Objective:To investigate the clinical efficacy and safety of non-invasive bilevel positive airway pressure (BiPAP) ventilator combined with oxygen atomization in the treatment of chronic obstructive pulmonary disease (COPD) complicated with type Ⅱ respiratory failure.Methods:A total of 80 patients with COPD complicated with type Ⅱ respiratory failure admitted to Haiyan County People′s Hospital from June 2019 to July 2021 were selected, and they were divided into the observation group and the control group by the random number table method, with 40 cases in each group. Patients in both groups received conventional treatment, while patients in the control group were connected with BiPAP non-invasive ventilator and received non-invasive mechanical ventilation in S/T mode; the observation group was given aerosol inhalation drugs during ventilation, and both groups were treated for 7 d. Blood gas indicators and vital signs were collected before treatment and 7 d after treatment. Clinical symptoms were investigated by COPD patient Caring Assessment Tool (CAT) and Dyspnea Scale (DECAF). Serum levels of interleukin (IL)-10, tumor necrosis factor (TNF-α) and CD 4+/CD 8+ were determined, and treatment outcomes and adverse reactions were compared between the two groups. Results:After treatment, the partial pressure of oxygen (PaO 2) and the oxygen saturation (SaO 2) in the observation group were higher than those in the control group: (73.41 ± 5.26) mmHg(1 mmHg = 0.133 kPa) vs. (65.11 ± 4.33) mmHg, 0.921 ± 0.052 vs. 0.884 ± 0.039; the arterial partial pressure of carbon dioxide (PaCO 2), heart rate (HR), respiratory rate (RR) were lower than those in the control group: (45.20 ± 5.33) mmHg vs. (50.52 ± 5.96) mmHg, (90.12 ± 8.56) times/min vs. (98.52 ± 9.63) times/min, (17.41 ± 2.26) times/min vs. (22.10 ± 3.05) times/min, there were statistical differences ( P<0.05). After treatment, CAT scores and DECAF scores in the observation group were lower than those in the control group: (8.45 ± 1.63) scores vs. (12.77 ± 2.36) scores, (0.89 ± 0.15) scores vs. (1.15 ± 0.19) scores, there were statistical differences ( P<0.05). After treatment, the levels of IL-10 and CD 4+/CD 8+ in the observation group were higher than those in the control group: (15.28 ± 3.12) ng/L vs. (13.41 ± 2.96) ng/L, 1.71 ± 0.38 vs. 1.54 ± 0.30; while the level of TNF-α was lower than that in the control group: (215.27 ± 33.96) ng/L vs. (251.11 ± 50.95) ng/L, there were statistical differences ( P<0.05). The hospitalization time in the observation group was shorter than that in the control group: (13.52 ± 3.96) d vs. (15.22 ± 2.74) d, there was statistical difference ( P<0.05). The rates of tracheal intubation and the incidence of adverse reactions between the two groups had no significant differences ( P>0.05). Conclusions:Non-invasive BiPAP ventilator combined with oxygen atomization can improve blood gas index, vital signs and clinical symptoms of COPD patients complicated with type Ⅱ respiratory failure and reduce inflammatory response.

Objective:To evaluate the interaction between remimazolam and propofol for sedation during hysteroscopy.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 20-45 yr, with body mass index of 18-28 kg/m 2, scheduled for elective hysteroscopy, were included. The test was conducted in two steps. Up-and-down sequential allocation was used to determine the median effective dose (ED 50) of remimazolam (group A) and propofol (group B). The ED 50 obtained in A and B groups were then used as the standard to determine the combination regimen in group C (0.25×ED 50 of remimazolam+ 0.75×ED 50 of propofol as the initial dose), in group D (0.5×ED 50 of remimazolam+ 0.5×ED 50 of propofol as the initial dose), and in group E (0.75×ED 50 of remimazolam+ 0.25×ED 50 of propofol as the initial dose). Up-and-down sequential allocation was used to determine the ED 50 of propofol when propofol and remimazolam were combined in C, D and E groups. The interaction between the sedative effects of two drugs was analyzed using the isobolographic analysis method, and the interaction coefficient and synergistic dose ratio of two drugs were calculated. Results:The ED 50 of remimazolam was 0.180 mg/kg in group A, and the ED 50 of propofol was 1.167 mg/kg in group B. The results of isobolographic analysis showed that remimazolam and propofol had a synergistic effect. When remimazolam 0.045, 0.090 and 0.135 mg/kg were combined with propofol 0.546, 0.288 and 0.160 mg/kg, the interaction coefficients were 1.393, 1.339 and 1.127 respectively. The synergistic dosage ratio of remimazolam and propofol was 1.0∶(3.2 to 12.0). Conclusions:Remimazolam and propofol have a synergistic effect on sedation when used for hysteroscopy, and the dose ratio is 1.0∶(3.2-12.0).

