Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

FH-deficient renal cell carcinoma(FH-dRCC) is a rare and highly aggressive subtype of renal cell carcinoma. This tumor is often associated with hereditary leiomyomatosis and renal cell carcinoma(HLRCC) syndrome. Its pathogenesis involves biallelic inactivation of the FH gene, leading to the accumulation of fumarate, which disrupts cellular metabolic balance and DNA repair processes, thereby driving tumorigenesis. This paper reports a patient with FH-dRCC. The patient underwent radical nephrectomy but experienced early postoperative recurrence and liver metastasis. Despite multiple lines of systemic therapy, including targeted and combination immunotherapy, which initially achieved radiographic response, the patient eventually died as the disease progressed with extensive metastases. This case highlights the highly aggressive nature of FH-dRCC, its propensity for early recurrence and metastasis, and the limited duration of response to current systemic therapies. There is a clinical need for enhanced early detection and active exploration of more effective combination treatment strategies.

Objects To explore the effectiveness and safety of using the Cardio-O-Fix Plug occluder in the treatment of muscular ventricular septal defect(mVSD)in children.Methods 14 patients with mVSD were taken to the cardiology department of First Affiliated Hospital of Kunming Medical University from July 2015 to June 2021 as research subjects.They were divided into two groups:14 children who received Cardi-O-Fix Plug occluder as the experimental group,and 10 children who received Cardi-O-O-Fix mVSD occluder as the control group.Electrocardiogram and transthoracic echocardiography were used to evaluate the occlusive efficacy and incidence of complications 1 day after surgery and 1 month,3 months,and 6 months of follow-up.Results Among the 24 pediatric patients,22 cases were successfully occluded,and 2 cases were unsuccessful(1 in the experi-mental group and 1 in the control group).The success rate of the experimental group was 92.8%(13/14),while the success rate of the control group was 90.0%(9/10).The average surgical duration of the experimental group was(71.93±14.85)minutes,while the average surgical duration of the control group was(90.70±19.78)minutes.There was a significant statistical difference between the two groups(P<0.05).Both the experimental group and the control group did not experience serious complications during surgery and follow-up.There was no significant difference in cardiac ultrasound indicators(including left ventricular ejection fraction,left ventricular end-diastolic diameter,and pulmonary artery pressure)between the two groups at different time points(P>0.05).Conclusion Trans-catheter closure of mVSD using Cardi-O-Fix Plug occluder in children is both safe and effective.The incidence of arrhythmia is low in the short,medium and long term.

Objective: To investigate the impact of temperature changes between neighboring days (TCN) on the mortality risk of respiratory diseases, so as to provide the evidence for the study of deaths from respiratory diseases caused by climate change. Methods: The monitoring data of deaths from respiratory diseases in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance. The meteorological and air pollutant data of the same period were collected from China Meteorological Data Website and ChinaHighAirPollutants dataset. The effect of TCN on the risk of deaths from respiratory diseases was examined using a generalized additive model combined with a distributed lag non-linear model, and subgroup analyses for gender and age were conducted. The disease burden attributed to TCN at different intervals was assessed by calculating attributable fraction. Results: Totally 11 767 deaths from respiratory diseases were reported in Zibo City from 2015 to 2019, including 6 648 males (56.50%) and 5 119 females (43.50%). There were 1 307 deaths aged <65 years (11.11%), and 10 460 deaths aged 65 years and older (88.89%). A monotonically increasing exposure-response relationship was observed between TCN and deaths from respiratory diseases in the general population, females, and the population aged 65 years and older. The 95th percentile of TCN (P95, 3.84 ℃) reached the peak at a cumulative lagged of day 11 (RR=2.063, 95%CI: 1.261-3.376). The results of subgroup analyses showed greater impacts on females and the population aged 65 years and older, with cumulative lagged effects peaking at day 12 (RR=3.119, 95%CI: 1.476-6.589) and day 11 (RR=2.107, 95%CI: 1.260-3.523). The results of attributional risk analysis showed that next-day warming might increase the attributable risk of deaths from respiratory diseases, and next-day cooling might decrease the attributable risk. Conclusion Next-day warming may increase the mortality risk of respiratory diseases, and has greater impacts on females and the population aged 65 years and older.

The syndrome/pattern of defensive qi deficiency is a common basic syndrome of traditional Chinese medicine in clinical practice. However,there is a lack of standardized and operable diagnostic specifications in practical applications. Based on the previous literature,this study proposed the idea of starting from the elements of the syndrome,qualitative diagnostic criteria for the syndrome/pattern of defensive qi deficiency oriented to the entire region of the disease were constructed based on the two dimensions of " deficient defensive qi failing to consolidate the exterior" and " qi deficiency" and constructing a set of quantitative evaluation criteria as the supporting content for the diagnostic items. The core members of the research group attempted to formulate the draft standard,then reached a consensus through the Delphi method expert questionnaire consultation and the Nominal group technique,and finally evaluated the reliability and validity of the standard through clinical verification to provide ideas for the standardization and normalization of research on syndromes.

