Kinase modulators approved by FDA in 2022 / 药学学报

The FDA approved a total of 37 new drugs in 2022, including 22 new molecular entities and 15 new biological products. This is the year with the lowest number of new drugs approved by the FDA since 2017. Among these approved drugs, 21 new drugs belong to the "first-in-class" category, accounting for 56% of the total approved drugs, which is the highest ratio in the past 10 years. Among the drugs approved in 2022, there are 5 small molecule kinase modulators, including the tyrosine kinase 2 (TYK2) allosteric inhibitor deucravacitinib, the first oral pyruvate kinase (PK) activator mitapivat, the Janus kinase 1 (JAK1) selective inhibitor abcrocitinib, the JAK2 selective inhibitor pacritinib and the broad-spectrum fibroblast growth factor receptor (FGFR) inhibitor futibatinib. This review briefly describes the discovery background, research and development process, synthesis routes and clinical efficacy and safety of small molecule kinase modulators approved by the FDA in 2022, hoping to provide ideas and methods for further research on kinase modulators.

Efficacy of Tiaogan Huaxian Pills in Prevention and Treatment of Hepatic Fibrosis in Hepatitis B and Its Effect on Diffusion-weighted Imaging / 中国实验方剂学杂志

ObjectiveTo investigate the preventive and therapeutic effects of Tiaogan Huaxian pills combined with entecavir on hepatic fibrosis in chronic hepatitis B with liver Qi stagnation， spleen deficiency， and blood stasis syndrome and its effect on diffusion-weighted imaging （DWI）. MethodClinical data of 117 patients with liver disease who visited the Department of Hepatology at the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2021 to April 2022 were retrospectively analyzed. According to different treatment plans， they were divided into a control group （59 cases） and a treatment group （58 cases）. Both groups of patients received entecavir-based etiology treatment， and the treatment group added Tiaogan Huaxian pills on the basis of basic treatment. Both groups were treated for 24 weeks. Before and after treatment， the two groups were compared in terms of alanine aminotransferase （ALT）， advanced surgical technologies （AST）， total bilirubin （TBil）， hepatitis B virus （HBV）-DNA conversion rate， liver stiffness measurement （LSM）， four items of liver fibrosis （hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， and laminin）， the fibrosis index based on four factors （FIB-4）， the aspartate aminotransferase to platelet ratio index （APRI）， the apparent diffusion coefficient （ADC） value in magnetic resonance imaging （MRI）， and traditional Chinese medicine symptom scores， so as to analyze the efficacy of the two groups. ResultBefore treatment， there was no significant difference in ALT， AST， TBil， LSM， four items of liver fibrosis， FIB-4， APRI， HBV-DNA conversion rate， ADC value， and traditional Chinese medicine symptom scores between the two groups. After treatment， both groups of patients showed significant reductions in ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， and APRI （P<0.05） and a significant increase in ADC value （P<0.05） and HBV-DNA conversion rate （P<0.01）. The traditional Chinese medicine symptom score of the treatment group decreased significantly （P<0.05）. Compared with the control group after treatment， the effective rate of clinical traditional Chinese medicine in the treatment group was 91.38% （53/58）， which was significantly higher than that of the control group （54.23%， 32/59） （Z=-4.325， P<0.01）. In the treatment group， ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， APRI， and traditional Chinese medicine symptom scores all decreased significantly （P<0.05）， and the increase in ADC values was more significant （P<0.05）， while the difference in HBV-DNA conversion rate was not statistically significant. There were no serious adverse reactions or events in either group. ConclusionTiaogan Huaxian pills combined with entecavir have significant clinical efficacy in the treatment of hepatic fibrosis in chronic hepatitis B， which can reduce liver inflammation activity， delay hepatic fibrosis progression， and reduce traditional Chinese medicine symptom scores. It is worthy of clinical promotion and application.

