epsis is a systemic inflammatory response syndrome triggered by infection， and its high mortality rate is closely associated with immune imbalance， particularly the imbalance in the differentiation of helper T cell （Th） cell subsets [Th1， Th2， Th17， regulatory T cell （Treg） ] . In recent years， traditional Chinese medicine （TCM）， with its characteristics of multi-component and multi-target actions， has demonstrated unique advantages in regulating Th cell differentiation and function， as well as correcting immune imbalances in sepsis， offering new perspectives for immunotherapy of sepsis. This review summarizes relevant studies on the regulation of Th cell differentiation for sepsis treatment by TCM monomers and active ingredients （such as Astragalus membranaceus ， Scutellaria baicalensis ， Coptis chinensis ， Rheum palmatum ， Ganoderma lucidum ， Ginkgo biloba ， and Cistanche deserticola ）， the alcohol extract of Dai Baijie， and TCM formulas and preparations categorized as blood-activating and stasis-removing， purgative and laxative， warming and tonifying yang， and tonifying qi and nourishing yin. The results indicate that these TCM monomers， active ingredients， extracts， formulas， and preparations can regulate the Th1/Th2 and Th17/Treg balance， target the differentiation balance of Th cell subsets， alleviate inflammatory responses， or improve immune suppression， thereby exerting therapeutic effects on sepsis.

Sepsis-induced lung injury is a common type of sepsis complicated with multiple organ dysfunction syndrome， whose uncontrolled inflammatory response and oxidative stress are the key pathological mechanisms. As an important pathway of anti-inflammatory and anti-oxidative stress， the nuclear factor-erythroid 2-related factor 2 （Nrf2） signaling pathway is very important in the occurrence and development of sepsis-induced lung injury. This review summarizes relevant research conducted over the past decade on the regulation of the Nrf2 signaling pathway by traditional Chinese medicine （TCM） to ameliorate sepsis- induced lung injury. It has been found that 14 kinds of TCM effective ingredients （including five types of compounds： flavonoids， terpenes， alkaloids， saponins， phenols） and 6 kinds of compound preparations （including three types of formulas： heat-clearing and detoxifying formulas， purgative formulas for promoting bowel movement， and formulas for reinforcing vital qi and consolidating the constitution） can inhibit inflammatory responses and oxidative stress by activating Nrf2 signaling pathway and intervening in related pathways such as those involving Kelch-like ECH-associated protein 1， heme oxygenase-1， antioxidant response element and AMP-activated protein kinase， thereby alleviating sepsis-induced lung injury.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

BACKGROUND:Filamin B(FLNB)can crosslink the actin cytoskeleton into a dynamic structure that is essential for the directional movement of cells.It can regulate the proliferation,differentiation and apoptosis of chondrocytes.However,the effect of FLNB on osteoblast proliferation,migration and apoptosis has not been reported. OBJECTIVE:To investigate the effect of FLNB on the proliferation,migration and apoptosis of MC3T3-E1 cells. METHODS:The adenoviral vectors for knockdown of FLNB expression(sh-FLNB1,sh-FLNB2,sh-FLNB3)were constructed and infected with MC3T3-E1 cells.After screened by puromycin drug,the efficiency of FLNB knockdown was detected by western blot and RT-PCR.The MC3T3-E1 cell line with the best efficiency of FLNB knockdown was selected as the stable transient cell line of MC3T3-E1 for subsequent experiments.The cells were divided into blank group,mc3t3 group,sh-NC group(empty vector),and sh-FLNB group(sh-FLNB lentivirus).The blank group was cultured in cell-free α-MEM complete medium;the mc3t3 group was cultured in α-MEM complete medium alone;and the sh-NC and sh-FLNB groups were cultured with α-MEM medium containing 2.5 μg/mL puromycin.After 3 days of culture,cell counting kit-8 assay and cell scratch assay were used to detect the proliferation and migration ability of MC3T3-E1;flow cytometry was used to detect cell apoptosis;and RT-PCR was used to detect the expression of apoptosis-related genes. RESULTS AND CONCLUSION:Western blot and RT-PCR results showed that the efficiency of FLNB knockdown was the best in the sh-FLNB3(P<0.000 1),which was used as a stable cell line for subsequent experiments.Cell counting kit-8 data showed that the proliferative ability of MC3T3 cells was significantly weakened after knockdown of FLNB(P<0.05).Cell scratch assay results showed that the migration ability of MC3T3 cells was significantly decreased after knockdown of FLNB.Flow cytometry and RT-PCR results showed that the apoptotic rate of MC3T3-E1 cells increased after knockdown of FLNB,the expression of pro-apoptotic factor Bax increased significantly,and the expression of anti-apoptotic factor Bcl-2 decreased significantly(P<0.05).To conclude,knockdown of FLNB can reduce the proliferation ability of MC3T3-E1 cells,decrease the migration ability of the cells,and increase cell apoptosis.

