BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

The European Association for Cardio-Thoracic Surgery (EACTS) has recently updated and published the "2024 EACTS guidelines on perioperative medication in adult cardiac surgery". Based on the latest evidence, the guidelines have been updated in multiple aspects including underlying disease management, antithrombotic medication, arrhythmia treatment and other supportive care, etc. This paper aims to summarize and interpret the guidelines, in order to promote clinicians’ understanding and optimize perioperative medical treatment in adult cardiac surgery.

Objective To investigate prokaryotic expression of the antigen sequence (amino acids 59-145) of mouse leukemia-related protein 16 (LRP16) protein and preparation of rabbit anti-mouse LRP16 polyclonal antibody. Methods The prokaryotic expression plasmid pLS962-LRP16 was constructed by the molecular cloning method and transferred into E.coli Rosetta to express LRP16 protein induced by IPTG. The recombinant protein was purified using Ni-NTA affinity columns followed by gel filtration chromatography. New Zealand white rabbits were immunized with the purified antigen to generate polyclonal antiserum, with antibody titer quantified by ELISA. Antigen-specific IgG was affinity-purified using Sepharose-coupled LRP16 and validated through Western blot and immunofluorescence assays. Results SDS-PAGE analysis confirmed insoluble expression of the LRP16 fusion protein as inclusion bodies. ELISA demonstrated exceptional antiserum titer (1:256 000). Western blot and immunofluorescence verified that the polyclonal antibody could specifically recognize endogenous LRP16 in murine tissues. Conclusion The prokaryotic expression of the LRP16 gene is successfully achieved, and the rabbit anti-mouse LRP16 polyclonal antibody exhibiting high specificity is prepared. This lays the foundation for further studies on the function of the LRP16 gene.
Animals ; Rabbits ; Mice ; Antibodies/immunology* ; Escherichia coli/metabolism* ; Enzyme-Linked Immunosorbent Assay ; Blotting, Western ; Antibody Specificity

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Objective:To compare the efficacy of linaclotide and procalcitide in the treatment of adult constipation IBS-C.Methods:A retrospective study was conducted on 80 IBS-C patients admitted from May 2021 to May 2024.All patients were treated with novel secretagogues,and were divided into four groups according to the different treatment methods:linarotinib group and Pucanapide group,with 40 patients in each group.The clinical efficacy of oral administration of 290 μg of Nallotide capsules and 3 mg of Pucanapeptide in the Linalotide group and Pucanapeptide group was compared after one month of continuous treatment.The scores of IBS-C symptoms related to stool frequency,stool characteristics,upper abdominal pain,early satiety,and bloating were evaluated before and Post-treatment.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of vasoactive intestinal peptide(VIP),substance P(SP),5-hydroxytryptamine(5-HT),motilin,and gastrin IBS-C related serum markers in feces.The 16s rDNA fluorescence quantitative polymerase chain reaction method was used to detect Escherichia coli and lactate in feces.Compare the incidence of adverse reactions between the two groups based on the levels of Bacillus and Bifidobacterium.Results:There was no difference in the total effective rate between linagliptin group and Pucanotide group(P＞0.05);Post-treatment,the fecal frequency scores of the linaclotide group and the procalcitonin group were higher than pretherapy,while the fecal characteristics,upper abdominal pain,early satiety,and fullness scores were lower than pretherapy(P＜0.05).There was no difference in the fecal frequency,fecal characteristics,early satiety,and fullness scores between the linaclotide group and the procalcitonin group(P＞0.05),and the upper abdominal pain score of the linaclotide group was lower than that of the procalcitonin group(P＜0.05);Post-treatment,VIP,SP,5-HT,motilin and gastrin levels in linagliptin group and Pucanotide group were all lower than that pretherapy(P＜0.05),and there was no significant difference between linagliptin group and Pucanotide group(P＞0.05);Post-treatment,the levels of Escherichia coli in the linaclotide group and the procaine group were lower than pretherapy,while the numbers of Lactobacilli and Bifidobacteria were higher than pretherapy(P＜0.05).There was no difference between the linaclotide group and the procaine group(P＞0.05);There was no difference in the incidence of headache,bloating/abdominal pain between the linaclotide group and the procaine group(P＞0.05),and the incidence of diarrhea in the procaine group was lower than that in the linaclotide group(P＜0.05).Conclusion:Linalotide and Pucanatide have similar therapeutic effects in treating adult IBS-C,both of which can improve patients' clinical symptoms,serum biomarker levels,and intestinal microbiota structure.However,Linalotide has a better effect on improving abdominal pain,while Pucanatide can reduce the risk of diarrhea.Therefore,the clinical application of different new secretagogue drugs can be determined based on individualized symptoms and diarrhea risk of patients.

