Objective To investigate the correlation between brain injury and spleen damage in a rat model of acute ischemic stroke and stasis interaction,and its effect on the MCP-1/CCR2 axis,and to provide an experimental basis for the mechanism of brain-spleen inflammatory coupling in spleen lesions caused by acute ischemic stroke.Methods Forty male SD rats were randomly divided into a sham group,carrageenan/yeast stasis syndrome group(carrageenan/yeast,CA/Y),middle cerebral artery occlusion group(MCAO),and middle cerebral artery stasis syndrome group(MCAO CA/Y)with 10 rats in each group.CA/Y and MCAO CA/Y groups were injected with 10 mg/kg carrageenan and 10 mg/kg intraperitoneally on the first day of modeling.2 mg/kg of dry yeast suspension were injected subcutaneously on the second day.MCAO and MCAO CA/Y groups were established by wire embolism on the second day.At 24 h after cerebral infarction modeling,the neurological deficit score was calculated in each group,the percentage of the cerebral infarction area was determined by TTC staining,the spleen weight was measured,and the correlation between the percentage of the cerebral infarction area and spleen weight was analyzed by the Spearman correlation coefficient.Furthermore,the pathological morphology of brain and spleen tissues was observed by hematoxylin-eosin(HE)staining,and chemotactic protein 1(MCP-1)and interferon-γ(IFN-γ)contents were measured in rat plasma by enzyme-linked immunosorbent assays.Western blot was used to detect chemokine C-C-motif receptor 2(CCR2)protein expression in the ischemic side of brain tissue.Results Compared with the sham group,the neurological deficit score,cerebral infarction area,and MCP-1 and IFN-γ contents in plasma were significantly increased(P＜0.01),spleen weight was decreased significantly(P＜0.01),and CCR2 protein expression in brain tissue was significantly upregulated(P＜0.05)in MCAO and MCAO CA/Y groups.Moreover,the area of cerebral infarction was increased significantly(P＜0.01),the spleen weight was decreased significantly(P＜0.01),and CCR2 protein expression in brain and spleen tissues was significantly upregulated(P＜0.05)Compared with the MCAO group,the area of cerebral infarction in the MCAO CA/Y group was significantly increased(P＜0.01)and the spleen weight was decreased significantly(P＜0.05).Spearman correlation analysis showed that the spleen weight was negatively correlated to the percentage of the cerebral infarction area(P＜0.01,r=-0.9711).Pathological morphology observation revealed that the pathological changes in the MCAO CA/Y group were the most serious,cerebral liquefaction necrosis foci were seen in the brain tissue cortex,arrangement of neuronal cells in the lesions was sparse and disordered with volume atrophy and a small number of vacuoles and nuclear solidification,most neuronal cells were degenerated and necrotic,microglia hyperplasia was obvious,small blood vessels were significantly increased,and interstitial lipid degeneration was severe.The density of periarterial lymph sheath cells in some of the spleen tissue was reduced and the marginal area is widened.Conclusions A correlation between brain and spleen injury was found after acute ischemic stroke with stasis and toxin syndrome,and the chemokine signaling axis of MCP-1/CCR2 might be involved in the mechanism of brain-spleen inflammation coupling.

Objective To establish a coronavirus(CoV)infection model using human nasal mucosa organoids for testing antiviral drugs and evaluate the feasibility of using human nasal mucosa organoids with viral infection as platforms for viral research and antiviral drug development.Methods Human nasal mucosa organoids were tested for susceptibility to SARS-CoV-2 and HCoV-OC43 pseudoviruses.In a P3 laboratory,nasal mucosa organoids were infected with the original strain of SARS-CoV-2 and 4 variant strains,and the infection conditions were optimized.The viral loads in the culture supernatants were measured at different time points using RT-qPCR,and immunofluorescence assay was employed to localize SARS-CoV-2 nucleocapsid protein to determine the type of the infected cells.In the optimized nasal mucosa viral infection model,the antiviral effects of camostat and bergamot extract(which were known to inhibit SARS-CoV-2)were tested and the underlying molecular mechanisms were explored.Results In the optimized nasal mucosa organoid models infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses,the viral load in the culture supernatants increased significantly during the period of 2 to 24 h following the infection,which confirmed infection of the organoids by both of the pseudoviruses.The nasal mucosa organoids could be stably infected by the original SARS-CoV-2 strain and its 4 variant strains,validating successful establishment of the viral infection model,in which both camostat and bergamot extract exhibited dose-dependent antiviral effects.Conclusions Human nasal mucosa organoids with SARS-CoV-2 infection can serve as platforms for screening and testing antiviral drugs,particularly those intended for nasal administration.

