Tracheobronchial adenoid cystic carcinoma （TACC） is a low-grade malignant tumor originating from the airway mucosa. Despite its slow progression，it is characterized by high invasiveness，frequent recurrence，and a strong tendency for metastasis. Preclinical studies have shown that vascular-targeted therapy holds significant potential. However，an effective systemic treatment for TACC has not been established yet. This study explored TACC from the perspective of "Feiji" in traditional Chinese medicine （TCM） as the starting point. It deeply investigated the mechanisms of abnormal collaterals and tumor vascular recruitment and further elaborated on the theoretical connection between abnormal collaterals and tumor vascular recruitment. Firstly，collateral hyperactivity led to disordered and erratic pulmonary collaterals. Their abnormal structures were similar to the disorderly and tortuous nature of tumor （pseudo）angiogenesis. This resulted in imbalances in the functions of circulation，perfusion，and reverse injection of the pulmonary collaterals，and then led to unrestrained collateral dysfunction and the accumulation of pathogenic factors. Secondly，the remodeling of the extracellular matrix （ECM） and epithelial-mesenchymal transition （EMT） in TACC were critical processes in vascular co-option （VCO），representing the micro-level manifestation of the displacement of nutrient and defense. During this process，ECM remodeling made TACC cells more likely to hijack normal blood vessels，creating a complex vascular microenvironment conducive to tumor growth. In terms of treatment，this study proposed a TCM strategy of "regulating collaterals to expel pathogenic factors and nourishing collaterals to strengthen the healthy Qi"，and listed potential TCM. These were intended to regulate the Qi and blood in the collaterals，repair the functions of abnormal collaterals，and intervene in the vascular recruitment process of TACC. Future research should focus on improving the TCM clinical syndrome characteristics of TACC. Through modern molecular biology techniques，it is necessary to deeply analyze the micro-level pattern of vascular recruitment in TACC. This would enrich the understanding of the profound connection between abnormal collaterals and tumor vascular recruitment，providing empirical evidence for TCM-targeted therapies for vascular recruitment in TACC.

Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

Extracorporeal membrane oxygenation(ECMO)provides blood circulation with assisted breathing for patients with severe cardiopulmonary failure,and buys valuable time for the rescue of critical patients.However,extracorporeal membrane oxygenation is often associated with serious complications.Small animal models have the advantages of low price,wide source,high flexibility and good reproducibility,and are an effective platform for evaluating strategies for prevention and treatment of ECMO complications.In recent years,more and more experimental studies have been conducted using small animal ECMO models.In this paper,the current status of the construction and application of small animal ECMO models at home and abroad is summarized,in order to optimize the related strategies of small animal ECMO model construction and promote the application and development of small animal ECMO models.

Extracorporeal membrane oxygenation(ECMO)provides blood circulation with assisted breathing for patients with severe cardiopulmonary failure,and buys valuable time for the rescue of critical patients.However,extracorporeal membrane oxygenation is often associated with serious complications.Small animal models have the advantages of low price,wide source,high flexibility and good reproducibility,and are an effective platform for evaluating strategies for prevention and treatment of ECMO complications.In recent years,more and more experimental studies have been conducted using small animal ECMO models.In this paper,the current status of the construction and application of small animal ECMO models at home and abroad is summarized,in order to optimize the related strategies of small animal ECMO model construction and promote the application and development of small animal ECMO models.