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

SGLT2 inhibitors currently have clear benefits in the treatment of heart failure whether combined with diabetes or not. Ventricular remodeling after myocardial infarction leads to the occurrence and development of heart failure, and eventually leads to death. There are relatively few studies on SGLT2 inhibitors in patients with myocardial infarction. The purpose of this article is to review the research progress of SGLT2 inhibitors application before and after myocardial infarction.

ObjectiveTo investigate the effectiveness and safety of nanoknife ablation guided by real-time virtual sonography (RVS) in the treatment of locally advanced pancreatic cancer (LAPC). MethodsA retrospective analysis was performed for the clinical data of 27 patients with LAPC who attended The Fifth Affiliated Hospital of Zhengzhou University from April 2018 to October 2019, and according to the treatment method, the patients were divided into combination group (12 patients treated with IRE combined with chemotherapy) and control group (15 patients treated with chemotherapy alone). The chemotherapy regimen was gemcitabine combined with tegafur, gimeracil and oteracil potassium for both groups. Adverse reactions and complications were observed for the combination group during the perioperative period, and the two groups were compared in terms of the changes in myocardial enzymes, blood amylase, and carbohydrate antigen 19-9 (CA19-9) before treatment and at different time points after treatment, as well as remission rate (RR) and disease control rate (DCR) at 3 months after treatment and survival status during follow-up. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the Wilcoxon test was used for comparison within each group; the Fisher’s exact test was used for comparison of categorical data between groups; the Kaplan-Meier method was used to analyze the survival status during follow-up. ResultsIn the combination group, there were 12 cases of adverse reactions and mild complications during the perioperative period, i.e., 9 Clavien-Dindo grade I cases and 3 grade II cases. All patients in the combination group experienced a transient increase in myocardial enzymes, which returned to normal within 7 days, and there were no significant changes in creatine kinase and lactate dehydrogenase on day 7 after treatment (P＞0.05); 9 patients had a significant increase in blood amylase on day 1 after surgery, which significantly decreased on day 7 after surgery and basically returned to normal on day 14 after surgery, and there was no significant change in blood amylase on days 7、14， and 1 month after surgery (P＞0.05). Before treatment, the level of CA19-9 was higher than the normal value in both groups, and the combination group had a significant reduction in CA19-9 at 1, 2, and 3 months after treatment (all P＜005); in the control group, the level of CA19-9 firstly decreased for a short time and then increased, while there was no significant change in CA19-9 at 1, 2, and 3 months after treatment (all P＞0.05). At 3 months after treatment, the combination group had significantly higher RR and DCR than the control group (RR: 75.0% vs 26.7%, P=0.021; DCR: 91.6% vs 53.3%, P=0043). During the median follow-up time of 13 months, compared with the control group, the combination group had significantly higher median progression-free survival time (10 months vs 5 months, P=0.014) and median overall survival time (18 months vs 10 months, P=0.034). ConclusionRVS-guided percutaneous nanoknife ablation has marked clinical effect and high safety in the treatment of LAPC and can be used as a new treatment option for patients who refuse or cannot tolerate laparotomy for ablation therapy.

Objective:To explorethe the clinical manifestations, treatment and prognosis of anastomotic pseudoaneurysm after renal transplantation caused by infection.Methods:Clinical data of 1 recipient with pseudoaneurysm after renal transplantation due to Pseudomonas aeruginosa infection were retrospectively analysed and combined with a literature review. Results:At Month 2 post-transplantation, the recipient developed right lower abdominal pain, and contrast-enhanced ultrasound examination showed a pseudoaneurysm at the artery anastomosis. Anti-infection and anti-rejection therapy had no obvious effect, and therefore next surgical exploration was performed. A size4.0 cm×3.5cm pseudoaneurysm was found intraoperatively at the graft renal artery anastomosis.After graft was evaluated as having no preservation value, the transplanted kidney and pseudoaneurysm were resected. Bacterial culture indicated Pseudomonas aeruginosa infection.The recipient recovered well and waited for next transplantation. Conclusions:Pseudoaneurysm of transplanted kidney is a very rare complication after renal transplantation, and caused by infection of Pseudomonas aeruginosa is more rarer, It has not been reported in mainland China.This type of recipient has the characteristics of high graft inactivation rate and high mortality rate. Timely surgical resection can effectively prevent the deterioration of disease.