Objective: To investigate the intake of liquid dairy products and identify its influencing factors among the fourth grade students in Nanjing City. Methods: The fourth grade students were selected as the study subjects in Nanjing City using a multi-stage random cluster sampling method in September 2020. Their general information, frequency of liquid dairy product intake one week prior to survey and mean intake amount per time were collected. According to the 2016 Dietary Guidelines for Chinese Residents, weekly intake of liquid dairy products of 2 100 g and greater was defined eligible. Factors affecting the frequency and amount of liquid dairy product intake were identified using multivariable logistic regression analysis. Results: A total of 2 268 questionnaires were allocated and 2 216 valid questionnaires were recovered, with an effective recovery rate of 97.71%. The respondents included 1 199 boys ( 54.11% ) and 1 017 girls ( 45.89% ). The frequency of liquid dairy product intake was (6.41±4.86) times per week, and the median intake amount was 1 250.00 g per week (interquartile range, 1 750.00 g per week). There were 607 students ( 27.39% ) consuming liquid dairy products of 2 100 g and greater a week, and 1 016 students ( 45.85% ) consumed liquid dairy products for 7 times and more a week. Multivariable logistic regression analysis showed that living in urban areas ( OR=1.204, 95%CI: 1.005-1.443 ), knowing nutrition labels ( OR=1.221, 95%CI: 1.021-1.460 ), periodical measurement of body weight (OR=1.486, 95%CI: 1.098-2.011) and restricted intake of sugar-containing drinks ( OR=1.264, 95%CI: 1.005-1.590 ) facilitated the intake of liquid dairy products for 7 times and more a week, and students with periodical measurement of body weight were more likely to consume liquid dairy products for 2 100 g and greater a week ( OR=1.821, 95%CI: 1.240-2.676 ). Conclusions Inadequate intake of liquid dairy products is found among the fourth grade students in Nanjing City. Residence, awareness of nutrition labels, periodical measurement of body weight, and parental restriction of sugar-containing drink intake affect the intake of liquid dairy products.

Objective To explore the effects of Kangshuaiyizhi capsule on ChAT/AchE and NE, DA and 5-HT levels in the brain tissue of aging model rats, and explore its effect of protecting cerebral function. Methods Totally 72 rats were randomly divided into normal group and model group. The subacutely aging model rats were made by injecting D-gal (0.125 g/kg) into abdominal cavity continually, then aging rats were divided by random number table into model group, Naofukang group and Kangshuaiyizhi high-, low-dose group. After intervented with correspongding drugs for 60 days, activity of ChAT and AchE, cerebral cortex NE, DA, and 5-HT levels were detected. Results Activity of AchE was much higher (P<0.05), but level of ChAT, NE, DA and 5-HT in model group were significantly downregulated compared with normal group (P<0.05). After treated with Kangshuaiyizhi capsule, activity of AchE was downregulated, ChAT, NE, DA and 5-HT levels were significantly upregulated (P <0.01, P <0.05). Conclusion Kangshuaiyizhi capsule can regulate cholinergic and monoamine neurotransmitter levels in the brain tissue of aging model rats, and play a very important role in protecting cerebral function.

Objective To investigate the anti-inflammatory/immune modulatory effects of high-expressing membrane bound M-CSF-hematopoietic malignant cells on macrophages. Methods After coculturing RAW264.7 and murine macrophage cell line with Namalwa-M, a cell line stably expressing mM-CSF, and companing with Nainalwa-V, a cell line stably transfected with the empty vector as the control, flow cytometry was used to detect the expression of the marker of alternatively activated macrophages, CD206, and intracellular expression of IL-10, IL-12, IL-6 and TNF-α to study the immunophenotype of RAW264.7; phagocytic assays to investigate their functional activity in vitro. Results RAW264.7 cocultured with Namalwa-M consistently showed high-level expression of CD206, which indicated activities of these macrophage cells were increased. Furthermore, these RAW264.7 expressing high levels of IL-10, TNF-a and low levels of IL-12, IL-6, as determined by intracellular staining were suggested that the phagocytic activity was increased. Functionally, RAW264.7 cocultured with Namalwa-M showed a higher level of phagocytic activity. Conclusion Macrophage generated in vitro after cocultured with mM-CSF-expressing hematopoietic malignant cell line could be transformed into abnormal macrophage with an immunophenotype defined as IL-10-high, IL-12-low, IL-6-low and TNF-α-high.

