ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula （MQEF） in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS），network pharmacology， and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B （UVB）. The safe doses of bakuchiol （BAK） and salvianolic acid B （SAB） for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 （CCK-8） method.The reactive oxygen species （ROS） fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress，inflammation，collagen metabolism，and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified，which acted on 367 potential targets，and 417 targets related to skin photoaging were screened out，among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB，which acted on core proteins such as serine/threonine kinase 1 （Akt1） and mitogen-activated protein kinase 3 （MAPK3） and intervened in core pathways such as the tumor necrosis factor （TNF） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathways.Compared with the model group，the administration of BAK and SAB increased the survival rate of HaCaT cells （P<0.01），down-regulated the mRNA levels of cyclooxygenase-2 （COX-2），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），matrix metalloproteinase-1 （MMP-1），and matrix metalloproteinase-9 （MMP-9） （P<0.01），and up-regulated the mRNA levels of heme oxygenase-1 （HO-1） and NAD（P）H quinone dehydrogenase 1 （NQO-1） （P<0.05，P<0.01） in photoaged HaCaT cells.In addition，it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 （BMAL1） and circadian locomotor output cycles kaput （CLOCK） associated with circadian clock （P<0.05，P<0.01）. ConclusionMQEF delays skin photoaging through the coordinated effects of various components，multiple targets，and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties，which involve inhibiting oxidative stress，preventing collagen degradation，mitigating inflammation，and maintaining normal skin circadian rhythms by regulating clock gene expression.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

OBJECTIVE: To explore the implementation effect of hour-1 bundle for sepsis patients based on crisis resource management (CRM) system. METHODS: A historical control study was conducted. The hour-1 bundle for sepsis based on CRM was used to train 24 nurses in the emergency department from October 2022 to March 2023. Clinical data of sepsis patients admitted to the emergency department of the First People's Hospital of Zunyi from April 2022 to September 2023 were collected. The patients were divided into three groups based on different stages of CRM system construction: control group (before construction, from April to September in 2022), improvement group (during construction, from October 2022 to March 2023) and observation group (after construction, from April to September in 2023). The baseline data, implementation rate of hour-1 bundle [including blood culture, antibiotic usage, blood lactic acid (Lac) detection, fluid resuscitation, hypertensors usage], identification and diagnosis time, and prognosis parameters [including correction rate of hypoxemia, intensive care unit (ICU) occupancy rate, and 28-day survival rate]. Sepsis cognition survey and non-technical skill (NTS) evaluation of nurses in emergency department were conducted before and after training. RESULTS: Finally 43 cases were enrolled in the control group, improvement group and observation group, respectively. There was no statistically significant difference in baseline data including the gender, age, primary site, heart rate, systolic blood pressure, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, mechanical ventilation ratio among the three groups with comparability. With the gradual improvement of the CRM system, the implementation rate of 1-hour bundle was gradually increased, and the implementation rate in the control group, improvement group and observation group were 65.12% (28/43), 74.42% (32/43) and 88.37% (38/43), respectively, with statistically significant difference (P < 0.05). It was mainly reflected in the completion rate of blood culture, antibiotic usage rate, Lac detection rate and hypertensors usage rate within 1 hour, which were significantly higher in the observation group than those in the control group [completion rate of blood culture: 90.70% (39/43) vs. 62.79% (27/43), antibiotic usage rate: 88.37% (38/43) vs. 60.47% (26/43), Lac detection rate: 93.02% (40/43) vs. 72.09% (31/43), hypertensors usage rate: 88.37% (38/43) vs. 60.47% (26/43), all P < 0.05]. The fluid resuscitation rates within 1 hour in the three groups were all over 90%, with no statistically significant difference among the three groups. The recognition and diagnosis time in the observation group was significantly shorter than that in the control group and the improvement group (hours: 0.41±0.15 vs. 0.61±0.21, 0.51±0.18, both P < 0.05), the correction rate of hypoxemia and 28-day survival rate were significantly higher than those in the control group [correction rate of hypoxemia: 95.35% (41/43) vs. 74.42% (32/43), 28-day survival rate: 83.72% (36/43) vs. 60.47% (26/43), both P < 0.05], and ICU occupancy rate was significantly lower than that in the control group [72.09% (31/43) vs. 93.02% (40/43), P < 0.05]. After training in the CRM system, the score of the sepsis awareness survey questionnaire for emergency department nurses was significantly increased as compared with before training (60.42±5.29 vs. 44.17±9.21, P < 0.01), and NTS also showed significant improvement. CONCLUSION CRM plays a significant role in promoting the implementation of sepsis hour-1 bundle, which can improve the implementation rate of hour-1 bundle and NTS of medical staff, effectively improve patients' hypoxemia, reduce patients' ICU occupancy rate and 28-day risk of death.
Humans ; Sepsis/therapy* ; Emergency Service, Hospital ; Patient Care Bundles ; Intensive Care Units ; Female ; Male ; Middle Aged

