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 .

Polyunsaturated fatty acids (PUFAs) have diverse health-promoting effects, such as potentially protecting in immune, nervous, and cardiovascular systems by targeting a variety of sites, including most ion channels. Voltage-gated potassium channels of the K_V7 family and large-conductance Ca²⁺- and voltage-activated K⁺ (BK_Ca) channels are expressed in many tissues, therefore, their physiological importance is evident from the various disorders linked to dysfunctional K_V7 channels and BK_Ca channels. Thus, it is extremely important to learn how potassium channels are regulated by PUFAs. The aim of this review is to provide an overview of the effects of PUFAs on K_V7 channels and BK_Ca channels functions, as well as the mechanisms underlying these effects. In summarizing reported effects of PUFAs on K_V7 and BK_Ca channels mediated currents, we generally conclude that PUFAs increase the current amplitude, meanwhile, differential molecular and biophysical mechanisms are associated with the current increase. In K_V7 channels the currents increasement are associated with a shift in the voltage dependence of channel opening and increased maximum conductance in K_V7 channels, while in BK_Ca channels, they are associated with destabilization the pore domain closed conformation. Furthermore, PUFA effects are influenced by auxiliary subunits of K_V7 and BK_Ca channels, associate with channels in certain tissues. although findings are conflicting. A better understanding of how PUFAs regulate K_V7 and BK_Ca channels may offer insight into their physiological regulation and may lead to new therapeutic strategies and approaches.