Objective Based on the general belief that the tongue characteristics of blood stasis constitution is"purple tongue,tortuous sublingual vessels",this study systematically summarized blood stasis tongue characteristics using artificial intelligence image processing combined with expert evaluation.Methods A physical questionnaire survey was conducted on 1275 college students,and 100 cases were randomly selected from the blood stasis constitution group and the mild constitution group.After collecting the tongue images,Unet,OpenCV,YOLOv5 and YOLOv8 algorithms combined with expert evaluation method were used to extract and analyze the tongue features of the two groups.By comparing the differences of tongue image characteristics between the blood stasis constitution group and the mild constitution group,the tongue characteristics of blood stasis constitution were systematically summarized.Results Compared with the mild constitution group,the proportion of light dark tongue and light purple tongue in the blood stasis constitution group was significantly higher(P＜0.05).The I value,L value and a value of the tongue area 1 in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05).The S value and a value of area 2 and area 3 were significantly larger(P＜0.05),and the I value,L value,a value and b value of area 5 were significantly smaller(P＜0.01,P＜0.05).Compared with the mild constitution group,the proportion of tooth marks tongue in the blood stasis constitution group was significantly higher(P＜0.01),the proportion of cracked tongue in the blood stasis constitution group was significantly larger(P＜0.05),and the number of tooth marks,crack area,relative height of crack and relative width of crack in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05).Compared with the mild constitution group,the I value,L value,a value and b value of tongue coating area 1 in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05),the I value,L value,S value,a value and b value of tongue coating area 2 were significantly larger(P＜0.01,P＜0.05),the I value,S value,a value and b value of tongue coating area 3 were significantly larger(P＜0.01,P＜0.05),the b value of tongue coating area 4 was significantly larger(P＜0.05),the S value,a value and b value of tongue coating area 5 were significantly larger(P＜0.01,P＜0.05).The proportion of thick tongue coating and greasy tongue coating in the blood stasis group was significantly higher than that in the gentleness group(P＜0.05).Compared with the mild constitution group,the proportion of tortuous,thickened and nodular sublingual collaterals in the blood stasis constitution group was significantly larger(P＜0.01,P＜0.05).The a value,I value,S value,b value and relative width of sublingual collaterals in the blood stasis constitution group were significantly larger(P＜0.01,P＜0.05).Conclusion On the basis of the general belief that the characteristics of blood stasis constitution tongue are dark purple tongue and dark purple sublingual collaterals/varicose veins/thickening,blood stasis constitution people also have new tongue characteristics,such as redder tips and edges,more teeth marks and fissures,thicker and greasier coatings,and yellow fur.These findings offer new insights for"to identify the constitution of traditional Chinese medicine and prevent diseases by observing the tongue manifestation".