Objective:To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated with pancreatogenic portal hypertension (PPH) and to establish a prediction model.Methods:From January 1, 2016 to December 31, 2022, a total of 1 095 patients diagnosed with MSAP or SAP at the First Affiliated Hospital of Kunming Medical University were enrolled and divided into PPH group (145 cases) and non-PPH group (950 cases) according to the presence or absence of concomitant PPH. The general data (gender, etiology of acute pancreatitis, days of hospitalization, etc.), complications (portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, etc.), laboratory indicators (albumin, D-dimer, etc.), and scores of modified computed tomography severity index (MCTSI) were collected in the two groups. The least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression analysis were performed to analyze the independent risk factors of MSAP and SAP complicated with PPH, and the nomogram prediction model was established. The area under the curve of the receiver operating characteristic curve was calculated to evaluate the discrimination of the calibration curve and Hosmer-Lemeshow goodness of fit test were used to assess the predictive accuracy of the model, and clinical decision curve analysis (DCA) was used to evaluate the clinical practicability of the model.Results:The results of LASSO and multivariate logistic regression analysis showed that portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin were independent risk factors of MSAP and SAP complicated with PPH ( OR=7.013, 2.085, 1.846, 1.030, 1.235 and 0.955; 95% confidence interval 4.061 to 12.112, 1.255 to 3.463, 1.066 to 3.199, 1.013 to 1.047, 1.123 to 1.357 and 0.927 to 0.983; all P<0.05). The area under the curve of the model was 0.820 (95% confidence interval 0.780 to 0.859), the calibration curve was close to the reference curve, and the Hosmer-Lemeshow goodness-fit test showed that the model had a good fit ( χ2=9.82, P=0.278). The result of DCA indicated that the model had a high net benefit in a wide range of risk threshold (threshold probability 0.1 to 0.9), and had certain clinical practicability. Conclusions:Portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin are the independent risk factors of MSAP and SAP complicated with PPH. The established nomogram model has good differentiation, calibration and clinical practicability.

Objective:To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated with pancreatogenic portal hypertension (PPH) and to establish a prediction model.Methods:From January 1, 2016 to December 31, 2022, a total of 1 095 patients diagnosed with MSAP or SAP at the First Affiliated Hospital of Kunming Medical University were enrolled and divided into PPH group (145 cases) and non-PPH group (950 cases) according to the presence or absence of concomitant PPH. The general data (gender, etiology of acute pancreatitis, days of hospitalization, etc.), complications (portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, etc.), laboratory indicators (albumin, D-dimer, etc.), and scores of modified computed tomography severity index (MCTSI) were collected in the two groups. The least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression analysis were performed to analyze the independent risk factors of MSAP and SAP complicated with PPH, and the nomogram prediction model was established. The area under the curve of the receiver operating characteristic curve was calculated to evaluate the discrimination of the calibration curve and Hosmer-Lemeshow goodness of fit test were used to assess the predictive accuracy of the model, and clinical decision curve analysis (DCA) was used to evaluate the clinical practicability of the model.Results:The results of LASSO and multivariate logistic regression analysis showed that portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin were independent risk factors of MSAP and SAP complicated with PPH ( OR=7.013, 2.085, 1.846, 1.030, 1.235 and 0.955; 95% confidence interval 4.061 to 12.112, 1.255 to 3.463, 1.066 to 3.199, 1.013 to 1.047, 1.123 to 1.357 and 0.927 to 0.983; all P<0.05). The area under the curve of the model was 0.820 (95% confidence interval 0.780 to 0.859), the calibration curve was close to the reference curve, and the Hosmer-Lemeshow goodness-fit test showed that the model had a good fit ( χ2=9.82, P=0.278). The result of DCA indicated that the model had a high net benefit in a wide range of risk threshold (threshold probability 0.1 to 0.9), and had certain clinical practicability. Conclusions:Portal vein thrombosis, pancreatic pseudocyst, pancreatic encapsulated necrosis, days of hospitalization, MCTSI and decreased albumin are the independent risk factors of MSAP and SAP complicated with PPH. The established nomogram model has good differentiation, calibration and clinical practicability.

