Lung transplantation is the ultimate therapeutic option for end-stage pulmonary diseases such as interstitial pneumonia, chronic obstructive pulmonary disease and pneumoconiosis. Currently, the shortage of allogeneic lung donors significantly limits the opportunity for end-stage lung disease patients to receive lung transplantation. In recent years, with the rapid development of biomedical engineering technologies, especially the major breakthroughs in genetic modification and cloning, xenogeneic lung transplantation has shown important potential for clinical translation. Among them, genetically modified pigs have become the most promising xenogeneic lung source due to the close similarity of organ size and physiological characteristics to humans, and the ability to perform targeted gene knockouts (such as α-Gal antigen knockout) to reduce the occurrence of hyperacute rejection. This article focuses on the research progress of porcine xenogeneic lung transplantation, systematically reviews the latest achievements and challenges in animal experiments and human trials, and introduces the technical experience accumulated by Shenzhen Third People's Hospital in the porcine-to-monkey xenogeneic lung transplantation model, in the hope of providing practical references for future research in this field.

OBJECTIVE: To observe the effects of point-moxibustion with Zhuang medicinal thread on differentially expressed genes (DEGs) in the dorsal root ganglion (DRG), tissue morphology, and the expression of Fc epsilon RI (FcεRI) pathway proteins spleen tyrosine kinase (Syk) and membrane spanning 4-domain A2 (MS4A2) in rat model of postherpetic neuralgia (PHN), and to explore the potential mechanism by which this therapy alleviates pain sensitization. METHODS: Thirty-nine male Sprague-Dawley (SD) rats were randomly divided into a control group, a model group, and a moxibustion group, with 13 rats in each group. The PHN model was established in the model and moxibustion groups by intraperitoneal injection of resiniferatoxin. In the moxibustion group, bilateral L₄-L₆ "Jiaji" (EX-B2) points were treated with point-moxibustion with Zhuang medicinal thread from day 7 post-modeling, with two cones per acupoint per session, every other day for a total of 10 sessions. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured at 1 day before modeling and on days 1, 4, 7, 13, 19, and 25 after modeling. After intervention, HE staining was used to observe DRG morphology. RNA sequencing was performed to analyze DEGs in DRG and conduct bioinformatics analysis. The expression of Syk and MS4A2 mRNA and proteins in the FcεRI pathway in DRG was detected by quantitative PCR and Western blot. RESULTS: Compared with the control group, the model group exhibited decreased MWT (P<0.05) and increased TWL (P<0.05); histopathological analysis revealed neuronal atrophy, nuclear displacement, and intracellular vacuoles, with a slightly loose arrangement; the RNA-Seq identified 3,207 DEGs (1,997 upregulated and 1,210 downregulated); the mRNA and protein expression levels of Syk and MS4A2 were significantly increased (P<0.01). Compared with the model group, the moxibustion group showed increased MWT (P<0.05) and decreased TWL (P<0.05), with relatively normal neuronal morphology; the RNA-Seq identified 426 DEGs (250 upregulated and 176 downregulated); the mRNA and protein expression levels of Syk and MS4A2 were significantly decreased (P<0.05). Venn diagram analysis identified 156 DEGs that showed a reversal in expression trends after treatment, including Syk and MS4A2, which are associated with pain sensitization. KEGG pathway analysis indicated that these DEGs were primarily enriched in the FcεRI pathway. CONCLUSION Point-moxibustion with Zhuang medicinal thread could alleviate pain sensitization in PHN rats, possibly by inhibiting the FcεRI signaling pathway and downregulating the expression of Syk and MS4A2.
Animals ; Rats, Sprague-Dawley ; Male ; Rats ; Moxibustion ; Neuralgia, Postherpetic/physiopathology* ; Syk Kinase/metabolism* ; Acupuncture Points ; Humans ; Ganglia, Spinal/metabolism* ; Signal Transduction