Objective:To establish the "1+3" management module of high-value consumables in Operation Room and verify its application, so as to provide new ideas for cost management of consumables in Operation Room.Methods:The Operating Room team of Shenzhen Hospital of Southern Medical University designed a "1+3" management module in 2022, where "1" referred to the management process of high-value consumables in Operation Room, and "3" referred to the precise management of consumables in Operation Room warehouse, the management of closed-loop use of Operation Room consumables and adverse event management of consumables. Surgeries using high-value consumables in the Thoracic Surgery Department, Gastrointestinal Surgery Department, and Urology Department of the hospital were selected as the research objects. The surgeries using conventional consumables from January to June 2022 were set as the control group, and the surgeries implementing the "1+3" management module from July to December 2022 were set as the observation group. The number of consumables received by the itinerant nurses before the operation and the number of high-value consumables returned after the operation were compared between the two groups. And the number of missed and error charges for high-value consumables in the two groups were counted and compared.Results:The number of consumables received before operation in the control group was higher than that in the observation group, and the difference was statistically significant ( P<0.05). The number of high-value consumables returned in the observation group was less than that in the control group, and the difference was statistically significant ( P<0.01). The proportion of missed charges for consumables in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.01), but there was no statistically significant difference in the proportion of incorrect charges between the two groups ( P>0.05) . Conclusions:The "1+3" management module for high-value consumables in Operation Room makes the process of receiving, returning, and charging high-value consumables clear, with traceable data, achieving refined management of high-value consumables in Operation Room, reducing the number of high-value consumables returned to the warehouse and reducing the proportion of missed consumables, which is conducive to effective cost control in Operation Room.

Objective:To investigate the impact of small extracellular vesicles(sEVs) derived from perirenal adipose cells on the biological behavior of renal tubular epithelial cells under diabetic conditions and the underlying molecular mechanisms.Methods:Primary perirenal adipose cells were extracted from db/m and db/db mice for in vitro culture. The culture supernatant was collected and sEVs(NDM-sEVs PRAT-Adipo, DM-sEVs PRAT-Adipo) were extracted by ultracentrifugation. The sEVs were incubated with human renal tubular epithelial cell line(HK-2) to observe changes in their proliferation, apoptosis, autophagy, and epithelial-mesenchymal transition(EMT) levels. The protein composition of sEVs was analyzed using mass spectrometry to explore the molecular mechanisms. Results:CCK8 results showed that the proliferation level of HK-2 cells after DM-sEVs PRAT-Adipo intervention did not change significantly compared with the two control groups(Ctrl group and NDM-sEVs PRAT-Adipo intervention group). Western Blot(WB) results indicated that there were no significant changes in apoptosis levels(Bcl-2, Cleaved-caspase 3, Caspase 3) and autophagy levels(p62, LC3BⅠ, LC3BⅡ) in the DM-sEVs PRAT-Adipo intervention group compared with the two control groups. WB and immunofluorescence results demonstrated that DM-sEVs PRAT-Adipo intervention upregulated the expression levels of mesenchymal cell marker proteins(Vimentin, α-SMA, Snail2) and downregulated the expression level of epithelial cell marker protein ZO-1 in HK-2 cells compared with the two control groups. Mass spectrometry analysis of sEVs revealed that the differential proteins between DM-sEVs PRAT-Adipo and NDM-sEVs PRAT-Adipo were enriched in EMT-related pathways. Among them, the enrichment of thrombospondin(THBS1) in DM-sEVs PRAT-Adipo might be involved in the regulation of EMT in HK-2 cells. Conclusion:Under diabetic conditions, sEVs secreted by PRAT-derived adipocytes promote the upregulation of EMT in renal tubular epithelial cells, a process that may be mediated by the enrichment of THBS1 in sEVs.

Objective:To explore the challenges in the implementation of drug centralized volume-based procurement policies in hospitals and propose corresponding optimization suggestions.Methods:From August to December 2023, a purposive sampling was conducted to select 11 pharmaceutical experts from tertiary hospitals in China for Delphi method. The survey content included " policy recommendations for promoting the acceleration and expansion of national drug centralized procurement and retaining surplus medical insurance funds for centralized procurement" .Results:Survey participants gave feedback on a set of existing problems found in the implementation of drug centralized procurement policies and proposed corresponding optimization methods. Kendall′s W coefficient of the specialist consultation was 0.332( P<0.05), demonstrating good consistency and concentration of the expert opinions. Among the problems, the score of drug supply guarantee was the highest(mean value of importance was 4.45). At the same time, the recommendation of strengthening monitoring and early warning, coordination and dispatch, and effectively ensuring the supply of centralized drug procurement had the highest score and concentration(mean value of importance was 4.91, coefficient of variation was 0.06). Conclusions:Through Delphi method, this study revealed issues and optimization methods in the implementation of drug centralized procurement policies in hospitals. The findings could provide valuable insights for improvements in the pharmaceutical sector and future policy adjustments.