Neck dissection(ND)is one of the main treatment methods for oral and maxillofacial malignancies.Although ND type is in con-stant improvement,but intraoperative peal-pull-push injury of the accessory nerve,muscle,muscle membrane,fascia and ligament induced shoulder syndrome(SS)is still a common postoperative complication,combined with the influence of radiochemotherapy,not only can cause pain,stiffness,numbness,limited dysfunction of shoulder neck and arm,but also may have serious impact on patient's life quality and phys-ical and mental health.At present,there is still a lack of a systematic evaluation and rehabilitation management program for postoperative SS of oral and maxillofacial malignant tumors.Based on the previous clinical practice and the current available evidence,refer to the relevant lit-erature at home and abroad,the experts in the field of maxillofacial tumor surgery and rehabilitation were invited to discuss,modify and reach a consenusus on the etiology,assessment diagnosis,differential diagnosis,rehabilitation strategy and prevention of SS,in order to provide clinical reference.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To construct and validate a risk-scoring model for predicting delayed onset of lactogenesis stage Ⅱ (DOL Ⅱ) in mothers separated from their premature infants.Methods:This was a retrospective study. (1) Modeling group: This group enrolled 310 mothers who were separated from their premature infants after delivery at Wuxi Maternal and Child Health Hospital from December 2021 to November 2022. They were further divided into the DOL Ⅱ group (144 cases) and the non-DOL Ⅱgroup (166 cases) according to whether they had DOL Ⅱ or not. Based on the results of multivariate logistic regression analysis, each risk factor was assigned a score, and a risk prediction scoring model was established. (2) Validation group: This group included 130 mothers of premature infants who experienced mother-infant separation after delivery at Wuxi Maternal and Child Health Hospital from December 2022 to March 2023. The area under the receiver operating characteristic (ROC) curve was used to evaluate the discrimination, and the Hosmer-Lemeshow test was used to assess the goodness of fit. The Chi-square test (or Fisher's exact probability test) or Wilcoxon rank sum test were used for inter-group data comparison. Results:This risk prediction scoring model included 10 risk factors [maternal age≥35 years old, hypertensive disorders of pregnancy, anemia, gestational diabetes mellitus, preterm rupture of membrane, start breastfeeding >6 hours, postpartum admission of maternal intensive care unit, cesarean section, score of Edinburgh Postpartum Depression Scale >9.5, postpartum neutrophil-to-lymphocyte ratio ≥4.369, Fatigue Scale-14 ≥7.5, body mass index in the first trimester ≥23.719 kg/m 2, postpartum BMI≥27.661 kg/m 2,and increase of BMI during pregnancy ≥5.393 kg/m 2], with an area under the ROC curve of 0.838 (95% CI: 0.795-0.882, P<0.001), a maximum Yoden index of 0.526, a specificity of 0.825, a sensitivity of 0.701, and an optimal threshold of 4.5. After rounding the score off to the nearest whole number, those with a score≥5 were defined as at high risk of DOL Ⅱ, while those with a score<5 were at low risk. Hosmer-Lemeshow test showed χ2=3.43 and P=0.634. The positive predictive value, the negative predictive value, and the accuracy were 77.7%, 76.1%, and 76.8%, respectively. In the modeling group, 130 out of the 310 cases (41.9%) were predicted to be at high risk by the model with 101 (32.6%) experiencing DOL Ⅱ, while 180 cases (58.1%) were predicted to be at low risk with 43 (13.9%) experiencing DOL Ⅱ. Among the 130 cases in the validation group, 59 (45.4%) were predicted to be at high risk with 39 (30.0%) experiencing DOL Ⅱ, while 71 (54.6%) were predicted to be at low risk with 19 (14.6%) experiencing DOL Ⅱ. The model validation results showed that the area under the ROC curve was 0.774 (95% CI: 0.693-0.855, P<0.001) and the Hosmer-Lemeshow test showed χ2=3.09 and P=0.687, with the positive predictive value of 66.1%, the negative predictive value of 73.2%, and the accuracy of 70.0%. Conclusions:This study preliminarily establishes a risk scoring model for predicting DOL Ⅱ in mothers separated from their premature infants which is of certain predictive value and can provide a reference for developing predictive lactation support measures.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Based on the octahedral modifiable structures and kinetic inertness, platinum (IV) complexes have become antitumor prodrug candidates to mitigate platinum (II) drug resistance and side effects. The nitrobenzoxadiazole derivative (NBDHEX) can inhibit the activity of glutathione S-transferases (GSTs) and be introduced to conjugate with platinum(II) complexes DN603 and DN604 to yield two platinum (IV) complexes DN603/DN604-NBD. In vitro assays demonstrated that DN603/DN604-NBD could significantly inhibit the proliferation of cisplatin-sensitive A549 and resistant A549/cDDP cancer cells. The uptake of DN603/DN604-NBD in A549/cDDP cells was much higher than that of cisplatin, causing a higher rate of cell apoptosis and a greater ratio of Bax/Bcl-2, the activation of caspase-3 and cleavage of DNA repair enzyme (PARP), inducing the mitochondria-dependent cell apoptosis pathway. DN603/DN604-NBD could induce higher reactive oxygen species (ROS) levels, significantly enhance phosphorylation of histone H2AX on Ser-139 (γ-H2AX) fluorescence intensity and cause a greater degree of DNA double-stranded damage. Studies have shown that GSTs kinase GSTP1 was highly expressed in cisplatin-resistant cancer cells. Moreover, DN603/DN604-NBD targeted GSTP1 to suppress its expression level. By using the ROS scavenger NAC and the c-Jun N-terminal kinase (JNK) inhibitor SP600125 in advance, it was found that DN603/DN604-NBD could significantly increase the number of living cells and decrease the phosphorylation levels of JNK and c-Jun. The results indicated that DN603/DN604-NBD could produce higher levels of ROS to activate JNK-mediated signaling pathway, induce apoptosis in tumor cells to overcome cisplatin resistance. All the animal experiments were approved by Animal Ethics Committee of Southeast University (grant No. 20210303025). In vivo assays confirmed that DN603/DN604-NBD could inhibit the growth of A549 xenograft tumors with nearly no toxicity and fewer side effects. Taken together, DN603/DN604-NBD are investigated as two potential novel platinum (IV) prodrug candidates for anticancer therapy.