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Objective To investigate the effect of Zhuang medicated thread moxibustion on postherpetic neuralgia model rats,and to verify the mechanism of Th1/Th2/Th17 cytokine balance regulation in central nervous system.Methods 50 SD rats were randomly divided into blank group,model group,thread-moxibustion without drugs group,Zhuang medicated thread moxibustion group and pregabalin group,with 10 rats in each group.Except for blank group,the rat model of postherpetic neuralgia was induced by a single intrapitoneal injection of resin-toxin(RTX).After successful modeling,each group was given corresponding treatment for 21 days.The Mechanical Pain Threshold(PWT)and Thermal withdrawal latency(TWL)were detected 3 days before modeling,1,4 and 7 days after modeling,and 3,7,14 and 21 days after intervention.After the intervention,extract spinal cord tissue,Flow cytometry was used to detect changes in the proportion of Th1/Th2/Th17 cells;The mRNA expression levels of IFN-γ,IL-2,IL-4,IL-10,IL-17 and IL-22 were detected by qPCR;The positive expressions of IFN-γ,IL-2,IL-4,IL-10,IL-17 and IL-22 were observed by immunohistochemistry.The protein expressions of IFN-γ,IL-2,IL-4,IL-10,IL-17 and IL-22 were detected by Western blot to elucidate the regulation effect of this therapy on the equilibrium mechanism.Results After intrapitoneal injection of resin-toxin,the PWT of rats showed a downward trend,while the TWL showed an upward trend,showing the separation of heat and pain,which was consistent with the clinical manifestations of PHN.After Zhuang medicated thread moxibustion therapy,PWT increased and TWL decreased in PHN rats,which reduced the separation trend of heat and pain.Thread-moxibustion without drugs group,Zhuang medicated thread moxibustion group and pregabalin group can promote Th1 response in the central nervous system(spinal cord),increase the proportion of CD4+IL-2+cells and the contents of IFN-γ and IL-2 in the spinal cord tissue,and up-regulate the expression of IFN-γ and IL-2 mRNA and protein.Meanwhile,Th2 and Th17 responses in the central nervous system were inhibited,and the proportions of CD4+IL-4+and CD4+IL-17A+cells and the contents of IL-4,IL-10,IL-17 and IL-22 in the spinal cord tissue were reduced.The mRNA and protein expressions of IL-4,IL-10,IL-17 and IL-22 were down-regulated.In addition,Zhuang medicated thread moxibustion group and pregabalin group had similar efficacy in correcting Th1/Th2/Th17 lymphocyte imbalance in the central nervous system,and both were better than the Thread-moxibustion without drugs group.Conclusion Zhuang medicated thread moxibustion can improve the separation trend of heat and pain in postherpetic neuralgia rats,which may be achieved by regulating Th1/Th2/Th17 cell balance and related cytokine levels.

The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

Objective:To formulate the Nursing standards of clinical practice of critical care ultrasonography (referred to as the Standards), so as to provide recommendations for the application of ultrasound in intensive care nursing practice. Methods:Based on the experience of intensive care ultrasound nursing practice and literature research, combined with the consensus recommendations of intensive care ultrasound, the critical care ultrasound study group formed the first draft of the Standards. After expert interview, consensus discussion, two rounds of Delphi expert letter consultation and other methods, the content of the Standards was revised and improved, and the final draft of the Standards was formed. Results:The Standards included four parts, such as basic application of intensive care ultrasound, nursing evaluation standard of intensive care ultrasound guidance, nursing operation process guided by ultrasound and intensive care ultrasound training. Conclusions:The establishment of Standards is scientific and practical, which can provide guidance for nursing practice of clinical operation technology of critical care ultrasonography.

