Objective: To identify the phenotypes, antibodies and explore the molecular mechanisms of a patient who carries antibodies to RBC high-frequency antigens and his family members. Methods: The antibody identification test was performed for the proband by serological methods, and targeted NGS was subsequently used to detect mutations that occurred in blood group genes. Blood samples were collected from the proband and his family members. Sanger sequencing was used to verify the mutation of the XK gene. The expression of Kell blood group antigens was detected by serological methods and flow cytometry. K cells were used to detect the antibody specificity of the proband. The morphology of red blood cells was detected by the scanning electron microscopy. The serum creatine kinase levels of the proband and his family members were analyzed by colorimetric methods. Results: The results of the antibody identification test suggested that the proband might have antibodies to high-frequency antigens. NGS results suggested a homozygous mutation (c. 107G>A) in exon 1 of the XK gene in the proband, resulting in a truncated XK protein. The Sanger sequencing results of the proband were consistent with the NGS results, and the mutation was not found in other family members. The expression of Kell blood group antigens of the proband was not found by serological methods and flow cytometry. The results of the antibody specificity test showed that the proband had anti-Km antibodies. Spike-like changes were identified on red blood cells, and serum creatine kinase level was elevated in the proband. Conclusion: In this study, the McLeod phenotype caused by homozygous mutation (c. 107G>A) of XK gene was identified in Chinese individuals for the first time by the phenotype and molecular mechanism studies. The results of genotyping and phenotyping suggested that the McLeod phenotype caused by the mutation was compatible with the phenotypes of McLeod and K .

Nuclear factor-kappa B （NF-κB） is an important intracellular transcription factor widely involved in the processes such as immune response， inflammatory response， cell proliferation， and apoptosis. The abnormal activation of the NF-κB signaling pathway plays a pivotal role in various liver diseases including chronic hepatitis， liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. Extensive studies have shown that inhibiting NF-κB activity may effectively reduce inflammation and fibrosis and improve metabolic disorders. Several natural compounds， such as matrine and salvianolic acid B， have shown the potential in suppressing NF-κB activity， thereby exerting anti-inflammatory， anti-fibrotic， and anti-tumor effects. This article systematically reviews the critical role of the NF-κB signaling pathway in liver diseases and its potential as a therapeutic target， in order to highlight its potential as a therapeutic target for liver diseases and provide new directions for the treatment of liver diseases.

Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.

Objective:To explore the mechanism of herb-partitioned moxibustion in relieving rat intestinal inflammation by focusing on the neutrophil extracellular traps(NETs)in Crohn disease(CD)development. Methods:Rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion group,and a mesalazine group.The CD rat model was prepared with 2,4,6-trinitrobenzene sulfonic acid except for rats in the normal group.Rats in the normal group and model group did not receive any treatment but had the same fixation as the other groups.Rats in the herb-partitioned moxibustion group received herb-partitioned moxibustion at Qihai(CV6)and bilateral Tianshu(ST25).Rats in the mesalazine group received intragastric administration of mesalazine enteric-coated tablets.The general situation of rats in each group was recorded,and the histopathological changes in the colon were observed and scored by hematoxylin-eosin staining.The serum concentrations of NETs DNA(NETs-DNA),neutrophil elastase(NE)-DNA,and myeloperoxidase(MPO)-DNA were detected by ABC enzyme-linked immunosorbent assay,and the citrullinated histone 3(citH3),MPO,and NE protein and mRNA expression levels in rat colon tissue were observed by immunofluorescence and real-time quantitative polymerase chain reaction. Results:Compared with the normal group,the mucosal ulcer reached the muscularis,the epithelium was incomplete,the goblet cells decreased obviously with significant inflammatory cell infiltration in the colon;the colonic mucosa damage index(CMDI)score increased significantly(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations increased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue increased significantly in the model group(P<0.01 or P<0.05).Compared with the model group,the mucosal epithelium in the herb-partitioned moxibustion group and the mesalazine group was repaired and the goblet cells increased with a few infiltrating inflammatory cells in the colon;the CMDI score decreased(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations decreased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue was down-regulated(P<0.01 or P<0.05). Conclusion:Herb-partitioned moxibustion reduced the serum NETs complex and inhibited the protein and mRNA expression of NETs complex in the colon tissue,which may be one mechanism of herb-partitioned moxibustion in relieving colon mucosal inflammation in CD.