Objective To establish a coronavirus(CoV)infection model using human nasal mucosa organoids for testing antiviral drugs and evaluate the feasibility of using human nasal mucosa organoids with viral infection as platforms for viral research and antiviral drug development.Methods Human nasal mucosa organoids were tested for susceptibility to SARS-CoV-2 and HCoV-OC43 pseudoviruses.In a P3 laboratory,nasal mucosa organoids were infected with the original strain of SARS-CoV-2 and 4 variant strains,and the infection conditions were optimized.The viral loads in the culture supernatants were measured at different time points using RT-qPCR,and immunofluorescence assay was employed to localize SARS-CoV-2 nucleocapsid protein to determine the type of the infected cells.In the optimized nasal mucosa viral infection model,the antiviral effects of camostat and bergamot extract(which were known to inhibit SARS-CoV-2)were tested and the underlying molecular mechanisms were explored.Results In the optimized nasal mucosa organoid models infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses,the viral load in the culture supernatants increased significantly during the period of 2 to 24 h following the infection,which confirmed infection of the organoids by both of the pseudoviruses.The nasal mucosa organoids could be stably infected by the original SARS-CoV-2 strain and its 4 variant strains,validating successful establishment of the viral infection model,in which both camostat and bergamot extract exhibited dose-dependent antiviral effects.Conclusions Human nasal mucosa organoids with SARS-CoV-2 infection can serve as platforms for screening and testing antiviral drugs,particularly those intended for nasal administration.

ObjectiveTo observe and compare the electrocardiogram index， myocardial morphology， and connexin 43 （Cx43） expression of two rat models of acute cerebral infarction （ACI） due to stasis combined with toxin complicated with cerebral-cardiac syndrome （CCS）， and to provide experimental evidence for the research on the occurrence mechanism of cardiac diseases induced by ACI and the clinical diagnosis and treatment of CCS. MethodSixty SPF-grade male SD rats were randomized into six groups （n=10）： normal ， syndrome of stasis combined with toxin induced by carrageenin combined with dry yeast （CA/Y）， multi-infarct induced by micro-embolism （ME）， middle cerebral artery occlusion （MCAO）， CA/Y+ME， and CA/Y+MCAO groups. The model of syndrome of stasis combined with toxin was established by intraperitoneal injection with carrageenan （CA） at 10 mg·kg^-1 on the first day and subcutaneous injection with dry yeast （Y） suspension （2 mg·kg^-1） on the second day of modeling. Twenty-four hours after the modeling of ACI， the electrocardiograms （ECGs） of rats in each group were collected and the number/percentage （%） of abnormal ECG was calculated. The infarct area of the brain was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and myocardial injury was assessed by hematoxylin-eosin （HE） staining. Immumohistochemical staining and Western blot were employed to determine the expression of Cx43 in the myocardium. ResultA certain number of rats in each model group presented abnormal ECG. Compared with the normal group and CA/Y group， CA/Y+MCAO group had the highest rate of abnormal ECG （P<0.01）. Compared with the normal， CA/Y， ME， and CA/Y+ME groups， the CA/Y+ME and CA/Y+MCAO groups showed decreased amplitudes of P-wave and T-wave， shortened P-R interval， and extended Q-T interval， which were particularly obvious in the CA/Y+MCAO group （P<0.05， P<0.01） and in accordance with the cerebral infarction area and pathological changes. The expression of Cx43 was up-regulated in both CA/Y+ME and CA/Y+MCAO groups， especially in the CA/Y+MCAO group （P<0.01）. ConclusionThe two rat models of ACI due to stasis combined with toxin complicated with CCS can be used to study the mechanism of heart diseases caused by cerebrovascular diseases and the therapeutic effects of Chinese medicines with the functions of resolving stasis and detoxifying. Moreover， the CA/Y+MCAO method has higher abnormal electrocardiogram rate， severer myocardial pathological injury， and higher expression of Cx43 protein. The models can be chosen according to specific experimental purpose.

Objective To analyze the research status, hotspots of biofilms and periodontitis from 2013 to 2023 by bibliometric methods. Methods The literatures related to biofilms and periodontitis were searched in the Web of Science (Wos) database, and visualization software such as VOSviewer and CiteSpace were used to analyze the countries or regions, authors, institutions, journals and keywords. Results A total of 1 821 papers were included, and the results showed that the number of published papers increased year by year. The top three countries with the highest number of publications were the United States, Brazil and China; the top three institutions were Universidade de São Paulo, Harvard University and Forsyth Institute; the authors with the highest number of publications were Feres and Magda; among the top ten journals in terms of the number of publications, Journal of Periodontology had the highest number of publications (87 papers), followed by Plos One (69 papers) and Clinical Oral Investigations (51 papers). Oxidative stress, markers, adjunctive therapy and drug delivery were the main research hotspots; the frontiers mainly focused on quorum sensing, photodynamic therapy, reactive oxygen species, copper nanoparticles, and optical coherence tomography. Conclusion Researches on biofilms and periodontitis are growing year by year, and future research directions can focus on oxidative stress, adjuvant therapies, quorum sensing and photodynamic therapy.