Objective:To analyze the efficacy, safety and prognostic factors of immune checkpoint inhibitors in the treatment of recurrent and metastatic cervical cancer.Methods:A total of 87 patients with recurrent and metastatic cervical cancer admitted to the First Affiliated Hospital of Soochow University from January 2018 to June 2022 were retrospectively analyzed. They were divided into non immunotherapy group ( n=32) and immunotherapy group ( n=55) according to whether immune checkpoint inhibition was applied after recurrence and metastasis. The disease control rate (DCR), progression free survival (PFS), overall survival 1 (OS1, date of pathology diagnosis to the end of follow-up or time of death), overall survival 2 (OS2, time of first immunotherapy/non-immunotherapy to the end of follow-up or time of death), safety and prognostic factors of the two groups were analyzed and compared. Results:In 87 patients with recurrent and metastatic cervical cancer, the DCR of the non immunotherapy group and immunotherapy group were 53.1% (17/32) and 72.7% (40/55) respectively ( χ2=3.44, P=0.064). The median OS1 of the non immunotherapy group was 51.0 months, while the immunotherapy group did not reach the median OS1, with a statistically significant difference ( χ2=7.50, P=0.006). The median OS2 of the non immunotherapy group was 28.0 months, while the immunotherapy group did not reach the median OS2, with a statistically significant difference ( χ2=7.07, P=0.008). The median PFS of the non immunotherapy group and immunotherapy group were 18.0 months and 23.0 months respectively, with no significant difference ( χ2=0.01, P=0.915). In the immunotherapy group, 70.9% (39/55) of patients received immune checkpoint inhibitors as first-line treatment and 29.1% (16/55) received as second-line and above treatment. Both groups of patients did not achieve median OS2, with median PFS of 23.0 and 17.0 months respectively, and there were no statistically significant differences ( χ2=0.94, P=0.333; χ2=2.00, P=0.158) ; 38.2% (21/55) of patients received immune checkpoint inhibitor combined with local radiotherapy, 61.8% (34/55) patients did not receive radiotherapy. And neither group of patients achieved median OS2, with median PFS of 19.0 and 25.0 months respectively, with no statistically significant differences ( χ2=0.62, P=0.432; χ2=0.01, P=0.906). The incidences of grade 1-2 hematuria and hypothyroidism in the non immunotherapy group and immunotherapy group were 53.1% (17/32) vs. 27.3% (15/55, χ2=5.82, P=0.016), 3.1% (1/32) vs. 21.8% (12/55, χ2=4.19, P=0.041) respectively. The incidence of myelosuppression in the non immunotherapy group [grade 1-2: 59.4% (19/32), grade 3-4: 34.4% (11/32) ] was significantly different from that in the immunotherapy group [grade 1-2: 80.0% (44/55), grade 3-4: 3.6% (2/55) ; Z=3.50, P<0.001]. There were no statistically significant differences between creatinine increase, glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase increase, lymphocyte decrease, hypoproteinemia, proteinuria, rash, fatigue (all P>0.05). Univariate regression analysis showed that the use of immune checkpoint inhibitor was an independent protective factor affecting the prognosis of patients ( HR=0.31, 95% CI: 0.12-0.77, P=0.012) . Conclusion:Whether used as first-line or second-line or above treatment, the use of immune checkpoint inhibitors in patients with recurrent and metastatic cervical cancer prolongs their OS1, OS2, and has good safety. The application of immune checkpoint inhibitors is an independent protective factor affecting the prognosis of patients.

OBJECTIVES: The aim of this study was to evaluate the disease burden of prostate cancer (PC) and assess key influencing factors associated with the disease expenditures of PC in the United States. METHODS: The total deaths, incidence, prevalence, and disability-adjusted life-years of PC were obtained from the Global Burden of Disease Study 2019. The Medical Expenditure Panel Survey was used to estimate healthcare expenditures and productivity loss and to investigate patterns of payment and use of healthcare resources in the United States. A multivariable logistic regression model was conducted to identify key factors influencing expenditures. RESULTS: For patients aged 50 and older, the burden for all age groups showed a modest increase over the 6-year period. Annual medical expenditures were estimated to range from US$24.8 billion to US$39.2 billion from 2014 to 2019. The annual loss in productivity for patients was approximately US$1,200. The top 3 major components of medical costs were hospital inpatient stays, prescription medicines, and office-based visits. Medicare was the largest source of payments for survivors. In terms of drug consumption, genitourinary tract agents (57.0%) and antineoplastics (18.6%) were the main therapeutic drugs. High medical expenditures were positively associated with age (p=0.005), having private health insurance (p=0.016), more comorbidities, not currently smoking (p=0.001), and patient self-perception of fair/poor health status (p<0.001). CONCLUSIONS From 2014 to 2019, the national real-world data of PC revealed that the disease burden in the United States continued to increase, which was partly related to patient characteristics.