Muscle-invasive bladder cancer (MIBC) is the predominant type of muscle-invasive urothelial carcinoma (MIUC). MIBC features an unfavorable prognosis with limited treatment approaches. The backbone of treatment strategy was neoadjuvant chemotherapy followed by radical cystectomy before 2021. Immunotherapy represented by nivolumab has gained breakthrough results in adjuvant setting, demonstrating significant improvement in disease free survival in high-risk MIUC population, and become a standard of care for MIUC adjuvant therapy since 2021. Immunotherapy has both efficacy and safety advantages compared to adjuvant chemotherapy. Predictors for adjuvant therapy response in MIUC have yet not been identified. The most evaluated predictive biomarkers to date for immune checkpoint inhibitor treatment response are programmed death ligand 1 (PD-L1) expression and circulating tumour DNA (ctDNA), etc. Further research is crucial to assess the value of the biomarkers. Studies of perioperative immunotherapy combined with chemotherapy or antibody-drug conjugate are ongoing. Combined immunotherapy as part of bladder-sparing treatment regimen for MIUC is limited to small scale studies and has shown promising early outcomes. Further phase 3 clinical trials are underway to add mature data to bladder-sparing strategies incorporating immune checkpoint inhibitors in adjuvant setting.

Muscle-invasive bladder cancer (MIBC) is the predominant type of muscle-invasive urothelial carcinoma (MIUC). MIBC features an unfavorable prognosis with limited treatment approaches. The backbone of treatment strategy was neoadjuvant chemotherapy followed by radical cystectomy before 2021. Immunotherapy represented by nivolumab has gained breakthrough results in adjuvant setting, demonstrating significant improvement in disease free survival in high-risk MIUC population, and become a standard of care for MIUC adjuvant therapy since 2021. Immunotherapy has both efficacy and safety advantages compared to adjuvant chemotherapy. Predictors for adjuvant therapy response in MIUC have yet not been identified. The most evaluated predictive biomarkers to date for immune checkpoint inhibitor treatment response are programmed death ligand 1 (PD-L1) expression and circulating tumour DNA (ctDNA), etc. Further research is crucial to assess the value of the biomarkers. Studies of perioperative immunotherapy combined with chemotherapy or antibody-drug conjugate are ongoing. Combined immunotherapy as part of bladder-sparing treatment regimen for MIUC is limited to small scale studies and has shown promising early outcomes. Further phase 3 clinical trials are underway to add mature data to bladder-sparing strategies incorporating immune checkpoint inhibitors in adjuvant setting.