Clinical Effect of Runzaoling Combined with Iguratimod on Primary Sjögren's Syndrome / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy and safety of iguratimod combined with the Chinese medicine Runzaoling in the treatment of primary Sjögren's syndrome （pSS）. MethodSeventy-two patients treated in the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine（TCM） from January 2021 to June 2022 who met the Western medical diagnosis of pSS and had the TCM syndrome of Yin deficiency and heat toxin syndrome were randomly assigned into an observation group and a control group， with 36 patients in each group. The observation group was treated with iguratimod combined with Runzaoling， and the control group was treated with iguratimod. The treatment in both groups lasted for 12 weeks. The clinical symptoms， EULAR Sjogren's syndrome patient reported index （ESSPRI）， EULAR Sjögren's syndrome disease activity index （ESSDAI）， erythrocyte sedimentation Rate （ESR）， C-reactive protein （CRP）， immunoglobulin （IgG）， Schirmer score， and saliva flow of the two groups were determined before and after treatment. Furthermore， the incidence of adverse reactions was compared between the two groups. ResultThe total response rate in the observation group was 75.0% （27 patients with response and 9 patients with no response）， which was higher than that （61.11%， 22 patients with response and 14 patients without response） in the control group （P<0.05）. After treatment， the ESSPRI， ESSDAI， and TCM syndrome scores in both groups decreased and the decreases were more obvious in the observation group than in the control group （P<0.05）. The treatment in both groups recovered the ESR， CRP， IgG， Schirmer score， and saliva flow （P<0.05）. Moreover， the observation outperformed the control group in terms of the ESR， CRP， IgG， and saliva flow （P<0.05） and had no significant difference in the Schirmer score compared with the control group. During the treatment period， 2 patients in the observation group had nausea， and 1 patient had an abnormal liver function， which were relieved after symptomatic treatment and did not affect the treatment. In the control group， 1 patient withdrew from the study due to rashes and showed no special discomfort in the follow-up 4 weeks， and 1 patient had nausea， which was relieved after symptomatic treatment. ConclusionIguratimod combined with Runzaoling has good clinical efficacy and safety in the treatment of pSS.

Evaluation of liposomal amphotericin B for the treatment of fungal keratitis in a tertiary eye care hospital

Purpose: To evaluate the efficacy of liposomal amphotericin B (L?AMB) for the treatment of fungal keratitis. Methods: Patients with fungal keratitis confirmed by potassium hydroxide (KOH) smear and/ or confocal microscopy were administered topical L?AMB and randomized into three groups treated with three different formulations. The medication was administered two hourly till clinical improvement was achieved, followed by six hourly till complete resolution. The outcome measures were time to clinical improvement, resolution of epithelial defect, stromal infiltrate, hypopyon, extent and density of corneal opacity, neovascularization, and best corrected visual acuity (BCVA) at 3 months. Results: Mean age of the patients was 46.6 ± 14.8 years, and trauma with vegetative matter was the most common predisposing factor. Aspergillus flavus (36%) was the most common fungus cultured, followed by Fusarium (23%). Mean time to clinical improvement, time to resolution of epithelial defect, mean time to resolution of infiltrate, and time to resolution of hypopyon were 3.45 ± 1.38, 25.35 ± 8.46, 37.97 ± 9.94, and 13.33 ± 4.90 days, respectively, and they were comparable among the three groups. There was a significant difference between treatment failure and success cases in terms of days of presentation (P < 0.01), size of the epithelial defect (P?value 0.04), and infiltrate size at presentation (P?value 0.04). At 3 months follow?up, no statistically significant difference was noted in BCVA and mean scar size among groups. Conclusion: L?AMB in a gel form is an effective antifungal agent that promotes the healing of fungal ulcers with notably least vascularization and better tolerance.

Clinical study of modified photodynamic therapy combined with Taohong Siwu Decoction in treating hypertrophic scar after severe burn