Objective:To evaluate neutrophil/lymphocyte ratio(NLR) and the model for end-stage liver disease-sodium(MELD-Na)score in predicting short-term prognosis of patients with HBV-related acute-on-chronic liver failure(HBV-ACLF).Methods:A total of 234 consecutive HBV-ACLF patients(194 males and 40 females, aged 23-85 years)admitted to Hangzhou Xixi Hospital from January 2019 to December 2021 were enrolled. According to the 12-week clinical outcomes, patients were divided into good prognosis group( n=141)and poor prognosis group( n=93). Univariate and multivariate Logistic regression were performed to identify independent risk factors for poor prognosis of HBV-ACLF patients. Receiver operating characteristics(ROC)curve was applied to evaluate the accuracy of risk factors in predicting short-term prognosis of HBV-ACLF patients. Results:The age [(48.7±11.9) vs. (52.5±9.9) years old, t=-2.59, P=0.011], proportion of males [78.0%(110/141) vs. 90.3%(84/93), χ2=5.99, P=0.014], total bilirubin[202.9(141.2, 287.6) vs. 320.0(224.4, 400.0) μmol/L, Z=-5.14, P<0.001], creatinine [71.0(59.0, 78.0) vs. 81.0(64.0, 111.0)μmol/L, Z=-3.98, P<0.001], international normalized ratio[1.66(1.52, 1.86) vs. 1.91(1.66, 2.27), Z=-5.46, P<0.001], leukocyte count[5.16(3.99, 6.95)×10 9/L vs. 6.57(4.83, 8.30)×10 9/L, Z=-4.14, P=0.001], NLR[2.77(2.02, 3.55) vs. 5.48(3.44, 8.53), Z=-8.48, P<0.001], MELD score[22.0(20.0, 24.0) vs. 26.0(24.0, 29.0), Z=-9.22, P<0.001], MELD-Na score[22.8(20.0, 25.6) vs. 29.0(25.0, 36.0), Z=-9.16, P<0.001], liver cirrhosis[77.3%(109/141) vs. 88.2%(82/93), χ2=4.41, P=0.036], hepatorenal syndrome[4/141(2.8%) vs. 12/93(12.9%), χ2=8.91, P=0.003] and the proportion of artificial liver treatment[21/141(14.9%) vs. 24/93(25.8%), χ2=4.30, P=0.038] were significantly elevated in poor prognosis group compared with survival group. Logistic regression analysis showed that NLR( OR=3.76, 95 %CI: 2.10-6.74, P<0.001)and MELD-Na score( OR=2.24, 95 %CI: 1.17-4.29, P=0.015) were independent risk factors for poor short-term prognosis of HBV-ACLF patients. The area under the ROC curve(AUC)of NLR, and MELD-Na for the short-term prognosis of HBV-ACLF patients was 0.792 and 0.822, respectively. The AUC of the combination of NLR with MELD-Na was 0.858, which was significantly higher than that of NLR( Z=-3.04, P=0.001) or MELD-Na score( Z=-2.16, P=0.031)alone. Based on the cut-off value of the combined model, patients were classified into high combined model score (≥0.04) group and low combined model score (<0.04) group, the survival rate of the high group was significantly higher than that of the low group( χ2=67.47, P<0.001). Conclusions:NLR and MELD-Na score are independent risk factors of the short-term prognosis of HBV-ACLF patients. The combination of NLR and MELD-Na score will be beneficial to predict the short-term prognosis of HBV-ACLF patients.

To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.
Animals ; Mice ; Medicine, Tibetan Traditional ; Network Pharmacology ; Molecular Docking Simulation ; Tandem Mass Spectrometry ; Toll-Like Receptor 4 ; Medicine, Chinese Traditional ; Mercury ; Drugs, Chinese Herbal/toxicity*

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C_(18) column(2.1 mm×50 mm, 1.9 μm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.
Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Tissue Distribution ; Drugs, Chinese Herbal