Objective: To observe the clinical efficacy of herbal cake-partitioned moxibustion for ulcerative colitis (UC) and elucidate its mechanism by targeting the vitamin D receptor (VDR) signaling pathway. Methods: A total of 63 patients with UC were randomly divided into an observation group (30 cases, treated with herbal cake-partitioned moxibustion) and a control group (33 cases, treated with sham herbal cake-partitioned moxibustion). Moxibustion treatment was performed at Qihai (CV6) and bilateral Tianshu (ST25) and Shangjuxu (ST37), 3 times per week for 12 weeks. The total effective rate, visual analog scale (VAS) score for abdominal bloating and pain, and hospital anxiety and depression scale (HADS) score were compared between the two groups. Enzyme-linked immunosorbent assay was used to detect the concentrations of serum C-reactive protein (CRP), 25-hydroxyvitamin D [25(OH)D], and interleukin-12 (IL-12)/interleukin-23 (IL-23) p40. Immunohistochemistry was used to observe the expression levels of VDR and regenerating gene Ⅳ (Reg Ⅳ) proteins in colonic mucosa. The expression levels of VDR, cytochrome p45027B1 (CYP27B1), and Reg Ⅳ mRNAs were detected by real-time fluorescence quantitive polymerase chain reaction. Results: After treatment, the total effective rate in the observation group was 86.7％, which was significantly higher than 51.5％ in the control group (P<0.05). After treatment, the VAS scores for abdominal bloating and pain in the observation group were significantly decreased (P<0.01), as well as the HADS-depression subscale (HADS-D) and HADS-anxiety subscale (HADS) scores (P<0.05), while only the VAS score for abdominal pain in the control group was reduced (P<0.05), and the improvements of the scores in the observation group were more significant than those in the control group (P<0.05). After treatment, the serum CRP concentrations in both groups and the IL-12/IL-23 p40 concentration in the observation group were significantly decreased (P<0.05), and the concentrations in the observation group were lower than those in the control group (P<0.05). The expression levels of VDR protein and mRNA in the colon in both groups were all increased (P<0.01), and the expression levels of Reg Ⅳ protein and mRNA and CYP27B1 mRNA were all decreased in the two groups (P<0.05 or P<0.01); the improvements in the observation group were more notable than those in the control group (P<0.05 or P<0.01). Conclusion: Herbal cake-partitioned moxibustion can effectively alleviate abdominal pain and diarrhea in patients with UC, improve depression and anxiety disorders, and regulate the expression of related proteins in the VDR signaling pathway. The mechanism may be related to inhibiting intestinal inflammation by reducing the release of the proinflammatory cytokine IL-12/IL-23 p40.

Objective:To systematically assess the efficacy and safety of acupuncture therapy for essential hypertension.Methods:A computerized literature search of the Chinese National Knowledge Infrastructure(CNKI),Chongqing VIP Database(CQVIP),Wanfang Academic Journal Full-text Database(Wanfang),China Biology Medicine Disc(CBM),PubMed,Excerpta Medica Database(EMBASE),and Cochrane Library was conducted to retrieve randomized controlled clinical trials on acupuncture as the main intervention for the treatment of essential hypertension published from the inception of the database to 30 January 2021.The risk-of-bias assessment was carried out for each included study according to the Cochrane Handbook.Data analysis was performed using Review Manager 5.4.1 and Stata 15.0.Results:After the screening,46 randomized controlled trials involving a total of 3 859 subjects were included.Primary outcomes included changes in the diastolic blood pressure after intervention[eight studies showed that the acupuncture plus antihypertensive drug group was better than the antihypertensive drug monotherapy group[mean difference(MD)=1.45,95%confidence interval(CI)(0.48,2.43),P=0.004,fixed effects model;I2=39%]and changes in the systolic blood pressure after intervention{11 studies showed that the acupuncture plus antihypertensive drug group was better than the antihypertensive drug monotherapy group[MD=8.60,95%CI(7.12,10.07),P<0.00001,fixed effects model;I2=26%]}.The secondary outcome was antihypertensive efficacy,12 studies of acupuncture monotherapy group[risk ratio(RR)=1.20,95%CI(1.12,1.28),P<0.00001,fixed effects model;I2=36%]and 15 studies of acupuncture combined with antihypertensive drug group[RR=1.27,95%CI(1.20,1.34),P<0.00001,fixed effects model;I2=6%]showed better results than the antihypertensive drug monotherapy group in antihypertensive efficacy.In terms of the adverse events,four studies showed that the acupuncture monotherapy group had fewer adverse events than the antihypertensive drug monotherapy group[RR=0.10,95%CI(0.04,0.25),P<0.00001,fixed effects model;I2=0%].Conclusion:Acupuncture combined with antihypertensive drugs is superior to antihypertensive drugs alone in reducing blood pressure,and acupuncture therapy is effective and safe for the treatment of essential hypertension with fewer side effects.However,there is still a lack of high-quality multicenter randomized double-blinded controlled trials in this field.Rigorous large-sample clinical trials are needed to validate these findings.