Abstract Objective: The aim of this study was to study the curative effect and the relative mechanism of modified photodynamic therapy combined with Taohong Siwu Decoction in the treatment of hyperplastic scar after severe burn, in order to provide a stable, safe and satisfactory scheme for scar repair. Methods: Forty cases with hyperplastic scars after severe burns admitted to the plastic surgery department from May 2021 to May 2022 were divided into a control group and an observation group by means of the random number table method. The control group was treated with ordinary laser therapy combined with Taohong Siwu Decoction, while the observation group was treated with modified photodynamic therapy combined with Taohong Siwu Decoction. The Vancouver Scar Scale (VSS) was assessed in both groups, and the clinical effectiveness of both groups was compared. HE-staining was performed on the scar tissue of the same patient before and after treatment to observe the changes in the arrangement of fibroblasts. The Vascular Endothelial Growth Factor (VEGF), β-Transforming Growth Factor (TGF-β), and Platelet-Derived Growth Factor (PDGF) in the tissue samples of both groups were detected by quantitative real-time PCR. The patients were followed up for 6 months, and their satisfaction, side effects, and scar recurrence were observed. Results: Compared with the control group, the VSS score in the observation group was lower (p < 0.05). The therapeutic effect of the observation group was superior to the control group after 3 months (p < 0.05). After 3-months of therapy, the arrangement of fibroblasts in the scar became looser in two groups, and the observation group was more looser. The VEGF, TGF-β and PDGF levels in tissue samples of the observation group were lower than those in the control group after 3 months of treatment (p < 0.05). The satisfaction of the observation group was higher than that of the control group (p < 0.05). The adverse reactions between the two groups showed no difference (p > 0.05), while the recurrence rate was lower in the observation group (p < 0.05). Conclusion: Modified photodynamic therapy combined with Taohong Siwu Decoction shows remarkable efficacy in patients with hyperplastic scars after severe burns. It can improve the color, thickness, vascular distribution, and softness of the scar, and reduce the level of cytokines related to tissue repair. At the same time, it can improve patients' satisfaction with the aesthetic appearance and reduce the recurrence rate, providing a new comprehensive therapy that is safer and more effective, simple and quick, and easy to promote in the clinic.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

Guanxin Danshen Dripping Pills Improve Quality of Life and Cardiovascular Prognoses of CHD Patients after PCI with Anxiety or Depression (GLAD Study): A Randomized Double-Blind Placebo-Controlled Study / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).@*METHODS@#From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12.@*RESULTS@#In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred.@*CONCLUSIONS@#GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).

Clinical Effect of Feining Paidu Decoction on Refractory Mycoplasma Pneumoniae Pneumonia in Child Patients / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Feining Paidu decoction on refractory Mycoplasma pneumoniae pneumonia in child patients. MethodA randomized controlled trial （RCT） was conducted， with 96 child patients randomly divided into a control group and an observation group， each containing 48 cases. The control group received intravenous azithromycin （10 mg·kg-1·d-1） for 7 days， intravenous methylprednisolone （1 mg·kg-1·d-1） for 3 days， along with supportive treatments such as fluid infusion and antipyretics. The observation group received oral administration of Feining Paidu decoction once a day for 7 days. Changes in traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， serum soluble B7-H3 （sB7-H3）， serum inflammatory factors， coagulation function， and lung imaging ［computer tomography（CT）］ scores were observed in both groups. Adverse reaction events were also recorded. ResultThe total effective rate in the observation group was 95.74% （45/47）， significantly higher than 80.43% （37/46） in the control group （Z=-3.702， P<0.01）. Compared with the results before treatment， TCM syndrome scores， lung imaging scores， sB7-H3， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， D-dimer （D-D）， and fibrinogen （FIB） levels in both groups all significantly decreased after treatment （P<0.05， P<0.01）. After treatment， the observation group showed significantly better results in these indicators than the control group （P<0.05， P<0.01）. There was no statistically significant difference in thrombin time （TT） in the control group before and after treatment， while the observation group showed a significant prolongation after treatment （P<0.05）. There were no statistically significant differences in activated partial thromboplastin time （APTT） and prothrombin time （PT） between the two groups before treatment， and no serious adverse reactions occurred in either group. ConclusionFeining Paidu decoction combined with conventional treatment can alleviate inflammatory responses， improve hypercoagulable states， promote the absorption of pulmonary inflammation， and enhance the clinical efficacy of refractory Mycoplasma pneumoniae pneumonia in children.

