First-in-class small molecule drugs in 2023 / 药学学报

In 2023, drug discovery develops steadily, with improvement of small molecule drugs discovery keeps pace with biological drugs in this year. The Center for Drug Evaluation and Research of U.S. Food and Drug Administration has totally approved 55 kinds of new drugs which have significantly promotion compared to 37 new drugs approval in 2022, including 38 kinds of new molecular entities, 17 kinds of biological drugs, 5 kinds of gene therapeutics and 2 cell therapeutics. The proportion of first-in-class drugs increased steadily, with 13 small molecule first-in-class drugs and 7 biological first-in-class drugs approved this year, mostly in the fields of cancer and rare diseases. Among them, a plurality of first-initiated small molecule drugs exhibits breakthrough significance, such as the first neurokinin 3 (NK3) receptor antagonist fezolinetant, the first retinoic acid receptor (RIG-I) agonist palovarotene, the first protein kinase B (AKT) inhibitor capivasertib, the first complement factor B inhibitor iptacopan, etc. The pioneering drug has huge academic and commercial value, and has become the target of the academic and industrial circles. However, first-in-class drugs not only need new targets, new mechanisms and new molecules, but also need to comprehensively verify the causality between new targets and diseases, study the correlation between new mechanisms and drug efficacy, and explore the balance between new molecules and drug-manufacturing properties. This article analyzed the research background, development process and therapeutic application of three first-initiated small molecule drugs in this year, expecting to provide more research ideas and methods for more first-in-class drugs.

Synthesis of cello-oligosaccharides which promotes the growth of intestinal probiotics by multi-enzyme cascade reaction / 生物工程学报

Soluble cello-oligosaccharide with 2-6 oligosaccharide units is a kind of oligosaccharide with various biological functions, which can promote the proliferation of intestinal probiotics such as Bifidobacteria and Lactobacillus paracei. Therefore, it has a regulatory effect on human intestinal microbiota. In this study, a Cc 01 strain was constructed by expressing cellodextrin phosphorylase (CDP) in Escherichia coli. By combining with a previously constructed COS 01 strain, a three-enzyme cascade reaction system based on strains COS 01 and Cc 01 was developed, which can convert glucose and sucrose into cello-oligosaccharide. After optimization, the final titer of soluble cello-oligosaccharides with 2-6 oligosaccharide units reached 97 g/L, with a purity of about 97%. It contained cellobiose (16.8 wt%), cellotriose (49.8 wt%), cellotetrose (16.4 wt%), cellopentaose (11.5 wt%) and cellohexose (5.5 wt%). When using inulin, xylo-oligosaccharide and fructooligosaccharide as the control substrate, the biomass (OD600) of Lactobacillus casei (WSH 004), Lactobacillus paracei (WSH 005) and Lactobacillus acidophilus (WSH 006) on cello-oligosaccharides was about 2 folds higher than that of the control. This study demonstrated the efficient synthesis of cello-oligosaccharides by a three-enzyme cascade reaction and demonstrated that the synthesized cello-oligosaccharides was capable of promoting intestinal microbial proliferation.

Expression, thermal stability modification and application in PHB degradation of polyhydroxyalkanoate depolymerase from Thermomonospora umbrina / 生物工程学报

Polyhydroxyalkanoate depolymerase (PHAD) can be used for the degradation and recovery of polyhydroxyalkanoate (PHA). In order to develop a PHAD with good stability under high temperature, PHAD from Thermomonospora umbrina (TumPHAD) was heterelogously expressed in Escherichia coli BL21(DE3). At the same time, a mutant A190C/V240C with enhanced stability was obtained via rational design of disulfide bonds. Characterization of enzymatic properties showed that the mutant A190C/V240C had an optimum temperature of 60 ℃, which was 20 ℃ higher than that of the wild type. The half-life at 50 ℃ was 7 hours, at 50 ℃ which was 21 times longer than that of the wild type. The mutant A190C/V240C was used for the degradation of polyhydroxybutyrate (PHB), one of the typical PHA. At 50 ℃, the degradation rate of PHB being treated for 2 hours and 12 hours was 2.1 times and 3.8 times higher than that of the wild type, respectively. The TumPHAD mutant A190C/V240C obtained in this study shows tolerance to high temperature resistance, good thermal stability and strong PHB degradation ability, which may facilitate the degradation and recovery of PHB.

Research progress of the regulation of orphan nuclear receptors on chronic liver diseases / 生理学报

The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.

