunogenicity of group A+C meningococcal polysaccharide conjugate vaccine in infants under 2 years old. Methods: From March 2017 to June 2018, 1 932 healthy infants in Biyang County, Henan Province, who were not vaccinated with meningococcal meningitis vaccine and whose axillary temperature was ≤37.0 ℃, were recruited as participants. The 3 months and 6-11 months old infants were allocated to the experiment group and the control group in a ratio of 1∶1. Infants aged 12-23 months were allocated to the 1-dose group, the 2-dose group and the control group in a ratio of 1∶1∶1, with 276 infants in each group. The infants in the experiment group were intramuscularly injected with freeze-dried group A+C meningococcal polysaccharide conjugate vaccine to be evaluated, and infants in the control group received intramuscular injection of commercially available freeze-dried group A+C meningococcal conjugate vaccine. The venous blood of infants was collected 30 days before the first dose and after the last dose of inoculation, and the antibody seroconversion of each group was determined and compared. Results: The completion rate of immunogenicity study was 95.2% (1 839/1 932). Before inoculation, there was no statistical difference in the geometric mean titer and positive rate of group A+C antibodies between the experiment group and the control group in 3 months and 6-11 months old infants (all P values >0.05). The geometric mean titers and positive rate of group A antibodies in the 1-dose group were higher than those in the control group (all P values <0.05), but there was no statistical difference between the 2-dose group and the control group (all P values >0.05) in infants aged 12-23 months. After inoculation, the differences (95%CI) in the positive conversion rate of group A+C antibodies between the experiment group and the control group were -0.12% (-6.01%-5.77%) and 0.82% (-4.23%-5.86%) in the 3 months old infants. At the age of 6-11 months, the differences were 6.75% (1.71%-11.79%) and -4.32% (-8.73%-0.08%), respectively. At the age of 12-23 months, the differences were 1.02% (-3.80%-5.83%) and -4.40% (-7.79%- -1.01%) in the 2-dose group and -7.22% (-12.90%- -1.54%) and -18.61% (-23.75%- -13.46%) in the 1-dose group, respectively. The geometric mean titers of group A+C antibodies in the 3 months old infants were 48.50 and 63.12, respectively, which had no significant difference from the control group (43.02 and 57.99, respectively) (both P values <0.05). The geometric mean titers of group A+C antibodies in the 6-11 months and 12-23 months old infants were 84.09 and 92.51 (2-dose group), which were higher than those in the corresponding control group (43.10 and 61.83, respectively) (all P values <0.001). Conclusion: Group A+C meningococcal conjugate vaccine has good immunogenicity in infants under 2 years old.
Humans ; Infant ; Child, Preschool ; Meningococcal Vaccines ; Vaccines, Conjugate ; Vaccination ; Neisseria meningitidis ; Polysaccharides ; Antibodies, Bacterial

Objective: To explore the clinical application and efficacy of lateral upper arm free flap (LUAFF) for one-stage repairing of soft tissue defect after oral cancer surgery. Methods: This article was a retrospective analysis of clinical data of 46 patients receiving treatment of one-stage repairing of soft tissue defect with LUAFF after oral cancer surgery in Hunan Cancer Hospital, from June 2019 to June 2021. Among these cases, 40 were males, and 6 were females. The patients' ages were from 23 to 64 years old. The clinical data of patients were reviewed and outcomes were evaluated. SPSS 23.0 software was used for statistical analysis. Results: In the LUAFF of 46 patients, flap area ranged from 5.0 cm×3.5 cm to 15.0 cm×7.0 cm; the mean pedicle length was 8.15±1.42 cm; the mean artery diameter was 1.20±0.41 mm (range, 1.5 to 2.5 mm); the mean diameter of the largest veins was 2.15±0.52 mm; and the median number of perforators was 2.6 (range, 1 to 4). All donor sites were closed primarily. Two cases had arterial anastomosis thrombosis, but their flaps were successfully saved with urgent re-anastomosis of the vessels. The overall flap survival rate was 93.5%(43/46), with flap necroses after operation in three cases. No patient received tracheotomy. The average hospital stay time of patients after operation was 9.4 days. The follow-up time was 6-24 months, elbow and wrist movements on the operative side were normal, and the upper limb muscle strength was not affected. Conclusions: LUAFF is a suitable choice for the repairs of small-moderate tissue defects in oral cancer surgery, with consistent perforators in the flap, simple harvest method, concealed donor-site scar, and high survival rate.
Female ; Male ; Humans ; Young Adult ; Adult ; Middle Aged ; Retrospective Studies ; Free Tissue Flaps ; Mouth Neoplasms ; Postoperative Period ; Cicatrix