Safety and efficacy analysis of hepatic artery infusion chemotherapy combined with immune targeted therapy for single CNLC Ⅰb hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To investigate the safety and efficacy of FOLFOX (5-fluorouracil + calcium folinate + oxaliplatin) hepatic arterial infusion chemotherapy (FOLFOX-HAIC) combined with immune and targeted therapy as triple combination therapy for patients with single China Liver Cancer Staging (CNLC) Ⅰb hepatocellular carcinoma.Methods:A total of 20 patients with single CNLC Ⅰb hepatocellular carcinoma who received FOLFOX-HAIC combined with immune and targeted therapy as triple combination therapy in the First Affiliated Hospital of Guangxi Medical University from October 2021 to August 2022 were included. The clinical data of all patients was retrospectively analyzed. There were 18 males and 2 females, with the age of (55.1±9.9) years. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were used to evaluate the efficacy of FOLFOX-HAIC combined with immune and targeted therapy, and the clinical safety of triple combination therapy was evaluated by common terminology criteria for adverse events 4.0.Results:According to RECIST 1.1, objective response rate of 20 patients was 70.0% (14/20) and disease control rate was 100.0% (20/20) after 2 cycles of treatment (one cycle of FOLFOX-HAIC plus programmed death-1 antibody). According to mRECIST, objective response rate was 90.0% (18/20) and the disease control rate was 100.0% (20/20) after 2 cycles of treatment. Following the treatment, 12 patients (60.0%) received liver tumor resection, and all of them achieved R 0 resection, 2 patients (10.0%) received radiotherapy, 3 patients (15.0%) stopped drug treatment for surgery, 2 patients (10.0%) refused surgery, and 1 patient (5.0%) died of multiple organ failure caused by immune hepatitis. According to pathological results, 3 patients (25.0%, 3/12) achieved pathological complete response, and 4 patients (33.3%, 4/12) achieved major pathological response. In the safety evaluation, the overall incidence of adverse events was 100.0% (20/20). Seven patients (35.0%) had grade 3 adverse events and 1 patient (5.0%) died of multiple organ failure due to immune hepatitis (grade 5). Grade 1-3 adverse events could be relieved after symptomatic treatment. Conclusion:The triple combination therapy of FOLFOX-HAIC combined with immune and targeted therapy is safe and has high objective response rate and disease control rate, which could be a new strategy for the neoadjuvant treatment of hepatocellular carcinoma.

Effect of continuous renal replacement therapy on plasma concentration, clinical efficacy and safety of colistin sulfate / 中华危重病急救医学

Objective:To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate.Methods:Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups.Results:A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. ① There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE Ⅱ: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [μmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. ② Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). ③ Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. ④ Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. Conclusions:CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

Meta-analysis of the clinical efficacy of compound α-ketoacid tablets combined with low-protein diet in diabetic kidney disease / 中华临床营养杂志

Objective:To systematically evaluate the clinical efficacy of compound α-ketoacid tablets in the treatment of diabetic kidney disease (DKD).Methods:CNKI, Wanfang database, EMBASE, PubMed and Cochrane Library database were searched for eligible records published from the establishment of individual database to November 13 th, 2022. The quality of the included studies were assessed, data were extracted, and meta-analysis was conducted using RevMan5.3. Results:A total of 26 randomized controlled trials were included, with a total of 2 790 DKD patients (1 465 in the experimental group and 1 325 in the control group). Multiple parameters were significantly improved in the experimental group compared with the control group, including 24-hour urinary protein, blood creatinine, urea nitrogen, nutritional index, oxidative stress level, fasting blood glucose, glycated hemoglobin, homocysteine, HGF, VEGF, TGF-β1, and systolic blood pressure.Conclusions:Limited low-quality evidence showed that compound α-ketoacid tablets combined with low-protein diet may be related to the improved 24-hour urinary protein, renal function, and glucose metabolism in patients with DKD. Due to the lack of randomized controlled trials designed for respective stages of DKD, the inclusion criteria of our study were relatively general, possibly leading to the lack of pertinence of the results. Some indicators showed apparent heterogeneity among different groups, and more high-quality multi-center studies with large sample sizes are still needed to verify our findings.