Effect of the area under the curve of carboplatin dosage on therapeutic efficacy and safety in Chinese patients with epithelial ovarian cancer / 西安交通大学学报(医学版)

【Objective】 To retrospectively analyze the average carboplatin dosage and calculate the area under the curve (AUC) using the Calvert formula in first-line chemotherapy in patients with epithelial ovarian cancer in The First Affiliated Hospital of Xi’an Jiaotong University so as to evaluate the effect of the AUC difference in the Chinese population on therapeutic efficacy and safety. 【Methods】 We enrolled patients who underwent first-line chemotherapy with paclitaxel and carboplatin 3-week regimen in our hospital from January 1, 2012 to January 1, 2022. According to the median of AUC, the patients were divided into high-dose group and low-dose group. The overall response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs) were compared. 【Results】 A total of 153 patients were enrolled in this study and the median AUC of carboplatin was 3.981 (range 2.314-5.446). Only 10.46% patients (16/153) had an AUC above 5. There were 77 patients with the AUC0.05). The ORR in the low-dose group and the high-dose group was 59.74% and 57.89%, respectively, and the DCR was 87.01% and 85.53%, respectively. The median PFS of the two groups was 14 and 15.5 months, respectively, and the median OS was 50 and 55 months, respectively. None of the above outcomes were statistically different between the two groups (P>0.05). The two groups showed significant differences in the incidence of anemia, neutropenia, and thrombocytopenia (P<0.05). The incidence of nausea and vomiting, grade 1-2 diarrhea or constipation, and grade 1-2 fever showed significant differences (P<0.05). In addition, the incidence of dose limiting toxicity (DLT), including grade 4 thrombocytopenia and febrile neutropenia (FN), was significantly increased in the high-dose group (P<0.05). 【Conclusion】 Compared with the recommended AUC 5-6 of carboplatin abroad, the actual carboplatin dosage in the first-line chemotherapy for patients with epithelial ovarian cancer was generally insufficient in our hospital. There was no difference in therapeutic efficacy between the patients with AUC<4 and AUC≥4. However, considering the increased risk of some AEs and DLT in the high-dose group, it is not recommended to increase the carboplatin AUC blindly.

A Case Report of Nevus Trichilemmocysticus / 罕见病研究

This article reports a case of nevus trichilemmocysticus. The patient, a 48-year-old man, presented with multiple filiform keratoses and nodules. Physical examination identified multiple subcutaneous papules and nodules on the scalp, filiform keratoses on the face and bilateral ears, in addition to linear blackheads on trunk and limbs. The patient also exhibited hair loss and hypoplastic tooth. Histopathology revealed trichilemmal cyst. Nevus trichilemmocysticus is a rare organoid nevus. We reviewed literature in order to raise the awareness of the syndrome.

Predictive value of preoperative liver function for perioperative massive blood transfusion in patients undergoing ascending aorta surgery / 中国输血杂志

【Objective】 To explore the predictive value of preoperative liver function for massive blood transfusion (MBT) in patients undergoing ascending aorta surgery. 【Methods】 Data from 238 patients undergoing ascending aorta surgery in the Department of Cardiovascular Surgery at The Affiliated Lihuili Hospital of Ningbo University were collected. Preoperative liver function tests were performed for all patients. Based on the perioperative transfusion volumes of red blood cell suspension, patients were divided into the MBT group, non-MBT group, and no blood transfusion (NBT) group. Clinical data during the perioperative period were compared among different groups. Receiver operating characteristic curve (ROC curve) analysis was used to assess the predictive value of liver function indicators for MBT and determine cut-off values. 【Results】 Compared with the non-MBT group and NBT group, the MBT group showed statistically significant differences in preoperative levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct bilirubin (DBIL), and serum albumin (SA) (P28.50 U/L, ALT >40.00 U/L, SA ≤34.55 g/L, and DBIL >4.25 μmol/L, there was a significant increase in the transfusion volume of various blood components and the incidence of MBT. 【Conclusion】 Preoperative liver function indicators (AST, ALT, SA, DBIL) have a moderate predictive value for MBT in patients undergoing ascending aorta surgery.

