Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease (IBD). Huanglian Ganjiang decoction (HGD), derived from ancient book Beiji Qianjin Yao Fang, has demonstrated efficacy in treating UC patients traditionally. Previous research established that the compatibility of cold herb Coptidis Rhizoma + Phellodendri Chinensis Cortex (CP) and hot herb Angelicae Sinensis Radix + Zingiberis Rhizoma (AZ) in HGD synergistically improved colitis mice. This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice. The experimental colitis model was established by administering 3% dextran sulphate sodium (DSS) to mice for 7 days, followed by CP, AZ and CPAZ treatment for an additional 7 days. M1/M2 macrophage polarization levels, glucose metabolites levels and pyruvate dehydrogenase kinase 4 (PDK4) expression were analyzed using flow cytometry, Western blot, immunofluorescence and targeted glucose metabolomics. The findings indicated that CP inhibited M1 macrophage polarization, decreased inflammatory metabolites associated with tricarboxylic acid (TCA) cycle, and suppressed PDK4 expression and pyruvate dehydrogenase (PDH) (Ser-293) phosphorylation level. AZ enhanced M2 macrophage polarization, increased lactate axis metabolite lactate levels, and upregulated PDK4 expression and PDH (Ser-293) phosphorylation level. TCA cycle blocker AG-221 and adeno-associated virus (AAV)-PDK4 partially negated CP's inhibition of M1 macrophage polarization. Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate (DCA) partially reduced AZ's activation of M2 macrophage polarization. In conclusion, the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming. Specifically, CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition, while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.
Animals ; Drugs, Chinese Herbal/chemistry* ; Mice ; Macrophages/immunology* ; Glucose/metabolism* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics* ; Male ; Mice, Inbred C57BL ; Humans ; Colitis/drug therapy* ; Disease Models, Animal ; Colitis, Ulcerative/drug therapy* ; Metabolic Reprogramming

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10⁷/kg on day 0) and (4.0-6.8) ×10⁷/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.

OBJECTIVETo explore the factors associated with perinatal death of hepatic diseases in pregnancy (HDIP) and make feasible suggestions and measures for perinatal care of high risk patients.

METHODSThe 80 perinatal death cases of hepatic diseases in pregnancy (HDIP) during 1991-2000 in our hospital were analyzed retrospectively.

RESULTSThe perinatal mortality of HDIP in our hospital during the last 10 years was 17.99 approximately 65% was in utero death. Perinatal mortality was different between male (21.64%) and female (10.11%) (P<0.01). Compared first 5 years with last 5 years author found that the perinatal mortality of HDIP had no significant decrease (P>0.05). The perinatal mortality in city and suburbs had decreased, while in the floating population from other provinces the perinatal mortality had increased. The perinatal death was mainly caused by pregnancy induced hypertension (PIH) and asphyxia. But for the HBV carrier mothers the causes of death included umbilical cord problems, premature rupture of membrane and asphyxia.

CONCLUSIONSThe perinatal death mortality was increased by HDIP, deaths were essentially associated with pregnancy induced hypertension and asphyxia and the floating population and male gender were high risks. To enhance the management of HDIP or immigration, take effective therapies of hepatitis and improvement of resuscitation of newborns are critically important.

Adolescent ; Adult ; Cause of Death ; Female ; Fetal Death ; epidemiology ; Fetal Distress ; etiology ; mortality ; Humans ; Infant Mortality ; Infant, Newborn ; Liver Diseases ; complications ; mortality ; Male ; Pre-Eclampsia ; complications ; mortality ; Pregnancy ; Pregnancy Complications ; mortality ; Retrospective Studies ; Sex Factors

0 05). The positive rate of HbeAg (35 7%) in multiple group was significantly lower than in single group ( P 0 05) However, the incidences of premature rupture of membrane (PROM), premature delivery, 28 1%,25 0% fetal distress and newborn infant asphyxia 31 3%,25 0% in multiple hepatitis virus infection group were significantly higher than in single hepatitis virus infection group ( P