Objective:To investigate the serum and follicular fluid levels of sterol regulatory element-binding protein 1c(SREBP-1c), leucine-rich α-2-glycoprotein 1(LRG1) and the correlation with insulin resistance(IR) in non-ovarian etiology infertility patients and polycystic ovary syndrome(PCOS) patients with or without IR.Methods:Forty-nine PCOS patients and 66 infertility patients with non-ovarian etiology were collected in this retrospective study, homeostasis model assessment for insulin resistance(HOMA-IR) was used to evaluate IR, and were divided into control group( n=36), IR group( n=30), PCOS alone group( n=28) and PCOS-IR group(PCOS with IR group, n=21). The concentrations of serum, follicular fluid LRG1 and SREBP1c levels in each group were compared, and their correlation with relevant hormones and glycolipid metabolism were analyzed. Results:The levels of serum, follicular fluid LRG1 and SREBP1c in IR group, PCOS alone group and PCOS-IR group were significantly higher than those in control group; The PCOS-IR group showed a more significant increase in the levels of serum, follicular fluid LRG1 and SREBP1c( P<0.05). Correlation analysis showed that serum, follicular fluid LRG1 was positively correlated with body mass index, fasting plasma glucose(FPG), fasting insulin(FINS), triglycerides(TG), and HOMA-IR( P<0.05). Serum, follicular fluid SREBP1c was positively correlated with body mass index, FPG, FINS, TG, total cholesterol, LDL-C, LH, total teststerone, DHEAS, FAI, and HOMA-IR( P<0.05). Binary logistic regression analysis showed that serum SREBP1c was a risk factor for PCOS( P<0.05). Conclusion:The serum and follicular fluid levels of LRG1 and SREBP-1c were elevated in PCOS patients, especially in those with IR. The elevated levels of serum and follicular fluid LRG1 and SREBP-1c may be associated with IR and glucose-lipid metabolism abnormalities in PCOS patients. Serum LRG1 and SREBP-1c levels may serve as new indicators for predicting IR, early diagnosis, and intervention in PCOS patients.

Objective:To analyze the clinical characteristics of children with 2019 novel coronavirus (2019-nCoV) infection in Putian City, and to provide a reference for the diagnosis and treatment of children with 2019-nCoV infection.Methods:Clinical characteristics, laboratory examination, pulmonary compated tomography findings, treatment, and clinical outcomes of 78 children with 2019-nCoV infection who were admitted to Putian University Affiliated Hospital Medical Group Putian City Children′s Hospital from September 10 to October 20, 2021 were retrospectively collected and analyzed.Results:Of the 78 children included in the analysis, two cases (2.6%) were asymptomatic infection, 36 cases (46.2%) were mild and 40 cases (51.3%) were ordinary. Five children were vaccinated against 2019-nCoV. The main symptoms were fever (24 cases), cough (13 cases), and fatigue (nine cases). A total of 34 cases (43.6%) had neutropenia, 29 cases (37.2%) had lymphopenia, 36 cases (46.2%) had D-dimer increase, 38 cases (48.7%) had hypokalemia, 27 cases (34.6%) had hypoglycemia and 11 cases (14.1%) had elevated creatine kinase isoenzyme. The neutropenia mostly occurred two to four days after admission. Fifty-six cases (71.8%) showed pulmonary computed tomography abnormalities. The cycle threshold of virus open reading frame ( ORF)1 ab was 20.90±7.15 and the cycle threshold of N gene was 20.29±7.78 in the first nucleic acid detection of 78 children after admission. The time of nucleic acid negative conversion of the 78 children was (20.73±6.94) days. IgM antibody titer in five vaccinated children was 0.36 (0.34, 4.89) and IgG antibody was 10.42 (0.50, 19.42). IgM antibody titer was 1.82 (1.66, 8.12) and IgG antibody was 76.63 (16.92, 79.84) in cases with disease duration ≥10 days. Nine children (11.5%) had resurgence of virus and were sent to the isolation site. All the other children were cured and discharged from hospital. Conclusions:Children with 2019-nCoV infection have mild clinical symptoms, and some children have lymphopenia, neutropenia, and D-dimer elevation during the course of the disease. The overall prognosis is good. The children vaccinated against 2019-nCoV have higher antibody levels.