Clinical efficacy of early versus delayed open reduction and internal fixation in the treatment of tibial pilon fracture / 中国基层医药

Objective:To investigate the clinical efficacy of early versus delayed open reduction and internal fixation in the treatment of tibial pilon fracture. Methods:Sixty patients with tibial pilon fractures admitted to Zhejiang Veteran Hospital from May 2018 to May 2021 were included in this study. They were randomly divided into a control group and a study group ( n = 30/group) using the coin-tossing method. Patients in the control group underwent early reduction and internal fixation within 3 days after injury. Patients in the study group underwent delayed reduction and internal fixation during 7-14 days after injury. The time to bone fracture healing and the time to independent weight-bearing walking were recorded. At 3 and 6 months after surgery, the American Orthopedic Foot and Ankle Society score, Visual Analogue Scale score, clinical efficacy, and incidence of complications were compared between the two groups. Results:The time to bone fracture healing and the time to independent weight-bearing walking in the study group were (8.23 ± 0.63) weeks and (11.77 ± 0.82) weeks, respectively, which were significantly shorter than (9.57 ± 0.86) weeks and (13.40 ± 0.93) weeks in the control group ( t = 6.87, 7.21, both P < 0.001). At 3 months after surgery, American Orthopedic Foot and Ankle Society score in the study group was significantly higher than that in the control group, and the Visual Analogue Scale score in the study group was significantly lower than that in the control group ( t = 6.69, 5.16, both P < 0.001). Overall excellent and good rate of clinical efficacy in the study group was significantly higher than that in the control group (86.6% vs. 63.3%, χ2 = 4.35, P = 0.037). At 6 months after surgery, there were no significant differences in American Orthopedic Foot and Ankle Society score and Visual Analogue Scale score between the two groups ( t = 0.96, 1.12, P = 0.339, 0.267). At 6 months after surgery, there was no significant difference in the overall excellent and good rate of clinical efficacy between the study and control groups (96.6% vs. 90.0%, χ2 = 0.26, P = 0.605). The incidence of complications in the study group was significantly lower than that in the control group (3.3% vs. 26.6%, χ2 = 4.70, P = 0.030). Conclusion:Delayed open reduction and internal fixation after reducing injury to the soft tissue of the affected limbs can effectively shorten the rehabilitation cycle of tibial pilon fracture, increase short-term efficacy, and decrease the risk of postoperative complications.

Efficacy and safety of dapagliflozin combined with metformin in treatment of type 2 diabetes mellitus / 中国医师进修杂志

Objective:To analyze the efficacy and safety of dapagliflozin combined with metformin in the treatment of type 2 diabetes.Methods:A prospective research method was adopted. A total of 60 patients with type 2 diabetes who were treated in Huainan Chaoyang Hospital from January 2019 to December 2021 were collected as research objects, and the above patients were divided into the observation group (30 cases) and the control group (30 cases) according to the random number table method. After admission, they were treated with oral metformin sustained-release tablets combined with exercise and diet control. On this basis, the observation group was treated with dapagliflozin, while the control group was treated with glimepiride. The blood glucose-related indexes after 3 months of treatment, blood lipid indexes after 1 month of treatment, and adverse reactions were compared between the two groups of patients.Results:After 3 months of treatment, the fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PBG) and glycosylated hemoglobin (HbA 1c) of the two groups were significantly lower than those before treatment, observation group: (6.60 ± 1.01) mmol/L vs. (7.76 ± 1.82) mmol/L, (10.43 ± 2.74) mmol/L vs. (14.05 ± 3.84) mmol/L, (5.90 ± 1.56)% vs. (8.46 ± 2.07)%; control group: (6.77 ± 0.95) mmol/L vs. (7.82 ± 1.38) mmol/L, (10.17 ± 2.23) mmol/L vs. (14.01 ± 2.63) mmol/L, (6.14 ± 1.51)% vs. (8.73 ± 1.58)% ( P<0.05), but there was no difference in FBG, 2 h PBG and HbA 1c between the two groups ( P>0.05). The total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the observation group were significantly lower than those in the control group: (5.02 ± 0.98) mmol/L vs. (5.71 ± 0.77) mmol/L, (2.81 ± 0.69) mmol/L vs. (3.39 ± 0.87) mmol/L ( P<0.05). There was no difference in adverse reactions ( P>0.05). Conclusions:For patients with type 2 diabetes mellitus, on the basis of metformin sustained-release therapy, whether combined with dapagliflozin or glimepiride therapy has good hypoglycemic effect, but dapagliflozin has more advantages in improving blood lipids.