Role and research progress of circular RNA in Alzheimer’s disease / 解剖学报

[Abstract] The circular RNA (circRNA) is a class of endogenous expressed non-coding RNA that are formed by covalently closed cyclization through reverse splicing. In recent years, a variety of highly conserved and cell-type specific circRNA have been identified in eukaryotes. Alzheimer’ s disease (AD) is a common neurodegenerative disease and the most common cause of dementia in the elderly. Recent studies had shown that circRNA was involved in the pathogenesis and development of AD, such as amyloid β-protein (Aβ) metabolic, neuroinflammation, oxidative stress, autophagy and synaptic plasticity. The role and application value of circRNA in AD pathology are reviewed to provide a theoretical basis for the application of circRNA in the treatment and diagnosis of AD.

Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study / 中国药理学通报

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.

Mechanism of cucurbitacin B suppresses proliferation of hepatocellular carcinoma Huh-7 cells via inducing ferroptosis / 中国药理学通报

Aim To study the effects of cucurbitacin B (Cu B) on proliferation of hepatocellular carcinoma Huh-7 cells and its mechanism. Methods CCK-8 was used to detect the survival rate of Huh-7 cells with different concentrations of Cu B. Huh-7 cells were treated with Cu B (0. 5, 1, 2 njnol; L

Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector (VSVMT) in golden syrian hamster

COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.

Orchestrating antigen delivery and presentation efficiency in lymph node by nanoparticle shape for immune response

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4+ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8+ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Six new coumarins from the roots of Toddalia asiatica and their anti-inflammatory activities / 中国天然药物

We reported the discovery of six novel coumarins, toddasirins A-F (1-6), each endowed with modified isoprenyl or geranyl side chains, derived from the roots of Toddalia asiatica. Comprehensive structural elucidation was achieved through multispectroscopic analyses, single-crystal X-ray diffraction experiments, and advanced quantum mechanical electronic circular dichroism (ECD) calculations. Furthermore, the anti-inflammatory activity of these compounds was assessed. Notably, compounds 1-3 and 6 demonstrated notable inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells, with 50% inhibitory concentration (IC50) values of 3.22, 4.78, 8.90, and 4.31 μmol·L-1, respectively.

Establishment of a reporter system for estimating activation of human hepatic stellate cells based on COL1A1 promoter and enhanced green fluorescent protein / 北京大学学报(医学版)

OBJECTIVE@#To establish a visual reporting system for evaluating the activity of collagen Ⅰ α 1 chain (COL1A1) gene promoter in immortalized human hepatic stellate cells, so as to estimate the activation status of the cells and provide a new cell model for the screening and study of anti-hepatic fibrosis drugs.@*METHODS@#The promoter sequence of human COL1A1 was amplified from the genomic DNA of human hepatocarcinoma cell line HepG2. Based on the pLVX-AcGFP1-N1 plasmid, the recombinant plasmid pLVX-COL1A1-enhanced green fluorescent protein (EGFP) was constructed, in which the enhanced green fluorescent protein gene expression was regulated by the COL1A1 promoter. The monoclonal cell line was acquired by stably transfecting pLVX-COL1A1-EGFP into the immortalized human hepatic stellate cell line LX-2 by the lentivirus packaging system and screening. The cell line was treated with transforming growth factor-β1 (TGF-β1) or co-treated with TGF-β1 and drugs with potential anti-hepatic fibrosis effects. The EGFP fluorescence intensity in cells was analyzed by the fluorescence microscope and ImageJ 1.49 software using a semi-quantitative method. The COL1A1 and EGFP mRNA were detected by reverse transcription real-time quantitative PCR (RT-qPCR), and corresponding proteins were detected by Western blot.@*RESULTS@#The recombinant plasmid pLVX-COL1A1-EGFP with the expression of EGFP regulated by COL1A1 promoter was successfully constructed. Kozak sequence was added to enhance the expression of EGFP, which was identified by double digestion and sequencing. The LX-2 monoclonal cell line LX-2-CE stably transfected with pLVX-COL1A1-EGFP was obtained. After co-treatment with TGF-β1 and 5 μmol/L dihydrotanshinone Ⅰ with potential anti-hepatic fibrosis effect for 24 h, the total fluorescence intensity and the average fluorescence intensity of LX-2-CE were lower than those in TGF-β1 single treatment group (P < 0.05), the intracellular mRNA and protein levels of COL1A1 and EGFP were also lower than those in the TGF-β1 single treatment group (P < 0.05).@*CONCLUSION@#A reporter system for estimating activation of hepatic stellate cells based on COL1A1 promoter regulated EGFP expression is successfully constructed, which could visually report the changes in COL1A1 expression, one of the activation-related markers of hepatic stellate cells, in vitro. It provides a new cell model for the screening and study of anti-hepatic fibrosis drugs.

