The present study aimed to explore whether hydrogen sulfide (H₂S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O₂) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N₂ flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H₂S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals ; Rats, Sprague-Dawley ; Male ; Hypertension, Pulmonary/metabolism* ; Glycolysis/drug effects* ; Hydrogen Sulfide/therapeutic use* ; Hypoxia/complications* ; Rats ; Pyroptosis/drug effects*

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

Objective To investigate the diagnostic value of 4 novel inflammatory markers related to routine blood tests,namely neutrophil-to-lymphocyte ratio(NLR),red blood cell distribution width(RDW),hemoglobin-to-RDW ratio(HRR)and systemic immune-inflammation index(SII),in elderly patients with chronic cardiovascular disease(CVD)complicated with frailty.Methods Retrospectively analyze 110 patients with chronic stable CVD who were hospitalized in the cadre ward of cardiovascular medicine at the Air Force Characteristic Medical Center from January 2022 to June 2023.According to the assessment results of the Fried scale,they were divided into three groups:non-frailty group(Fried score=0,n=30),the pre-frailty group(Fried score 1 or 2,n=40)and frailty group(Fried score≥3,n=40).The differences in general information,the impairment rate of daily living activities,miniature nutritional assessment-short form(MNA-SF)scores,mini-mental state examination(MMSE)scores,and the indicators such as NLR,RDW,HRR,and SII among the three groups were compared.Spearman rank correlation was used to analyze the correlation between NLR,RDW,HRR,SII and frailty scores as well as each frailty indicator.Multivariate logistic regression analysis was performed to identify the independent risk factors for frailty in elderly patients with chronic CVD,and the receiver operating characteristic(ROC)curve was used to assess the clinical diagnostic value of NLR and HRR in elderly patients with chronic CVD complicated with frailty.Results Compared with non-frailty group and pre-frailty group,patients in frailty group were older,with higher impaired rates of daily living activities,NLR,RDW,and SII,and lower MNA-SF scores,MMSE scores,and HRR,and differences were statistically significant(P<0.05).Spearman rank correlation analysis showed that the frailty score was positively correlated with NLR(rs=0.354,P<0.001),and RDW(rs=0.448,P<0.001),negatively correlated with HRR(rs=-0.232,P=0.024),and had no significant correlation with SII(rs=0.144,P=0.167).Further analysis of the correlation between the above novel inflammatory markers and the 5 components of frailty showed that NLR was positively correlated with fatigue(rs=0.228,P=0.017),slowed walking speed(rs=0.299,P<0.001),and low physical function(rs=0.319,P<0.001);RDW was positively correlated with decreased grip strength(rs=0.321,P<0.001),slowed walking speed(rs=0.422,P<0.001),and low physical function(rs=0.246,P=0.001);and HRR was negatively correlated with slowed walking speed(rs=-0.230,P=0.025),and low physical function(rs=-0.299,P=0.003).Multivariate logistic regression analysis showed that MNA-SF score(OR=0.577,95%CI 0.342-0.973)was an independent protective factor for pre-frailty in elderly patients with chronic CVD(P<0.05);NLR(OR=7.866,95%CI 1.101-56.185)was an independent risk factor for frailty,while HRR(OR=0.344,95%CI 0.120-0.983)and MNA-SF score(OR=0.292,95%CI 0.146-0.580)were independent protective factors for frailty in elderly CVD patients(P<0.05).The area under the ROC curve of NLR and HRR for diagnosing frailty in elderly patients with chronic CVD were 0.778 and 0.749,respectively.Conclusion NLR and HRR have high clinical diagnostic value for frailty in elderly patients with chronic CVD,and are expected to become effective inflammatory markers for screening elderly patients with chronic CVD complicated with frailty.