Research progress of percutaneous nephrolithotomy in ambulatory surgery mode / 现代泌尿外科杂志

Ambulatory percutaneous nephrolithotomy (APNL) is the mode of treatment in which patients are admitted to hospital for percutaneous nephrolithotomy (PNL) and discharged smoothly within 24 hours, and the total length of hospital stay in special cases is less than 48 hours. APNL can optimize the utilization of hospital beds and upgrade patients’ satisfaction. Miniaturized channel has been applied to the preliminary exploration of APNL. The mode is often operated with paravertebral block and partial or total tubeless after surgery, which can reduce postoperative pain and shorten hospital stay. Meanwhile, the stone-free rate and postoperative complication rate are not significantly different from those of PNL. The key of successful APNL depends on strict screening of cases, and careful formulating of clinical pathways and emergency plans to standardize medical practices and improve service efficiency. This article reviews the clinical safety and efficacy of APNL and summarizes the criteria for selecting cases suitable for this mode.

Evaluation of clinical efficacy and prognostic factors in multiple myeloma patients treated with auto-HSCT: A single-center real-world study / 西安交通大学学报(医学版)

【Objective】 To evaluate the clinical efficacy and prognostic factors in multiple myeloma (MM) patients treated with autologous hematopoietic stem cell transplantation (auto-HSCT). 【Methods】 The clinical data of 155 MM patients newly diagnosed and suitable for transplantation in our hospital from 2014 to 2021 were retrospectively analyzed. They were divided into auto-HSCT group and non-auto-HSCT group according to the treatment mode. The clinical efficacy, overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Furthermore, the prognostic factors of auto-HSCT group were analyzed. 【Results】 ① There were 51 patients in auto-HSCT group and 104 patients in non-auto-HSCT group. There was no statistical difference in baseline characteristics except age between the two groups. ② Hematopoietic reconstruction was achieved in all patients in auto-HSCT group, and no transplantation-related mortality was found. ③ The clinical efficacy of pre-and post-transplantation was compared in auto-HSCT group. sCR/CR rate was significantly increased after transplantation (P=0.041). The effective remission rate (≥VGPR) was also higher (P=0.05). As for the best efficacy, sCR/CR rate and effective remission rate were both significantly higher in auto-HSCT group than in non-auto-HSCT group (P=0.001). ④ In auto-HSCT group, by the end of follow-up, the median OS was not reached, the median PFS was 30.5 months, and 3-year OS and PFS was 87% and 40.3%, respectively. In non-auto-HSCT group, the median OS was 61 months, the median PFS was 21 months, and 3-year OS and PFS was 65.3% and 33.1%, respectively. It indicated that OS was significantly prolonged in auto-HSCT group (P=0.004). PFS was also prolonged but without significant difference (P=0.065). ⑤ Analysis of prognostic factors in auto-HSCT group showed that decreased PLT (P=0.038) and increased serum-adjusted calcium (P=0.017) were independent risk factors for OS, decreased PLT (P=0.005), female (P=0.018) and disease status of PR or worse before transplantation (P=0.012) were independent risk factors for PFS. 【Conclusion】 Auto-HSCT can improve the remission rate, prolong OS in MM patients, and possibly prolong PFS. Increased serum-corrected calcium and decreased PLT are independent prognostic factors for OS in patients treated with auto-HSCT. Decreased PLT, female, and disease status of PR or worse before transplantation are independent prognostic factors for PFS.

Clinical observation of herombopag combined with recombinant human thrombopoietin in the treatment of primary immune thrombocytopenia / 中国药房