miRNA-128-3p inhibits malignant behavior of glioma cells by downregulating KLHDC8A expression / 南方医科大学学报

OBJECTIVE@#To determine whether miRNA-128-3p regulates malignant biological behavior of glioma cells by targeting KLHDC8A.@*METHODS@#Dual-luciferase reporter assays, qRT-PCR and Western blotting were used to verify the targeting of miRNA-128-3p to KLHDC8A. Edu assay, flow cytometry, Transwell assay and would healing assay were used to determine the effects of changes in miRNA-128-3p and KLHDC8A expression levels on malignant behavior of glioma cells. Rescue experiment was carried out to verify that miRNA-128-3p regulated glioma cell proliferation, apoptosis, invasion and migration by targeting KLHDC8A.@*RESULTS@#The expression level of KLHDC8A was significantly increased in high-grade glioma tissue and was closely related to a poor survival outcome of the patients. Overexpression of KLHDC8A promoted glioma cell proliferation, migration and invasion, and miRNA-128-3p overexpression inhibited proliferative and metastatic capacities of glioma cells. Mechanistically, KLHDC8A expression was directly modulated by miRNA-128-3p, which, by targeting KLHDC8A, inhibited malignant behavior of glioma cells.@*CONCLUSION@#Upregulation of miRNA-128-3p inhibits uncontrolled growth of glioma cells by negatively regulating KLHDC8A expression and its downstream effectors, suggesting that the miRNA-128-3p-KLHDC8A axis may serve as a potential prognostic indicator and a therapeutic target for developing new strategies for glioma treatment.

Hypercalcium crisis and postoperative hungry bone syndrome caused by primary hyperparathyroidism: a case report / 临床耳鼻咽喉头颈外科杂志

To review the diagnosis and treatment of a case of hypercalcium crisis caused by primary hyperparathyroidism（PHPT） and prophylactic treatment of hungry bone syndrome. In a 32-year-old male with hypercalcemia, the main manifestations were loss of appetite, nausea, polyuria, polydipsia, fatigue, lethargy, etc. parathyroid hormone, serum calcium increased, thyroid function was normal, thyroid color ultrasound and MRI showed space-occupying behind the right thyroid, radionuclide examination showed abnormal imaging agent concentration in the right parathyroid area, there was a history of pathological fracture. Clinically diagnosed as hypercalcemia crisis secondary to PHPT.

Comparison of Effects of Liuzijue Exercise and Conventional Respiratory Training on Patients after Cardiac Surgery: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the feasibility and safety of Liuzijue exercise (LE) for the clinical effect in patients after cardiac surgery.@*METHODS@#Totally 120 patients who underwent cardiac surgery and were admitted to the Cardiothoracic Intensive Care Unit of Nanjing Drum Tower Hospital between July and Oclober, 2022 were allocated to the LE group, the conventional respiratory training (CRT) group, and the control group by a random number table at a ratio of 1:1:1; 40 patients in each group. All patients received routine treatment and cardiac rehabilitation. LE group and CRT group respectively performed LE and CRT once a day for 30 min for 7 days. Control group did not receive specialized respiratory training. The forced vital capacity, forced expiratory volume in 1 s, peak inspiratory flow rate, peak expiratory flow rate, maximum inspiratory pressure, maximum expiratory pressure, modified Barthel index (MBI), and Hamilton Rating Scale for Anxiety (HAM-A) were evaluated before, after 3 and 7 days of intervention. In addition, the postoperative length of hospital stay (LOS) and the adverse events that occurred during the intervention period were compared.@*RESULTS@#A total of 107 patients completed the study, 120 patients were included in the analysis. After 3 days of intervention, the pulmonary function, respiratory muscle strength, MBI and HAM-A of all 3 groups improved compared with that before the intervention (P<0.05 or P<0.01). Compared with the control group, pulmonary function and respiratory muscle strength were significantly improved in the CRT and LE groups (P<0.05 or P<0.01). MBI and HAM-A were significantly improved in the LE group compared with the control and CRT groups (P<0.05 or P<0.01). On the 7th day after intervention, the difference was still statistically significant (P<0.01), and was significantly different from that on the 3rd day (P<0.05 or P<0.01). In addition, on the 7th day of intervention, the pulmonary function and respiratory muscle strength in the LE group were significantly improved compared with those in the CRT group (P<0.01). MBI and HAM-A were significantly improved in the CRT group compared with the control group (P<0.01). There were no significant differences in postoperative LOS among the 3 groups (P>0.05). No training-related adverse events occurred during the intervention period.@*CONCLUSIONS@#LE is safe and feasible for improving pulmonary function, respiratory muscle strength, the ability to complete activities of daily living and for relieving anxiety of patients after cardiac surgery (Registration No. ChiCTR2200062964).