ObjectiveTo analyze the clinical characteristics and the use of traditional Chinese medicine （TCM） therapy in cancer patients with COVID-19， and to provide reference for making TCM prevention and treatment strategies and determining diagnosis and treatment priorities for patients with malignant tumors in the COVID-19 epidemic. MethodsThe medical records of 225 malignant tumor cases with COVID-19 who were admitted to 7 national research centers from January 1st to 20th， 2023 were retrospectively collected， and the main symptoms and duration after infection， nucleic acid negative conversion time， use of TCM therapy， and changes in adverse reactions after resuming anti-tumor treatment were analyzed. ResultsA total of 222 malignant tumor patients with COVID-19 were included in the analysis， involving 205 mild cases and 17 moderate cases. The top four most frequently reported clinical symptoms were fever （165 cases）， expectoration or dry cough （99 cases）， decreased appetite （95 cases） and fatigue （85 cases）， of which 40 expectoration or dry cough cases ， 37 fatigue cases and 29 decreased appetite cases lasted for more than 14 days. One hundred and five patients with nucleic acid detection report had a median negative conversion time of 14 days. The nucleic acid negative conversion time was significantly longer in patients with lung cancer compared to those with digestive system malignant tumors， and in those with myelosuppression than those without （P＜0.01）. During the infection period， 47.30% （105/222） of the patients used Chinese patent medicine， and 21.17% （47/222） were treated with herbal decoctions. The use of TCM in patients during the prevention and rehabilitation period， was 1.80%（4/222） and 7.21%（16/222）， respectively. Fifty-five patients resumed anti-tumor treatment after nucleic acid negative conversion， and received TCM simultaneously. Observed adverse reactions， including gastrointestinal reactions， bone marrow suppression， and neurotoxicity， were all grade 1 to 2， and no new adverse events occurred during follow-up. ConclusionCertain malignant tumor patients with COVID-19 had prolonged symptoms and nucleic acid negative conversion time Rational use of TCM can help to promote the rehabilitation of the patients and ensure the smooth process of anti-tumor treatment after infection.

Objective:To establish a prediction model for symptomatic radiation pneumonitis (SRP) after radiotherapy for thoracic cancer based on a longitudinal cohort and dose interval variations.Methods:Clinical data of 587 patients who received thoracic radiotherapy in Department of Radiotherapy of Yunnan Cancer Hospital from July 2022 to June 2023 were retrospectively analyzed. The National Cancer Institute common terminology criteria for adverse events (CTCAE) version 5.0 was used to grade radiation pneumonitis, and clinical factors, traditional independent dosimetric characteristics and dose interval variation characteristics were collected. Features used to predict the occurrence of SRP were screened using genetic algorithms and analyzed the correlation between the selected features and SRP occurrence. Predictive models for SRP occurrence were established using the selected features and evaluated, and the optimal predictive model was visualized using a column chart.Results:The incidence of SRP was 35.94%. Five clinical factors, seven independent dosimetric features and six dose interval variation features were screened out by genetic algorithms to effectively predict the occurrence of SRP. The area under ROC curve (AUC) of clinical factors combined with traditional independent dosimetric factors and dose interval variation factors was 76%. The AUC of clinical factors combined with traditional independent dosimetric factors and that of clinical factors combined with dose interval variation factors was 69% and 67%, respectively. The addition of the characteristics of dose interval variation factors significantly improved the effectiveness of the prediction model.Conclusions:The supplement of the characteristics of dose interval variation factors can significantly improve the performance of the SRP prediction model for thoracic tumors after radiotherapy. The SRP prediction model based on dose interval variations can effectively predict the occurrence of SRP.

Etomidate reversibly blocks 11-β-hydroxylated steroid dehydrogenase inhibits the synthesis of cortisol by adrenal cells.This product is a special injection.When evaluating the quality and efficacy of the generic and the reference preparations,it should be based on pharmaceutical and non-clinical consistency and adopt a step-by-step research strategy,firstly,bioequivalence(BE)was studied.In bioequivalence study,the research type,dosage and method,bioequivalence evaluation,safety monitoring and pharmacodynamics(PD)evaluation should be considered and designed reasonably.Based on the pharmacokinetics(PK)characteristics of etomidate medium-long chain fat emulsion injection and the bioequivalence study of its generic drug before its domestic market,the general design requirements and relevant considerations for the bioequivalence study of this product were systematically discussed.The purpose is to provide useful reference and guidance for domestic research and development of generic drugs.

Background::Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods::Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.Results::A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04–13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65–3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38–1.53; P <0.001). Conclusions::In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration::ClinicalTrials.gov, NCT02309398.