Objective:To investigate the screening values of immunocytochemical P16/Ki-67 double staining, P16 INK4α single staining and high-risk human papillomavirus (HR-HPV) testing for high-grade cervical lesions. Methods:The clinical data of 622 patients who underwent cervical thin-layer liquid-based cytology (TCT) and HR-HPV testing in General Hospital of Taiyuan Iron and Steel (Group) Co., Ltd. from March 2019 to July 2021 were retrospectively analyzed. The remaining cytological specimens were detected by P16/Ki-67 double staining and P16 INK4α single staining. Among them, 334 patients with TCT results suggesting atypical squamous cell of undetermined significance (ASCUS) and above and HPV-positive underwent colposcopy pathological biopsy. Using pathological results as reference, the positive predictive value, sensitivity, specificity and accuracy of P16/Ki-67 double staining, P16 INK4α single staining and HR-HPV testing for screening of high-grade squamous intraepithelial neoplasia (HSIL) and cervical cancer were compared. Results:Taking the results of histopathology as references, combined with the results of TCT, 31 of 622 patients were HSIL, of which 22 (71.0%) were positive for P16/Ki-67 double staining, 23 (74.2%) were positive for P16 INK4α single staining, and 25 (80.6%) were positive for HR-HPV testing; 4 cases were cervical cancer, and the positive rates of the three detection methods were all 100.0% (4/4). Among 622 patients, the positive rates of P16/Ki-67 double staining, P16 INK4α single staining and HR-HPV testing for screening of HSIL and cervical cancer were 13.99% (87/622), 25.40% (158/622) and 21.38% (133/622); the positive predictive values were 29.89%, 17.09% and 21.08%; the accuracies were 91.19%, 78.94% and 83.28%; the specificities were 89.77%, 77.98% and 82.46%; the sensitivities were 74.29%, 77.14% and 82.86%. The positive rate, positive predictive value, specificity and accuracy of P16/Ki-67 double staining were higher than those of P16 INK4α single staining and HR-HPV testing, and the differences were statistically significant ( z values were -5.062 and -3.418, 2.328 and 2.450, 5.436 and 3.570, 6.043 and 4.161, all P < 0.05); the sensitivity of HR-HPV testing was higher than that of P16/Ki-67 double staining and P16 INK4α single staining, but the differences were not statistically significant ( z values were -0.890 and 1.017, both P > 0.05). Conclusions:HR-HPV testing is more suitable for primary cervical lesion screening; P16/Ki-67 double staining can be used as a potential combined cell screening tool or an effective triage tool; P16 INK4α single staining has certain limitations.

Objective To evaluate the effects of ganglioside GM1 on hypoxic ischemic brain damage (HIBD) in neonatal rats and on the expression of potassium-chloride cotransporter 2 (KCC2) in hippocampus.Methods Seven-day-old Sprague-Dawley (SD) rats (n=72) were randomly divided into a sham group,an HIBD group and a ganglioside GM1 group.Each group was further divided into a 3 d subgroup and a 21 d subgroup according to the different detection index (n=12).Rat HIBD models were prepared according the Rice-Vannucci method.After HIBD,the ganglioside GM1 group was given ganglioside GM1 20 mg/ (kg ·d) by intraperitoneal injection for 3 d continuously.2-,3-,5-triphenyltetrazolium chloride (TTC) was preformed to evaluate the area of cerebral infarction of HIBD in each 3 d subgroup.Spontaneous activity recorder was used to observe the locomotor activity of the rats in the 21 d subgroups.Morris water maze test was conducted for assessment of rats' learning and memory abilities in the 21 d subgroups.Western blot analysis was employed to determine the alterations in KCC2 expression in hippocampus in all the 3 d and 21 d subgroups.Results Compared with the HIBD group (28.6％±5.2％),the ratio of cerebral infarction volume in the ganglioside GM1 group (11.3％±2.4％) was significantly reduced (P＜0.05).Compared with the HIBD group (289.6±61.3),the number of locomotor activities within 2 h in the ganglioside GM1 group (412.1±66.8) was significantly increased (P＜0.05).Compared with the HIBD group,the escape latency was significantly reduced,but the percentage time of target quadrant and the number of crossing the platform were significantly increased in the ganglioside GM1 group (P＜0.05).Three days and 21 days after HIBD,the expression of KCC2 in the ganglioside GM1 group was significantly higher than that in the HIBD group (P＜0.05).Conclusion Ganglioside GM1 may have a significant protective effect on HIBD in neonatal rats,and its mechanism may be related to regulation of the expression of KCC2 in hippocampus.