Objective:To compare the performance of four ELISA kits for detecting measles virus IgG antibody and to provide support for sero-epidemiologic survey.Methods:A total of 176 specimens were tested by four ELISA kits, respectively. The result of 4 kits were analyzed by the McNemar’s test. The values such as Kappa value, CV value, sensitivity, specificity, positive predictive value and negative predictive values were calculated and compared.Results:There was no significant difference among the result from kits and references, the χ2 were 0.333, 2.000, 1.000 and 0 respectively. The Kappa value of kit C was the highest (0.976), the sensitivity of kit A, C and D were the highest (99.34%), the specificity of kit B and C were the highest (100%), the positive predictive value of kit B and C were the highest (100%) and the negative predictive value of kit C were the highest (96.00%), there was no significant difference among the indicators from 4 kits ( P >0.05). The CV value of kit D was the lowest (5.30%). The correlation coefficient between the result from kit C and D was 0.639 ( P<0.01). Conclusions:The result showed that the 4 kits were suitable for serum epidemiologic survey.

Objective To explore the etiology and clinical characteristics of short stature. Method Clinical data of 2075 children with short stature treated from May 1995 to July 2017 were retrospectively analyzed. The etiology and morbidity of pathological short stature and normal variant short stature were analyzed. The clinical characteristics of growth hormone deficiency (GHD) , idiopathic short stature (ISS) , constitutional delay in growth (CDG) and familial short stature (FSS) were analyzed. The etiological differences between severe short stature [height standard deviation score (SDS) ≤-3] and general short stature (height SDS＞-3) were analyzed. Results Among 2075 children diagnosed with short stature, 1719 (82.84％) were pathological short stature, among which GHD (38.60％) and ISS (22.02％) were more common. Normal variant short stature was found in 356 children (17.16％) , with FSS and CDG accounting for 10.70％ and 6.46％ respectively. There were statistically significant differences in the sex ratio, age at initial diagnosis, height SDS, body mass index (BMI) , bone age and bone age delay among children with four common childhood short stature (GHD, ISS, CDG and FSS) (all P＜0.01) . Boys were more than girls in four kinds of childhood short stature. The height SDS was the lowest in GHD group and the highest in CDG group; BMI was highest in GHD group, but lower in CDG and ISS group. Bone age delay was highest in GHD group and lowest in CDG group. In severe short stature group, the rates of complete GHD, multiple pituitary hormone deficiency, small for gestational age infant, Turner syndrome, hypothyroidism and Russell-Silver syndrome were higher than those in general short stature group, but the rates of partial GHD, ISS, FSS and CDG was lower than those in general short stature group. Conclusion The etiology of short stature is complex. Analysis of the etiology and clinical features is helpful for clinical diagnosis and treatment.

Objective To understand the rationality and safety of oral antihypertensive drugs on chronic renal disease(CKD)combined with hypertension hospitalized patients. Methods It was a multi-center and retrospective investigation. The electronic medical records of CKD with hypertension patients who were hospitalized in 6 comprehensive hospitals in Beijing and used oral antihypertensive drugs on October 1st,2013 to March 31st,2015 were collected. The pharmacists who participated in the project from the 6 research centers filled out the investigation form. According to the drug instruction,the rationality of antihypertensive medication was evaluated by daily dose,frequency of drug delivery,the dosage for renal insufficiency,contraindications and adverse interactions. Results There were 2 833 valid cases in this study,1 730 males and 1 103 females. The ratio of male to female was 1:0.64. The range of age was 18~101 years. The average age was(61 ± 18)years. There were 1 630(57.54%)cases whose age was≥60;314(11.1%)cases were CKD level 1,526(18.6%)cases were CKD level 2,1 117(39.4%)cases were CKD level 3,423(14.9%)cases were CKD level 4,453(16.0%)cases were CKD level 5. 144 (5.1%)cases were hypertension level 1,592(20.9%)cases were hypertension level 2,1 398 cases (49.3%)were hypertension level 3,and 699(24.7%)cases were not graded. The oral hypotensive drugs applied during the hospitalization of 2 833 patients included calcium channel blockers(CCB),beta blockers,diuretics,angiotensin Ⅱ receptor blocker(ARB),angiotensin converting enzyme inhibitors (ACEI),alpha/beta blockers and alpha blockers. 1 022(36.1%)cases used 1 kind of antihypertensive drugs,1 032(36.4%)cases used 2 kinds of antihypertensive drugs,591(20.9%)cases used 3 kinds of antihyper-tensive drugs,157(5.5%)cases used 4 kinds of antihypertensive drugs and 31(1.1%)cases used 5 kinds of antihypertensive drugs. A total of 6038 cases of antihypertensive drugs were administered. The top priority was CCB(35.11%,2 120),the second was beta blockers(17.26%,1 042)and the third was diuretics(16.23%,980). The choice of a single drug for antihypertensive drugs was reasonable. The 2,3,4,5 combined drug users who were not recommended by the guidelines were 4.8%(50/1 032), 21.2%(125/591),28.0%(44/157)and 64.5%(20/31)respectively. The situation of blood pressure control was evaluated with blood pressure target values achieved rate. With blood pressure below 130/80 mmHg as the standard,the admission and discharge blood pressure target achieved rate was 31.2%(884/2 833)and 29.5%(799/2 705)respectively. With blood pressure below 140/90 mmHg as the standard, the admission and discharge blood pressure target achievement rate was 53.6%(1 519/2 833)and 64.4%(1 743/2 705)respectively. Among the 2 833 cases,903(31.9%)cases had 1 204 times of unreasonable use of the drug. The top three were excessive daily frequency of medication(1 029,85.5%),total daily dosage(114,9.5%),and use of drugs that were contraindicated(51,4.2%). Two cases had adverse drug reactions related to antihypertensive drugs. Conclusion The use of antihypertensive drugs in patients with CKD in the six hospitals involved in the investigation was reasonable,but there was still some problems in the combination of drugs. Some doctors are not familiar with the drug instructions,and there are some problems such as increasing the frequency of drug use,overdose medication,and use of drugs that are contraindicated. Clinical pharmacists should be more involved in clinical work in these areas.