Objective:To explore the mechanism of acupuncture and moxibustion for ulcerative colitis(UC)from the perspective of the P2X7 receptor(P2X7R)-nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome pathway. Methods:Sprague-Dawley rats were randomly assigned to a normal(N)group,a model(M)group,a herb-partitioned moxibustion(HM)group,and an electroacupuncture(EA)group.For modeling,the rats drank 4%dextran sulfate sodium for 7 d.Rats in the HM group and EA group received 7 consecutive days of HM or EA at bilateral Tianshu(ST25),respectively.The histopathological change in colon tissue was observed by hematoxylin-eosin(HE)staining;immunofluorescence staining was used to detect the protein expression of related molecules in the colon tissue,and enzyme-linked immunosorbent assay was used to detect the concentrations or contents of related molecules in the serum and colon tissue.Wild-type(WT)and P2X7R gene knockout(KO)mice were used to construct UC models,histopathological changes in the colon tissue were observed by HE staining,and the NLRP3 protein expression in the colon tissue was observed by immunohistochemistry. Results:Compared with the N group,the colon histopathological score in the M group was significantly increased,and the protein expression of P2X7R,NLRP3,apoptosis-associated speck-like protein containing CARD(ASC),Caspase-1,interleukin-1β(IL-1β),and interleukin-18(IL-18)in the colon tissue and the protein levels of IL-1β and IL-18 in the serum were significantly increased(P<0.05).Compared with the M group,the histopathological scores of the colon in the HM group and the EA group were significantly decreased,and the protein expression levels of P2X7R,NLRP3,ASC,Caspase-1,IL-1β,and IL-18 in the colon tissue and the protein level of IL-18 in the serum were significantly decreased(P<0.05).After UC modeling,the colonic mucosal epithelial damage and inflammatory cell infiltration in P2X7R KO mice were less than those in WT mice,and the NLRP3 protein expression in the colon was also decreased compared with that in WT mice(P<0.05). Conclusion:HM and EA at Tianshu(ST25)may inhibit the protein activities of P2X7R,NLRP3,ASC,and Caspase-1 in the colon tissue of rats with UC,thereby reducing the downstream molecules IL-1β and IL-18 in the P2X7R-NLRP3 inflammasome pathway to relieve UC inflammation.