Objective:To explore the effect of enriched environment on pain sensitivity, anxiety- and depressive-like behavior in selective nerve injury(SNI) rats model and its potential mechanism.Methods:A total of 36 male clean grade SD rats aged 6-8 weeks were randomly divided into three groups( n=12 in each group): sham operation+ standard environment group (sham group), SNI+ standard environment group (standard environment group), SNI+ enriched environment group (enriched environment group). The rat model of neuropathic pain was established by SNI.The rats in the enriched enviroment group were placed in an enriched enviroment 7 days before operation until 21 days after operation.The paw withdraw threshold(PWT) and paw withdraw latency (PWL) were performed to assess hyperalgesia.The open field test, elevated plus maze test, novelty suppressed feeding test and forced swimming test were used to assess anxiety and depression like behavior.The expressions of cAMP response element binding protein (CREB), p-CREB, brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD-95) and neuroligin 2 (NLGN2) were detected by Western blot.The expression of CREB and BDNF in contralateral ACC were measured by immunofluorescence.GraphPad prism 8.0 and SPSS 23.0 were used for data analysis.One way ANOVA was used for inter group comparison, repeated measurement ANOVA was used to analyze PWT and PWL results, and Tukey test was used for pairwise comparison. Results:(1) In PWT and PWL experiments, the interaction effect between group and time, group main effect and time main effect of PWT were significant ( F=13.4, 39.6, 369.6, all P<0.05), and the interaction effect between group and time, group main effect and time main effect of PWL were significant ( F=3.8, 10.3, 58.8, all P<0.05). Compared with sham group, PWT((8.0±3.5) g, (2.4±1.4) g, (2.3±1.1) g, (2.2±1.6) g, (1.6±0.5) g) and PWL((8.6±1.3) s, (7.3±1.5) s, (7.9±1.0) s, (6.6±1.1) s, (7.7±1.4) s) in standard environment group decreased at each time point (all P<0.05). (2) Compared with sham group, the number of entrying into the central area (1.3±1.7), the time of entrying into the central area((1.6±1.3) s), the proportion of entering open arms ((8.0±7.8) %) and the proportion of time in the open arms ((1.3±1.2) %) all significantly decreased in standard environment group ( t=4.585, 5.423, 4.682, 5.202, all P<0.05). The eating latency ((365.2±94.4) s) and immobility time ((127.6±24.3) s) dramatically increased ( t=6.008, 14.290, both P<0.05). The number and time of entrying into central area of enriched environment group were both higher than those of standard environment group(both P<0.05), while the eating latency and immobility time of enriched environment group were both lower than those of standard environment group(both P<0.05). (3) Compared with sham group(CREB: (1.6±0.2), (0.8±0.5); BDNF: (0.8±0.5), (1.0±0.4)), the expression of CREB ((1.8±0.1), (1.5±0.2)), BDNF ((0.9±0.6), (1.4±0.3)) in spinal cord and ACC of standard environment group increased (spinal: t=3.283, 4.989; ACC: t=5.502, 4.257, all P<0.05). The expression of PSD-95 ((1.6±0.2), (1.0±0.2) and NLGN2 ((1.5±0.5), (1.1±0.2)) also increased in ACC of standard enviroment group ( t=4.257, 2.214, both P<0.05). Compared with standard environment group, the expression of CREB (1.3±0.3), BDNF (0.7±0.4), PSD-95(1.0±0.3) and NLGN2(1.1±0.4) in spinal cord of enriched environment group decreased ( t=5.007, 2.166, 2.358, 2.322, all P<0.05). The expression of PSD-95(1.2±0.3) and NLGN2(1.1±0.2) also decreased in ACC of enriched environment group ( t=2.674, 2.944, both P<0.05). However, the expression of p-CREB (1.7±0.6) and BDNF (2.4±0.2) increased in ACC ( t=4.180, 7.610, P<0.05). Conclusion:Enriched environment can improve neuropathic pain and anxiety- and depressive-like behavior in SNI rats, which may be related to the change of synaptic plasticity in spinal cord and ACC.

Objective:To evaluate the effect of dexmedetomidine on pyroptosis in rats with endotoxin-induced acute lung injury (ALI).Methods:Sixty SPF male Sprague-Dawley rats, aged 6 weeks, weighing 200-220 g, were divided into 5 groups ( n=10 each) by a random number table method: control group (group C), ALI group and different doses of dexmedetomidine groups (D 1-3 groups). In ALI group and D 1-3 groups, LPS 5 mg/kg was intraperitoneally injected to establish endotoxin-induced ALI model.Immediately after establishing the model, dexmedetomidine 12.5, 25.0 and 50.0 μg/kg were intraperitoneally injected in D 1-3 groups, and the equal volume of normal saline was intraperitoneally injected in group C, once a day for 14 consecutive days.After the end of administration, the rats were sacrificed, the left bronchus was lavaged, and the left bronchoalveolar lavage fluid (BALF) was collected for determination of the concentrations of interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay), and the lung tissue was taken for determination of the wet/dry weight ratio (W/D ratio) and expression of cleaved-caspase-1, N-terminal of the spliceosome (GSDMD-N), IL-18 and IL-1β (by Western blot) and for microscopic examination of the pathological changes (with a light microscope). Results:Compared with group C, the W/D ratio of lung tissues was significantly increased, the concentrations of IL-1β, IL-6 and TNF-α in BALF were increased, the expression of cleaved-caspase-1, GSDMD-N, IL-1β and IL-18 in lung tissues was up-regulated ( P<0.05), and the pathological damage was aggravated in ALI group and D 1-3 groups.Compared with group ALI, the W/D ratio of lung tissues was significantly decreased, and the concentrations of IL-1β, IL-6 and TNF-α in BALF were decreased, the expression of cleaved-caspase-1, GSDMD-N, IL-1β and IL-18 in lung tissues was down-regulated in a dose-dependent manner ( P<0.05), and the pathological damage was significantly reduced in D 1-3 groups. Conclusion:The mechanism by which dexmedetomidine attenuates endotoxin-induced ALI may be related to inhibition of pyroptosis and reduction of inflammatory responses in rats.

A 69-year old man presented with high-risk metastatic prostate cancer. After 7 months of androgen deprivation therapy (ADT), he progressed to metastatic castration resistant prostate cancer. We suggested him comprehensive therapy, including Abiraterone, chemo-therapy, radio-therapy, platinum chemo-therapy and Enzalutamide, which proved effective with his long term survival.