OBJECTIVE To investigate the clinical efficacy and safety of herombopag combined with recombinant human thrombopoietin （rhTPO） in the treatment of primary immune thrombocytopenia （ITP） in the real world. METHODS A retrospective study was conducted on the patients diagnosed with ITP in the Second Affiliated Hospital of Bengbu Medical College from January 2021 to December 2022. Among them， 98 patients who were treated with a combination of herombopag and rhTPO were included in the observation group， and 157 patients who were treated with rhTPO alone were included in the control group. The changes in platelet count， clinical efficacy， bleeding， platelet transfusion rate and adverse drug reactions before and after treatment were observed and compared between the two groups. RESULTS Since the 8th day of treatment， there was a statistically significant difference in platelet count between the two groups （[ 61.04±13.46）×109 L－1 in observation group， （52.11±12.06）× 109 L－1 in control group] （P＜0.05）， and there also was a statistically significant difference in the peak and stable values of platelet count between the two groups （P＜0.05）. The total effective rates of the observation group and the control group were 79.59% and 66.88%， with cumulative response rates of 81.32% and 68.68%， and median response durations of 8 days and 10 days， respectively； these differences were statistically significant （P＜0.05）. During the treatment period， the bleeding rates of the observation group and control group were 3.06% and 8.28% （P＜0.05）， bleeding events were categorized as grade 1 or 2， and platelet transfusion rates were 31.63% and 40.76%； the differences in bleeding rates and platelet transfusion rates between the two groups was statistically significant （P＜0.05）. The incidences of adverse drug reactions in the two groups were 11.22% and 9.55%， respectively， with no statistically significant difference （P＞0.05）， and no moderate to severe adverse drug reaction was found. CONCLUSIONS The combination of herombopag and rhTPO can significantly increase platelet levels and response rate， and reduce bleeding rate and platelet transfusion rate in ITP patients， with good safety.

Advances in clinical and safety studies of phosphodiesterase 4 inhibitors / 药学学报

Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.

Clinical Efficacy and Mechanism of Osteoking in Treatment of Knee Osteoarthritis Based on Real-world Data / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy and mechanisms of Osteoking in the treatment of knee osteoarthritis （KOA） in real-world practice， so as to provide a basis for the rational clinical use of Osteoking. MethodFrom the Osteoking for knee osteoarthritis case registration system， 638 KOA cases treated with Osteoking were selected and analyzed in SPSS 26.0. The clinical data were collected from 20 hospitals in China from May 2020 to December 2021. Descriptive analyses of patient age， gender， body mass index， course of treatment and other parameters were performed. The Mann-Whitney U test was performed to compare the visual analogue scale （VAS） and Western Ontario and McMaster universities arthritis index （WOMAC） scores before and after treatment. The integrative pharmacology-based research platform of traditional Chinese medicine （TCMIP） v2.0 was used for network analysis of the core targets of Osteoking in treating knee osteoarthritis. Furthermore， 20 KOA patients treated with Osteoking in the Third Affiliated Hospital of Beijing University of Chinese Medicine from October to December in 2022 were enrolled in the treatment group， and 20 healthy volunteers in the control group. The enzyme-linked immunosorbent assay was employed to measure the serum levels of related indicators to verify the prediction results. ResultA total of 638 KOA patients were treated with Osteoking， including 429 （67.24%） receiving Osteoking alone and 209 （32.76%） receiving Osteoking combined with other therapies. The female patients （415， 65.05%） were more than the male patients （223， 34.95%）. The patients showed the mean age of （63.48±13.51） years， mean body mass index of （24.09±2.98） kg·m-2， and mean course of treatment of （15.78±9.66） days. Most of the patients were rated as grades Ⅱ （46.24%） and Ⅲ （34.64%） in Kellgren-Lawrence （K-L） grading and in the relief stage （82.45%） in clinical staging. There was no significant correlation between clinical staging and K-L grading results. The cluster analysis identified three TCM syndromes： Qi stagnation and blood stasis， cold-dampness obstruction， and liver-kidney deficiency. The overall clinical efficacy evaluation showed that VAS score decreased from （6.01±0.85） scores before treatment to （2.54±1.73） scores after treatment （P<0.05）， and the WOMAC score decreased from （93.25±25.91） scores before treatment to （50.73±25.14） scores after treatment （P<0.05）. The network analysis predicted that Osteoking might regulate the transforming growth factor-beta （TGF-β）， tumor necrosis factor-alpha （TNF-α）， and nuclear factor-kappa B （NF-κB） signaling pathways to exert the therapeutic effect. The clinical trial showed elevated TGF-β1 level （P<0.01） and lowered NF-κB subunit RELA and tumor necrosis factor receptor superfamily， member 1A （TNFRSF1A） levels （P<0.05） after treatment. The synergistic effects of these changes provide a multidimensional and comprehensive therapeutic efficacy for KOA， alleviating the joint pain and limited mobility in patients. ConclusionOsteoking showed significant therapeutic efficacy in treating KOA. Osteoking may act on multiple pathways involved in cartilage metabolism and inflammation. The findings provide experimental evidence and theoretical support for elucidating the multi-target mechanism of Osteoking in treating KOA.