Objective To develop a portable collection device of human exhaled breath condensate(EBC)based on natural breathing to meet the needs for rapid screening of human respiratory tract(especially lower respiratory tract)infections.Methods The device consisted of a refrigeration unit,a heat dissipation unit and a condensation unit.The refrigeration unit adopted a TES1-7102 thermoelectric Peltier cooler semiconductor as the refrigeration element;the heat dissipation unit was composed of a high thermal conductivity aluminum heat sink and a high-speed brushless cooling fan;the condensation unit was made up of a cold guide plate and a condenser,in which the cold guide plate was made of thin sheet of aluminum alloy,and the condenser was prepared by 3D printing technology and made of hydrophobic polylactic acid,with primary and secondary 2-stage guide grooves and an ultra-thin condensing surface.The performance of the device was verified in terms of cooling,thermal conductivity,condensation and human EBC collection and content analysis.Results Performance analysis showed that after refrigeration began the temperature difference between the condenser surface and the exhaled gas met the requirements of the condenser,and no obvious thermal resistance was found on the condensing surface so that large droplets could be formed rapidly and then be collected after the gas-liquid phase change of the exhaled gas on the condensing surface.Human EBC collection and content analysis indicated the device realized home self-collection of EBCs from people of all ages,and the concentrations of interleukins,C-reactive protein and other inflammation-related indexes and the pH value of the collected EBC samples were all correlated with respiratory infections in the subjects.Conclusion The device developed with easy operation avoids the discomfort of blowing collection and the risk of saliva contamination,and is worthy promoting for rapid diagnosis and dynamic monitoring of respiratory tract infection and other related diseases.[Chinese Medical Equipment Journal,2024,45(8):32-37]

Objective To explore the effect of a multiple heat-preservation approach during the peri-operative period of hip arthroscopy on core body temperature,anesthesia recovery time and postopera-tive shivering.Methods Eighty patients who underwent arthroscopic acetabular labral repair between Jan-uary 2020 and June 2021 were selected and randomly divided into a control group and an observation group,each of 40.During the perioperative period,both groups received routine nursing,while the ob-servation group was additionally provided with a series of heat-preservation measures including raising the room temperature,liquid heating and warm blanket insulation.The core body temperature was mon-itored by an axillary probe.Moreover,the perioperative core body temperature,anesthesia recovery time,and incidence of postoperative shivering were compared between the two groups.Results There was no significant differences were found between the two groups in the preoperative core body temper-ature(P>0.05).However,the core body temperature of the observation group was significantly higher than the control group intraoperatively(36.2℃±0.2℃vs 35.9℃±0.2℃,P<0.001)and postoperatively(36.6℃±0.2℃vs 36.4℃±0.2℃,P<0.001),while the incidence of intraoperative hypothermia(<36.0℃)of the observation group was significantly lower than the latter(7.5%vs 70.0%,P<0.001).Meanwhile,the anesthesia recovery time[27.0(24.0,30.0)min vs 30.0(28.0,33.0)min,M(P25,P75),P<0.001]and incidence of postoperative shivering(7.5%vs 25.0%,P=0.034)in the observation group were significantly lower than the control group.Conclusion Adopting a multiple heat-preservation approach during the perioperative period of hip arthroscopy can help maintain the core body tempera-ture,shorten the anesthesia recovery time,and reduce the incidence of postoperative shivering.

Objective To observe the preventive effect of early comfort using analgesia, minimal sedatives and maximal humane care (eCASH)concept on delirium in patients in coronary care unit(CCU). Methods The clinical data of 136 CCU patients admitted from June 2021 to January 2023 were retrospectively analyzed. Patients received routine delirium prevention care from June 2021 to March 2022 were included in control group (n=69), and patients received eCASH philosophy care from April 2022 to January 2023 were included in observation group (n=67). Delirium prevention effect, condition of restlessness and sedation, CCU length of stay and cognitive function were compared between the two groups. Results The incidence of delirium in the observation group was 4.48%, which was significantly lower than 17.39% in the control group (P < 0.05). The duration of delirium and CCU length of stay in the observation group were significantly shorter than those in the control group (P < 0.05). After intervention, the scores of Richmond Agitation and Sedation Scale (RASS) and Montreal Cognitive Assessment Scale (MoCA) were significantly higher in the two groups than before intervention, and the observation group was significantly higher than the control group (P < 0.05). The average dose of analgesic and sedative drugs (propofol and regal) in the observation group was significantly lower than that in the control group (P < 0.05). Conclusion The analgesic and sedative control scheme based on eCASH concept can reduce the incidence of delirium, shorten the duration of delirium and hospital stay, and improve the agitation sedation and cognitive function of CCU patients.