Objective:To investigate preliminary results of chest wall reconstruction with local kiss flap following mastectomy for locally advanced breast cancer (LABC).Methods:Clinical data of the LABC patients receiving treatment at the Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University between June 2020 and July 2021 was retrospectively analyzed. All patients underwent modified radical mastectomy after neoadjuvant chemotherapy. And the local kiss flap was used for reconstruction of the secondary chest wall soft tissue defects. Two small local flaps were designed intraoperatively and harvested from inferior (flap A) and lateral (flap B) to the defect, respectively, resurfacing a large chest wall soft tissue defect side by side with primary closure of both two donor sites. The flap perfusion was routinely monitored postoperatively. Adjuvant systemic therapies were implemented based on both pre- and post-operative pathological results. And the adjuvant radiotherapy was started immediately after wound healed completely. All cases were followed up regularly.Results:A total of five female patients were included, with an average age of 53.4 (ranging from 41 to 71). Stage Ⅲ (T 3-4N 2-3M 0) breast cancer was diagnosed in all cases. After mastectomy, chest wall soft tissue defect was presented in all cases, ranging from 12.0 cm × 12.0 cm to 22.0 cm × 20.0 cm. The flap A measured from 7.0 cm × 7.0 cm to 14.0 cm × 13.0 cm and the flap B from 5.0 cm × 4.0 cm to 11.0 cm × 7.0 cm. Only 1 flap A suffered tip necrosis and the remnant flaps survived totally. All donor sites recovered uneventfully and no donor-site morbidity was noted. The mean post-operative follow-up period was 15.8 months (ranging from 13 to 20 months). No tumor recurrence or metastasis was noted in all patients, except one patient, who did not receive radiotherapy, suffered local recurrence 4 months after surgery. Conclusion:Given its simplicity and satisfying results, the local kiss flap is a feasible and reliable reconstructive option for chest wall soft tissue defect reconstruction after mastectomy in selected LABC patients.

Objective:To investigate preliminary results of chest wall reconstruction with local kiss flap following mastectomy for locally advanced breast cancer (LABC).Methods:Clinical data of the LABC patients receiving treatment at the Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University between June 2020 and July 2021 was retrospectively analyzed. All patients underwent modified radical mastectomy after neoadjuvant chemotherapy. And the local kiss flap was used for reconstruction of the secondary chest wall soft tissue defects. Two small local flaps were designed intraoperatively and harvested from inferior (flap A) and lateral (flap B) to the defect, respectively, resurfacing a large chest wall soft tissue defect side by side with primary closure of both two donor sites. The flap perfusion was routinely monitored postoperatively. Adjuvant systemic therapies were implemented based on both pre- and post-operative pathological results. And the adjuvant radiotherapy was started immediately after wound healed completely. All cases were followed up regularly.Results:A total of five female patients were included, with an average age of 53.4 (ranging from 41 to 71). Stage Ⅲ (T 3-4N 2-3M 0) breast cancer was diagnosed in all cases. After mastectomy, chest wall soft tissue defect was presented in all cases, ranging from 12.0 cm × 12.0 cm to 22.0 cm × 20.0 cm. The flap A measured from 7.0 cm × 7.0 cm to 14.0 cm × 13.0 cm and the flap B from 5.0 cm × 4.0 cm to 11.0 cm × 7.0 cm. Only 1 flap A suffered tip necrosis and the remnant flaps survived totally. All donor sites recovered uneventfully and no donor-site morbidity was noted. The mean post-operative follow-up period was 15.8 months (ranging from 13 to 20 months). No tumor recurrence or metastasis was noted in all patients, except one patient, who did not receive radiotherapy, suffered local recurrence 4 months after surgery. Conclusion:Given its simplicity and satisfying results, the local kiss flap is a feasible and reliable reconstructive option for chest wall soft tissue defect reconstruction after mastectomy in selected LABC patients.