Objective To understand the rationality and safety of oral antihypertensive drugs on chronic renal disease(CKD)combined with hypertension hospitalized patients. Methods It was a multi-center and retrospective investigation. The electronic medical records of CKD with hypertension patients who were hospitalized in 6 comprehensive hospitals in Beijing and used oral antihypertensive drugs on October 1st,2013 to March 31st,2015 were collected. The pharmacists who participated in the project from the 6 research centers filled out the investigation form. According to the drug instruction,the rationality of antihypertensive medication was evaluated by daily dose,frequency of drug delivery,the dosage for renal insufficiency,contraindications and adverse interactions. Results There were 2 833 valid cases in this study,1 730 males and 1 103 females. The ratio of male to female was 1:0.64. The range of age was 18~101 years. The average age was(61 ± 18)years. There were 1 630(57.54%)cases whose age was≥60;314(11.1%)cases were CKD level 1,526(18.6%)cases were CKD level 2,1 117(39.4%)cases were CKD level 3,423(14.9%)cases were CKD level 4,453(16.0%)cases were CKD level 5. 144 (5.1%)cases were hypertension level 1,592(20.9%)cases were hypertension level 2,1 398 cases (49.3%)were hypertension level 3,and 699(24.7%)cases were not graded. The oral hypotensive drugs applied during the hospitalization of 2 833 patients included calcium channel blockers(CCB),beta blockers,diuretics,angiotensin Ⅱ receptor blocker(ARB),angiotensin converting enzyme inhibitors (ACEI),alpha/beta blockers and alpha blockers. 1 022(36.1%)cases used 1 kind of antihypertensive drugs,1 032(36.4%)cases used 2 kinds of antihypertensive drugs,591(20.9%)cases used 3 kinds of antihyper-tensive drugs,157(5.5%)cases used 4 kinds of antihypertensive drugs and 31(1.1%)cases used 5 kinds of antihypertensive drugs. A total of 6038 cases of antihypertensive drugs were administered. The top priority was CCB(35.11%,2 120),the second was beta blockers(17.26%,1 042)and the third was diuretics(16.23%,980). The choice of a single drug for antihypertensive drugs was reasonable. The 2,3,4,5 combined drug users who were not recommended by the guidelines were 4.8%(50/1 032), 21.2%(125/591),28.0%(44/157)and 64.5%(20/31)respectively. The situation of blood pressure control was evaluated with blood pressure target values achieved rate. With blood pressure below 130/80 mmHg as the standard,the admission and discharge blood pressure target achieved rate was 31.2%(884/2 833)and 29.5%(799/2 705)respectively. With blood pressure below 140/90 mmHg as the standard, the admission and discharge blood pressure target achievement rate was 53.6%(1 519/2 833)and 64.4%(1 743/2 705)respectively. Among the 2 833 cases,903(31.9%)cases had 1 204 times of unreasonable use of the drug. The top three were excessive daily frequency of medication(1 029,85.5%),total daily dosage(114,9.5%),and use of drugs that were contraindicated(51,4.2%). Two cases had adverse drug reactions related to antihypertensive drugs. Conclusion The use of antihypertensive drugs in patients with CKD in the six hospitals involved in the investigation was reasonable,but there was still some problems in the combination of drugs. Some doctors are not familiar with the drug instructions,and there are some problems such as increasing the frequency of drug use,overdose medication,and use of drugs that are contraindicated. Clinical pharmacists should be more involved in clinical work in these areas.