Objective:To provide a scientific basis for the classification of Phyllanthi Fructus product grades. Method:A total of 30 batches of Phyllanthi Fructus currently available in the market were collected for quantification based on such appearance indexes as diameter， thickness， grain weight， and crust colour （L^*， a^*， and b^* values）. The contents of gallic acid， corilagin， chebulagic acid， and ellagic acid were measured by high performance liquid chromatography （HPLC）， followed by descriptive statistical analysis （DSA）， analysis of variance （ANOVA）， and principal component analysis （PCA） to determine the importance of each main index and explore the correlations between the appearance indexes and internal components. The classification standard of Phyllanthi Fructus product grades was formulated， and its scientificity was verified in hepatocelular carcinoma HepG2 cells. Result:The correlation analysis revealed that the crust colour L^*， a^*， and b^* values were significantly negatively correlated with corilagin， chebulagic acid， and ellagic acid （|r|>0.5， P<0.01）， but irrelevant to gallic acid （|r|<0.1）. Considering the variable coefficient of each index， PCA results， and the requirement of gallic acid as quality indicator for Phyllanthi Fructus in Chinese Pharmacopoeia， the crust colour L^*， a^*， and b^* values and gallic acid content were determined to be the classification indexes. The K-means cluster analysis confirmed that products with crust colour L^*<44， a^*<7， and b^*<10 and gallic acid content >1.6% could be classified into the first class， and those failing to meet the above requirements into the second class. The cell experiment demonstrated that the half-maximal inhibitory concentration （IC₅₀） of the first-class product against hepatocelular carcinoma HepG2 cells was lower than that of the second-class product. A colourimetric card was developed based on crust colour L^*， a^*， and b^* values to provide a visual tool for on-site evaluation of Phyllanthi Fructus products. Conclusion:This study has initially established the classification standard of Phyllanthi Fructus product grades， which contributes to guiding price negotiation of Phyllanthi Fructus products based on quality grade and thus ensuring high quality and high price.

To reveal the rationality of compatibility of Salviae Miltiorrhizae Radix et Rhizoma(SMRR) and Puerariae Lobatae Radix(PLR) from the perspective of pharmacokinetics, this study established a UPLC-MS/MS method for quantitative determination of PLR flavonoids(3'-hydroxy puerarin, puerarin, puerarin 6″-O-xyloside, 3'-methoxy puerarin, puerarin apioside) and salvianolic acids and tanshinones(salvianolic acid B, cryptotanshinone, and tanshinone Ⅱ_A) in plasma of rats. Rats were given SMRR extract, PLR extract, and SMRR-PLR extract by gavage and then plasma was collected at different time. UPLC separation was performed under the following conditions: Eclipse C_(18) column(2.1 mm×50 mm, 1.8 μm), 0.1% formic acid in water(A)-0.1% formic acid in acetonitrile(B) as mobile phase for gradient elution. Conditions for MS are as below: multiple reaction monitoring(MRM), ESI~(+/-). Comprehensive validation of the UPLC-MS/MS method(specifically, from the aspects of calibration curve, precision, accuracy, repeatability, stability, matrix effect, extract recovery) was performed and the result demonstrated that it complied with quantitative analysis requirements for biological samples. Compared with SMRR extract alone or PLR extract alone, SMRR-PLR extract significantly increased the AUC and C_(max) of PLR flavonoids and tanshinones in rat plasma, suggesting that the combination of SMRR and PLR promoted the absorption of the above components. The underlying mechanism needs to be further studied.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacokinetics* ; Plant Roots/chemistry* ; Pueraria/chemistry* ; Rats ; Rhizome/chemistry* ; Salvia miltiorrhiza/chemistry* ; Tandem Mass Spectrometry

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.
Child ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Malocclusion/prevention & control* ; Orthodontics, Interceptive