Objective:To investigate changes in arterial acid-base and electrolytes after repeated episodes of ventricular fibrillation (VF) and defibrillation in a swine model.Methods:Sixteen Peking white swine, weighting (32±2.5) kg, were placed with temporary pacemaker electrodes via the left femoral vein into the right ventricle after anesthesia. Then VF was electrically induced by using a programmed electrical stimulation instrument. An arterial cannula was inserted into the left femoral artery to measure mean arterial blood pressure and cardiac output using a PiCCO monitor, with blood samples collected. The pigs were randomly divided into two group: the manual defibrillation group (MD, n=8) and the automated external defibrillation group (AED, n=8). The first defibrillation was attempted with the manufacturer’s dose (150 J) for 15 s after the successful induction of VF in the MD group. If spontaneous circulation was not recovered, 2-min chest compression and subsequent defibrillation (200 J) were attempted. For the AED group, the defibrillation was delivered following voice prompts of the AED. After the return of spontaneous circulation, the pig was allowed to stabilize for 30 min, followed by the induction of the next episode of VF. The above process was repeated five times. Arterial blood gas, cardiac biomarkers, and hemodynamic variables were measured at 30 min after the return of spontaneous circulation. Results:All pigs were successfully induced VF five times and defibrillated successfully. There were no significant changes in heart rate and mean arterial blood pressure between the two groups after repeated episodes of VF and defibrillation. Compared with baseline measurements, cardiac output tended to decrease after repeated episodes of VF and defibrillation but was not statistically significant (all P>0.05). There were no significant differences in arterial pH, HCO 3-, sodium, and lactic acid in the two groups between each measurement time point and baseline values after repeated VF (all P>0.05), but potassium levels in the two groups decreased with time, and the difference was statistically significant compared with the baseline measurement (all P<0.05). There were no significant differences in myoglobin, creatine kinase isoenzyme-MB, and cardiac troponin I for the two groups compared with baseline values after repeated episodes of VF and defibrillation or various episodes of VF between the two groups (all P > 0.05). Conclusions:Repeated episodes of VF and defibrillation have no significant effect on pH balance, but significantly decrease blood potassium. Clinical approaches (MD vs. AED) do not affect defibrillation effect, with no significant differences in hemodynamic variables and myocardial injuries.

Objective:To investigate the characteristics of primary catheter malposition (PCM) following totally implantable venous access port (TIVAP) implantation via the internal jugular vein (IJV) and management strategies.Methods:Clinical data of 587 consecutive breast cancer patients undergoing TIVAP implantation via the IJV performed by single team at the Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University from Aug 2017 to Aug 2022 was retrospectively analyzed.Results:A total of 593 TIVAP were implanted and PCM was found in 18 cases (3.0%). Four hundred and twenty five TIVAP were implanted via the right IJV with one PCM case (0.2%). One hundred and sixty eight TIVAP implantations were performed via the left IJV and PCM occurred in 17 cases (10.1%). The interventional management with a pigtail catheter was performed as a first-line strategy in 11 of the 18 PCM cases, with a success in 10 cases and failure in one. Three cases were successfully managed with the digital subtraction angiography (DSA)-guided open approach. Four cases underwent blind open procedure firstly and 2 suffered a failure.Conclusions:A higher incidence of PCM is found in TIVAP implantations via the left IJV than the right one. The interventional management with a pigtail catheter or the DSA-guided open procedure proves to be feasible for the correction of PCM.

Background: Domestic yaks are the most important livestock species on the Qinghai-Tibetan Plateau. Adult female yaks normally breed in the warm season (July to September) and enter anestrous in the cold season (November to April). Nevertheless, it is unclear how ovarian activity is regulated at the molecular level. Objectives: The peculiarities of yak reproduction were assessed to explore the molecular mechanism of postpartum anestrus ovaries in yaks after pregnancy and parturition. Methods: Sixty female yaks with calves were observed under natural grazing in Haiyan County, Qinghai Province. Three yak ovaries in pregnancy and postpartum anestrus were collected. RNA sequencing and quantitative proteomics were employed to analyze the pregnancy and postpartum ovaries after hypothermia to identify the genes and proteins related to the postpartum ovarian cycle. Results: The results revealed 841 differentially expressed genes during the postpartum hypoestrus cycle; 347 were up-regulated and 494 genes were down-regulated. Fifty-seven differential proteins were screened: 38 were up-regulated and 19 were down-regulated. The differential genes and proteins were related to the yak reproduction process, rhythm process, progesterone-mediated oocyte maturation, PI3K/AKT signaling pathway, and MAPK signaling pathway categories. Conclusions Transcriptome and proteomic sequencing approaches were used to investigate postpartum anestrus and pregnancy ovaries in yaks. The results confirmed that BHLHE40, SF1IX1, FBPX1, HSPCA, LHCGR, BMP15, and ET-1R could affect postpartum hypoestrus and control the state of estrus.