Objective: To observe the effect of moxibustion on the colonic mucosal barrier of rats with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS). Methods: Forty male Sprague-Dawley rats were randomly divided into a normal group and a modeling group, with 20 rats in each group. Rats in the modeling group were subjected to preparing experimental UC models by drinking 4％ DSS for seven consecutive days. Two modeled rats and two normal rats were randomly selected for model identification. After the success of UC model was confirmed, the remaining 18 modeled rats were randomly divided into three groups, a model group, a model + herbal cake-partitioned moxibustion group, and a model + mild moxibustion group, with six rats in each group; the remaining normal rats were randomly divided into three groups, a normal group, a normal + herbal cake-partitioned moxibustion group, and a normal + mild moxibustion group, with six rats in each group. After 7 d of intervention with the herbal cake-partitioned moxibustion or the mild moxibustion, hematoxylin-eosin (HE) staining technique was used to observe the pathological changes of colon tissue under a light microscope; Western blotting and/or immunohistochemical techniques were used to detect the protein expression levels of Occludin, Claudin, junction adhesion molecular 1 (JAM1), mucin 2 (MUC2), and transforming growth factor beta1 (TGF-β1) in rat colon tissue. Results: Compared with the normal group, the colon tissue was severely damaged, the pathological score was significantly increased, and the protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 were significantly decreased in the model group (P<0.01); while there were no significant differences in the colonic histopathological score, protein expression levels of Occludin, Claudin, JAM1, MUC2, and TGF-β1 in the normal + herbal cake-partitioned moxibustion group and the normal + mild moxibustion group (P>0.05). Compared with the model group, the model + herbal cake-partitioned moxibustion group and the model + mild moxibustion group showed repaired colon tissue, ulcer healing, significantly reduced pathological score, and significantly increased protein expression levels of JAM1, MUC2, and TGF-β1 (P<0.05); the Occludin protein expression level in the colon tissue of the model + mild moxibustion group was increased (P<0.01). Conclusion: Neither herbal cake-partitioned moxibustion nor mild moxibustion influences the colonic histopathology and intestinal mucosal barrier-related protein expression in the normal rats; both herbal cake-partitioned moxibustion and mild moxibustion can up-regulate the protein expression levels of JAM1, MUC2, and TGF-β1 in the colon tissue of UC rats. Mild moxibustion can up-regulate Occludin protein expression. This may be a mechanism of moxibustion in reducing colonic mucosa inflammation in UC.

Objective: To explore the correlation between the parameters of the mandible and parameters of cervical vertebrae and craniofacial bone in class Ⅱ skeletal patients in Northeast China and to establish correlation equations expressing the relationship between the mandible and cervical vertebrae and craniofacial bone directly and quantitatively for the clinical diagnosis and treatment of orthodontics and orthognathics and for prediction. Methods : The mandible, cranial facial bone and cervical vertebrae of 201 children and adolescents aged 8 to 20 years were measured using digital cranial lateral tablets. All of the cases were divided into male (n=75) and female (n=126) groups using a sensitivity analysis method based on genetic algorithms to select the craniofacial bone and cervical bone with strong sensitivity to mandible parameters and to establish relevant equations. Results : Through sensitivity analysis, the parameters with the strongest correlation between the measured values of the mandible were H4 and SN, those with a strong correlation were SN-Ar, the anterior and posterior high ratio SGo/NGn, the Y axis angle and mandibular angle Ar-Go-Gn. The established equation was as follows: males: Ar-Pg=28.415+1.818×H4+0.746×SN(r2=0.056 8, P < 0.001); females: Ar-Pg=15.168+1.706×H4+0.675×SN+0.31×SN-Ar-0.29×Y axis angle (r2=0.611, P < 0.001). No significant difference was found between the predicted values obtained by the established equations and measured values (P > 0.05). Conclusion The mandibular length equation established by sensitivity analysis and genetic algorithms is statistically significant and can predict a certain degree of growth and development.

Objective To investigate the dosimetric differences among three types of breath hold mode ( free breath:FB, thoracic deep inspiration breath hold: T-DIBH, abdomen deep inspiration breath hold:A-DIBH) and to explore the optimal breath hold method in the postoperative radiotherapy of left-side breast cancer patients with minimum dose to normal tissues and organs at risk. Methods A total of eighteen patients with left-side breast cancer patients who underwent postoperative radiotherapy were enrolled in this study. Three CT simulation scans with three different breath hold method ( FB, T-DIBH, and A-DIBH ) were performed for each patient. Dosimetric differences were compared among plans generated on these three different CT image sets. Results There was no significant difference in the volume, mean dose, and homogeneity of planning target volume ( PTV) among plans generated from three different image sets (P>0. 05). The mean heart dose, mean LAD dose and mean ipsilateral lung dose in plans generated from CT image sets with FB, T-DIBH and A-DIBH were (3. 21 ± 1. 02), (1. 74 ± 0. 51), (1. 31 ±0. 41) Gy (W =171, P <0. 05), (34. 61 ± 13. 51), (14. 38 ±10. 20), (9. 21 ± 6. 53) Gy (W=171, P<0. 05), and (8. 31 ±2. 75), (7. 46 ±1. 96), (6. 89 ±1. 79) Gy (W=171, P<0. 05), respectively. Conclusions Compared with plans with FB, plans with DIBH ( T-DIBH and A-DIBH ) achieved lower cardiac, LAD and pulmonary doses. A-DIBH achieved a better normal dose reduction than T-DIBH.