Objective To explore the effect of giving sedatives according to the circadian rhythm in prevention of occurrence of delirium and the prognosis of patients undergoing mechanical ventilation in intensive care unit (ICU). Methods A prospective double-blinded randomized controlled trial (RCT) was conducted. The patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University from July 2014 to February 2015, undergoing invasive mechanical ventilation over 12 hours were enrolled. All the patients were given fentanyl for analgesia, and they were randomly divided into simulated circadian clock group (study group, n = 35) and non-simulated circadian clock group (control group, n = 35). The patients in each group were subdivided into three subgroups according to the kinds of sedative drugs, namely dexmedetomidine group (n = 8), propofol group (n = 14), and dexmedetomidine combined with propofol group (combination group, n = 13). Visual analogue scale (VAS) standard and Richmond agitation-sedation scale (RASS) were used to control the analgesic and to quantify the depth of sedation by titrating the dose of sedative drugs, the simulated circadian clock was set to control the RASS score at 0-1 during the day, and -1 to -2 at night in study group. The RASS score in the control group was set at -1 to -2 day and night. The urine 6-hydroxy acid melatonin (aMT6s) levels at different time points in the first diurnal rhythm (06:00, 12:00, 18:00, 24:00) were determined by enzyme linked immunosorbent assay (ELISA). The incidence of delirium, severe hypotension, severe bradycardia and other adverse reactions, duration of mechanical ventilation and the time of extubation, length of ICU stay, amount of sedative and analgesic drugs used were recorded. The correlation between delirium and other indexes was analyzed by using Spearman correlation analysis. Results ① There were no significant differences in gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score among groups. ② Urine aMT6s levels did not show circadian rhythm in both groups, aMT6s level at 06:00 in study group showed an increasing tendency as compared with the control group, but the difference was not statistically significant. ③ Compared with the control group, the incidence of delirium was significantly lowered in the study group (14.3% vs. 37.1%, P = 0.029), but no significant differences were found in the incidence of severe hypotension or severe bradycardia (20.0% vs. 25.7%, 11.4% vs. 20.0%, both P > 0.05). In simulated circadian clock group, the incidence of delirium in dexmedetomidine group was significantly lower than that of the propofol group (6.3% vs. 32.1%, P < 0.05). ④ Compared with control group with the same sedative, the duration of mechanical ventilation, extubation time, length of ICU stay were significantly shortened, and the dosage of sedative drugs used was reduced in study group (all P < 0.05). In simulated circadian clock group, the duration of mechanical ventilation in dexmedetomidine group was significantly shorter than that of propofol group and combination group (hours: 75.75±26.78 vs. 102.00±26.31 and 100.31±25.38, both P < 0.05), and the length of ICU stay was significantly shorter than that of propofol group (days: 5.75±1.04 vs. 7.00±1.52, P < 0.05). ⑤ The occurrence of delirium was positively correlated with duration of mechanical ventilation (r = 0.705), extubation time (r = 0.704), length of ICU stay (r = 0.666, all P = 0.000), and no correlation was found between the occurrence of delirium and aMT6s level at 06:00, 12:00, 18:00, and 24:00 (r = -0.135, r = 0.163, r = 0.269, r = -0.077, all P > 0.05). Conclusions Administration of sedatives according to simulating circadian time could decrease the duration of mechanical ventilation, extubation time, and the length of ICU stay, decrease the dosage of sedative drugs, and reduce the incidence of delirium. Dexmedetomidine could reduce the incidence of delirium, and improve the prognosis of patients. Trial registration Registration of clinical trials in China, ChiCTR-IPR-15006644.