Objective To investigate the mechanism by which ginkgetin attenuates H9c2 cells injury.Methods H9c2 cells were divided into five groups:control,lipopolysaccharide(LPS),LPS+3-methyladenine(3-MA,an autophagy inhibitor),LPS+ginkgetin,and LPS+3-MA+ginkgetin.Cell viability and cytotoxicity were assessed using the cell CCK-8 and lactate dehydrogenase assays,respectively.Immunofluorescence staining for LC3,monodansylcadaverine staining for autophagosomes,and flow cytometry were used to measure apop-tosis rates.Quantitative real-time PCR was performed to measure the expression of NR4A2/p53/Bax pathway.Western blotting was used to detect the expression of NR4A2,p53,Bax,LC3,Beclin-1,p62,cleaved caspase-3,and Bcl-2 proteins.Results Compared to the LPS group,ginkgetin significantly increased LC3 fluorescence levels and monodansylcadaverine fluorescence intensity,decreased apoptosis,upregulated NR4A2,downregulated p53 and Bax,increased LC3,Beclin-1,and Bcl-2 proteins,and decreased p62 and cleaved caspase-3(P＜0.05).The autophagic inhibitor,3-MA,confirmed that ginkgetin protected H9c2 cells from LPS-induced apoptosis via autophagy regulation.Conclusion Ginkgetin mitigated cardiomyocyte injury by enhancing autophagic flux and alleviating LPS-induced H9c2 cells apoptosis by modulating the NR4A2/p53/Bax pathway.

Purpose To investigate the clinicopathological features,diagnosis,and molecular genetic characteris-tics of central nervous system(CNS)high-grade neuroepithelial tumors with BCOR alterations.Methods Five cases of CNS high-grade neuroepithelial tumors harboring BCOR alterations were collected.Using immunohistochemistry and molecular detection to analyze its clinical and histological characteristics,and review relevant literatures.Results A-mong the 5 patients,3 cases with EP300 ∷ BCOR tumor(male-to-female ratio 2∶1).These tumors were located in supratentorial regions(right temporal lobe,right frontotemporal lobe,and right frontal lobe).The 2 patients with BCOR-ITD tumors were younger,both with tumors located in the left cerebellum.Imaging studies revealed well-defined large mass lesions in all cases.Histologically,all 5 cases tumor exhibited ependymoma-like or oligodendroglioma-like morphology,featuring uniformly oval or round cells.Focal areas showed increased cellular density,nuclear enlarge-ment,and readily identifiable mitotic figures indicative of anaplastic features.A rich capillary network was frequently observed in the stroma.Palisading necrosis,microcystic changes,and microcalcifications were present in 3 cases.Im-munohistochemically,all 5 cases consistently expressed vimentin and CD56,focal Olig-2 positivity,variable S-100 ex-pression,and were uniformly negative for GFAP.BCOR immunostaining was weakly positive in 1 case with an EP300∷ BCOR fusion and strongly positive in 2 cases with BCOR-ITD.NGS identified an EP300 ∷ BCOR fusion in 3 cases,and Sanger sequencing confirmed the ITD in exon 15 of BCOR gene in 2 cases.During a follow-up period of 8 to 77 months,one pediatric patient with a BCOR-ITD tumor died,while the remaining four patients were alive with no evi-dence of recurrence or metastasis.Conclusion BCOR-ITD and EP300 ∷ BCOR fusion tumors are similar in morphology and immunophenotype,and the incidence rate of BCOR fusion tumors may be underestimated.NGS sequencing based on DNA and RNA and DNA methylation spectrum analysis are helpful for accurate diagnosis of this type of tumor.

As the incidence of autism rises annually,its unknown pathogenesis makes it challenging to treat the varied repetitive and stereotyped behaviors that characterize its core symptoms.The striatum is an important brain region for the control of locomotor behaviors,featuring a unique mosaic structure,complex neural origin,and finely regulated developmental process that is highly susceptible to genetic and environmental influences.Both clinical and basic studies have indicated that abnormal development of the striatal nuclei may contribute to the pathogenesis of these repetitive stereotyped behaviors in autism.Clinical imaging data have primarily identified gross anatomical variations in the stratum(e.g.,its general outline),but lack the resolution necessary to detect the cellular and subcellular alterations within the region.By introducing the abnormalities in the spatiotemporal development of the striatum and their links to the characteristic behaviors of autism,this review aims to advance our understanding of the role of the striatum in autism pathogenesis and to inform future animal studies and clinical research.