Objective To evaluate family economic burden of children with autism, or with physical disability or with intellectual disability.Methods227 parents of children with autism, children with physical disability, children with intellectual disability and normal children were interviewed for their family economic burden.ResultsThe medical cost and caring cost of children with disability were significantly more than those of normal children, and the education cost, clothes cost and amusement cost of children with disability were significantly less than those of normal children. Family income was only affected by education level of parents. Families of children with disability received more economic assistance than families of normal children except families of autistic children. More children the family had, less economic assistance the family acquired. Compared with normal children, the family economic burden of children with disability were as following, children with autism (19582.4 RMB per year), children with physical disability (16410.1 RMB per year), children with intellectual disability (6391.0 RMB per year). ConclusionFamilies of children with autism, children with physical disability and children with intellectual disability had heavier economic burden than families of normal children.

OBJECTIVETo understand the clinical feature and natural course of polycythemia vera (PV).

METHODSThe clinical symptoms, signs, laboratory examination and prognosis of 185 patients with PV were analysed.

RESULTSThere are 122 males and 63 females. The mean age was (52.7 +/- 14.1) years. The mean hemoglobin level was (208.3 +/- 21.2) g/L. Pancytosis was displayed in 74 (40%) cases, excess of red blood cells in 33 (17.8%), excess of red blood cells and granulocytes in 67 (36.2%) and excess of red blood cell and platelets in 11 (5.9%). Splenomegaly was found in 123 (66.5%) patients and hepatomegaly in 30 (16.2%). Quantitative assess of serum Epo was done in 25 patients. The level was low in 16 (64.2%) and normal in 9 (36.0%). Hematopoietic progenitor culture yields was elevated in 11 patients, endogenous erythroid colonies (EEC) formation was found in 10 cases (90.9%). Eighty two patients (44.3%) had 101 attacks of vascular thrombotic incidents, 7 patients developed myelofibrosis (MF). Secondary cancer occurred in 1 patient. Two patients died of thrombosis.

CONCLUSIONPV is an elderly adult myeloproliferative disease with a high frequency of thrombosis. EEC can be found out in PV patients. The serum Epo level is not increased in PV patients. The main sequelae of PV is MF.

Adult ; Aged ; Erythrocyte Count ; Female ; Hemoglobins ; metabolism ; Hepatomegaly ; etiology ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Polycythemia Vera ; blood ; complications ; pathology ; Primary Myelofibrosis ; etiology ; Splenomegaly ; etiology ; Thrombosis ; etiology

OBJECTIVETo detect the quantity, proportion and function of producing cytokines of Th1 and Th2 cells in aplastic anemia (AA) patients and their contribution to the hematopoietic failure.

METHODS(1) Eleven patients with severe aplastic anemia (SAA) at diagnosis were observed by Marsh's method for the CFU-E, BFU-E and CFU-GM before and after depletion of CD(4)(+) T lymphocytes from bone marrow mononuclear cells (BMMNC); (2) Th1 (CD(4)(+) IFN-gamma(+)) and Th2 (CD(4)(+) IL-4(+)) cells in peripheral blood mononuclear cells (PBMNC) of 21 SAA patients and 17 normal controls were counted by FACS. (3) mRNA expression of IFN-gamma and IL-4 gene in unstimulated BMMNC from 16 SAA patients, 11 chronic aplastic anemia (CAA) patients, 26 other hematological diseases patients and 11 normal controls were measured by reverse transcriptase polymerase chain reaction (RT-PCR).

RESULT(1) CFU-E, CFU-GM and BFU-E increased significantly after depletion of CD(4)(+) T lymphocytes from BMMNC of SAA patients. (2) The percentage of IFN-gamma producing CD(4)(+) T cell (Th1) of SAA patients was significantly higher than that of controls, the percentages of IL-4 producing CD(4)(+) T cells (Th2) had no difference between SAA patients and normal controls. (3) IFN-gamma mRNA was detected in unstimulated BMMNC in 13 of 16 SAA patients, 6 of 11 CAA patients and one of 6 paroxysmal nocturnal hemoglobinuria (PNH) patients. The IFN-gamma mRNA was not detected in unstimulated BMMNC of 11 normal controls and other hematological diseases patients.

CONCLUSIONSDisbalance of CD(4)(+) T lymphocytes subsets and increases in quantity and IFN-gamma producing function of Th1 cells might be important for the development of bone marrow failure in AA and in distinguishing AA from other kinds of pancytopenic diseases.

Adolescent ; Adult ; Anemia, Aplastic ; blood ; etiology ; Colony-Forming Units Assay ; Erythroid Precursor Cells ; cytology ; Female ; Granulocytes ; cytology ; Hematopoietic Stem Cells ; cytology ; Humans ; Interferon-gamma ; genetics ; Interleukin-4 ; genetics ; Macrophages ; cytology ; Male ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Th1 Cells ; cytology ; metabolism ; physiology ; Th2 Cells ; cytology ; metabolism