Objective:To study the complications of irreversible electroporation (nano-knife) ablation on locally advanced pancreatic cancer, and to analyse the causes of complications and related treatment.Methods:The clinical data of 36 patients with locally advanced pancreatic cancer treated with nano-knife ablation at the Fifth Affiliated Hospital of Zhengzhou University from January 2016 to March 2019 were studied retrospectively. The types and incidence of postoperative complications were analyzed. The complications were classified according to the Clavien-Dindo classification, and the severity of the complications was evaluated.Results:There were 15 patients (41.7%) who developed various degrees of complications, including splenic infarction, atrial fibrillation, portal vein thrombosis, pancreatic fistula, pseudoaneurysm, gastrointestinal bleeding, liver abscess and severe pancreatitis. Among them, 6 patients (16.7%) had grade III complication or above. Three (8.3%) patients with grade Ⅲ complications died of upper gastrointestinal bleeding 3 months after operation.Conclusions:Various complications might occur after nano-knife ablation, with postoperative gastrointestinal and abdominal bleeding being the main complications which resulted in death. Measures which can effectively reduce occurrence of complications need to be studied.

Objective: To detect pathogenic gene variants in two Chinese families with cone-rod dystrophy(CORD). Methods: After the informed consent and comprehensive ophthalmic examinations for the patients, 3 mL peripheral blood was taken from the patients’ blood vessel and DNA was extracted. The DNA was sequenced by whole-exome sequencing technology and variants were analyzed. Results: Two novel compound heterozygous AIPL1 variants were detected in two patients, which were c. 923T>C(p.L308P) and c. 421C>T(p.Q141X) variants in Family 1, c. 572T>C(p.L191P) and c. 421C>T(p.Q141X) in Family 2 . Conclusion The results supported that AIPL1 gene variants are the main cause of the two CORD families. Whole-exome sequencing technology is a useful tool in the clinical differentiated diagnosis and genetic counseling for CORD patients.

Objective To study the effect of cardiac contractility modulation (CCM) on TGFβ1/Smad/CTGF signaling pathway.Methods A rabbit heart failure (HF) model was established by ligating the ascending aortic root.Thirty rabbits were divided into sham operation group (n=10),HF group (n=10) and CCM group (n=10).Myocardial tissue collagen Ⅰ and collagen Ⅲ were analyzed with Sirius red staining,myocardial tissue hydroxyproline level was measured by chromometry,and expressions of TGFβ1,Smad3,Smad7,CTGF were detected by Western blot in 3 groups.Results Collagen Ⅰ,collagen Ⅲ and hydroxyproline content were highcr in HF group than in sham operation group,while collagen Ⅰ,collagen Ⅲ and hydroxyproline conten were lower in CCM group than in sham operation group (0.69±0.05 μg/mg vs 0.98±0.04 μg/mg,P＜0.05).The expression levels of TGFβ1,Smad3,CTGF were higher while those of Smad7 were lower in HF group than in sham operation group (P＜0.05).The expression levels of TGFβ1,Smad3,CTGF were lower while those of Smad7 were higher in CCM group than in HF group (0.49±0.03 vs 0.67±0.04,0.43±0.06 vs 0.59±0.06,0.45±0.08 vs 0.75±0.09,P＜0.05;0.43±0.08vs 0.26±0.04,P＜0.05).Conclusion CCM can improve the myocardial fibrosis in HF rabbits by downregulating the expression of TGFβ1,Smad3,CTGF and upregulating the expression of Smad7.

OBJECTIVE:To provide reference for promoting the development of related legislation work on ensuring pediatric drug use in China. METHODS:The legislation process of pediatric drug use in US,the effects of current Best Pharmaceuticals for Children Act and Pediatric Research Equity Act on pediatric drug use in US were intrduced and analyzed,suggestions on guarantee-ing the accessibility and safety on pediatric drug use in China were put forward. RESULTS & CONCLUSIONS:The policy6-month period of pediatric exclusive protectionin Best Pharmaceuticals for Children Act has motivated the enthusiasm of phar-maceutical companies developing pediatric studies,while it affects the marketing of generic drugs. Pediatric Research Equity Act has achieved remarkable effect in terms of ensuring the safety of pediatric drug use by forcing pharmaceutical companies to carry out pediatrics assessments,while there is no enough force for the marketed drugs that has not been widely used for children. En-couragement and enforcement are useful methods for promoting development of pediatric drug use. It is suggested to take measures like modifingone drug two formsin Prescription Management Regulations,accelerating approvals of related pediatric drugs on the premise that safety is guaranteed,implementing tax preference for related pharmaceutical companies that produced pediatric drugs,promoting the entry of drug reimbursement list and empowering CFDA to force pharmaceutical companies to implement pedi-atric studies to promote the accessibility and safety of pediatric drugs.