Effect of fluoxetine combined with Shugan Jieyu capsule in the treatment of patients with depression and its impact on heart rate variability / 四川精神卫生

BackgroundDepression is a kind of disease with relatively high suicide risk， which seriously affects the quality of life of patients and their families， and brings a great burden to society. Antidepressants in western medicine are effective， but the improvement of depressive symptoms is relatively limited by single use， and the combination of two antidepressants may increase the risk of adverse reactions in patients. The rational use of Chinese patent medicine and western medicine may play a complementary role， and the safety of Chinese patent medicine is high. ObjectiveTo explore the early clinical efficacy of fluoxetine combined with Shugan Jieyu capsule in the treatment of depression， and to compare the differences in efficacy， safety and influence on heart rate variability between fluoxetine combined with Shugan Jieyu capsule and fluoxetine alone， so as to provide references for clinical medication of depression patients. MethodsFrom December 2015 to June 2016， 64 patients who met the diagnostic criteria of depression in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） who were hospitalized in the Second Affiliated Hospital of Xinxiang Medical University were selected as the research objects， and were randomly divided into the combined medication group and the fluoxetine group with 32 patients in each group. Patients in both groups were treated with fluoxetine， while patients in the combined medication group were treated with Shugan Jieyu capsule on this basis. Patients in both groups were assessed with Hamilton Depression Scale-24 item （HAMD-24）， Hamilton Anxiety Scale （HAMA） and Heart Rate Variability （HRV） before treatment， and were assessed with HAMD-24 and Treatment Emergent Symptom Scale （TESS） at the end of the 2nd， 4th and 6th week of treatment， and HRV was analyzed again at the end of the 6th week of treatment. ResultsThe study ultimately included 60 patients with depression， with 30 cases in the combination therapy group and 30 cases in the fluoxetine group. At the end of the 2nd， 4th and 6th week of treatment， the HAMD-24 score of the combined drug group was lower than that of the fluoxetine group （t=-2.677， -3.960， -4.432， P<0.05 or 0.01）. Compared with before treatment， the 24-hour mean standard deviation of normal RR intervals （SDNN）， normal low frequency （nLF） and normal high frequency （nHF） in the combined treatment group were higher at the end of the 6th week （t=-73.970， -31.878， -38.721， P<0.01）， but significant lower in LF/HF （t=3.525， P<0.01）. At the end of the 6th week of treatment， the total effective rate of the combined treatment group was higher than that of fluoxetine group， and the difference was statistically significant （86.67% vs. 70.00%， χ2=18.764， P<0.01）. At the 2nd， 4th and 6th week of treatment， there was no significant difference in the number of adverse reactions between the two groups （P>0.05）. ConclusionCompared with fluoxetine alone， Shugan Jieyu capsule combined with fluoxetine may be better in clinical efficacy and improvement of heart rate variability in patients with depression， without increasing adverse reactions.

Efficacy comparison of intravitreal injection of Conbercept versus Aflibercept in the treatment of pachychoroid neovasculopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe and compare the clinical efficacy and safety of intravitreal injection of conbercept or aflibercept in the treatment of pachychoroid neovasculopathy(PNV).METHODS:Retrospective case-control study. A total of 33 patients(35 eyes)diagnosed as PNV in our hospital from February 2018 to October 2022 were divided into 14 cases(14 eyes)in conbercept group and 19 cases(21 eyes)in aflibercept group according to the treatment methods. The best corrected visual acuity(BCVA), subfoveal choroidal thickness(SFCT)and central macular thickness(CMT), injection times and clinical complications of the two groups were compared before and 1, 3 and 6mo after treatment.RESULTS:BCVA, CMT and SFCT in both groups were significantly improved after 1, 3 and 6mo of treatment(all P&#x0026;#x003C;0.05). During the whole follow-up period, the number of intravitreal injections in the two groups were 2(2, 3)and 2(1.5, 2)respectively, and there was no significant difference(P=0.423). No serious complications occurred during the treatment of the two groups.CONCLUSION:Both intravitreal injections of conbercept and aflibercept can treat PNV with similar therapeutic effects. The desired clinical outcome is achieved by improving the anatomy while improving visual acuity.