Comparative study on the treatment of rhegmatogenous retinal detachment between foldable capsular body and scleral buckling / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the effectiveness and complications of treating rhegmatogenous retinal detachment(RRD)with foldable capsule body(FCB)and scleral buckling(SB).METHODS: The clinical data of 81 patients(82 eyes)with RRD who underwent surgery at our hospital from March 2019 to April 2022 were retrospectively analyzed. The differences in retinal reattachment rate, best-corrected visual acuity, the absorption of subretinal fluid, postoperative discomfort and incidence of complications between the two treatments were compared.RESULTS: The retinal reattachment rate was 96% in the FCB group and 92% in the SB group, with no significant difference between the two groups(P&#x003E;0.05). The best corrected visual acuity of the affected macular eyes was different in the both groups(P&#x003C;0.01). Both groups effectively promoted the absorption of subretinal fluid. The operation time of FCB group was 16.50(12.75, 25.00)min, while it was 38.00(36.25, 41.75)min in the SB group(P&#x003C;0.001). Patients in the FCB group also had significantly lower eyelid swelling and pain symptoms than those in the SB group(P&#x003C;0.001). The visual analogue scale(VAS)score at 1d after operation was 1.00(0.00, 2.00)in the FCB group and 3.00(2.00, 3.00)in the SB group(P&#x003C;0.001).CONCLUSION: FCB is a safe and effective surgical method to treat RRD that can alleviate patient's pain. Furthermore, FCB has a significantly shorter operation time and milder postoperative adverse reactions than SB.

Mechanism of Guishao Yunpi Decoction in Prevention and Treatment of Mammary Gland Hyperplasia Based on PTEN/PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveStudy on the mechanism of Guishao Yunpi decoction in preventing and treating breast hyperplasia based on phosphatase and tensin homolog （PTEN）/ phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodSeventy SPF-grade SD rats were randomly assigned into blank group （n=15） and modeling group （n=55）. The mammary gland hyperplasia model of liver stagnation and spleen deficiency was established by the comprehensive modeling method （hunger and satiety abnormality + tail stimulation + estradiol benzoate + progesterone）， and then 5 rats were randomly selected for model verification. The modeled rats were then randomly assigned into five groups： model group， positive control （4 mg·kg-1·d-1 tamoxifen） group， and high-， medium-， and low-dose （17.2， 8.6， 4.3 g·kg-1·d-1， respectively） Guishao Yunpi decoction groups， with 10 rats in each group. The rats in the blank group and model group were given 10 mL·kg-1·d-1 distilled water， and those in other groups were orally administrated with corresponding drugs. After 30 days of treatment， the general living conditions of rats were observed， and the thickness of breast tissue was measured by an ultrasonic diagnostic instrument. The open field test was carried out for behavioral evaluation. The levels of B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X （Bax） in the breast tissue were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein levels of PTEN， PI3K， and Akt in the breast tissue were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with those in the blank group， the rats in the model group were irritable， curled up in clusters， and showed positive behavior in the open field test. The modeling led to nipple swelling and increased the breast thickness （P<0.05）. Moreover， the modeling elevated the level of Bcl-2 and lowered that of Bax in the breast tissue （P<0.05）， down-regulated the mRNA and protein levels of PTEN， and up-regulated the mRNA and protein levels of PI3K and Akt （P<0.05）. Compared with the model group， drug administration relieved the general survival state， the degree of nipple swelling， and the positive behavior in the open field test and reduced the breast thickness （P<0.05）. In addition， drug administration reduced the level of Bcl-2 and increased that of Bax in the breast tissue （P<0.05）， up-regulated the mRNA and protein levels of PTEN， and down-regulated the mRNA and protein levels of PI3K and Akt （P<0.05）. ConclusionGuishao Yunpi decoction can improve the general living conditions and alleviate the mammary gland hyperplasia of rats with the syndrome of liver depression and spleen deficiency， which may be realized by the regulation of the PTEN/PI3K/Akt pathway.