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.

Xiangsha Liu Junzitang for Prevention and Treatment of Gastric Cancer： A Review / 中国实验方剂学杂志

Gastric cancer is one of the malignancies with high incidence in the world. Xiangsha Liu Junzitang，a common prescription for the prevention and treatment of gastric cancer，has the effects of moving Qi to relieve pain，drying dampness， and invigorating the spleen. It is especially indicated for gastric cancer of the spleen and stomach qi deficiency syndrome. Based on the databases such as CNKI，Wanfang Data，and PubMed，the clinical efficacy and experimental studies of Xiangsha Liu Junzitang for the prevention and treatment of gastric cancer were summarized and sorted out，and the mechanism of Xiangsha Liu Junzitang for the prevention and treatment of gastric cancer was elaborated in order to provide useful references for the clinical and basic research on Xiangsha Liu Junzitang in the field of gastric cancer in the future. In clinical practice，Xiangsha Liu Junzitang can treat gastric precancerous lesions，increase the body immunity of patients with gastric cancer，improve the symptoms of spleen and stomach weakness after gastric cancer surgery，and reduce the adverse reactions of the digestive tract after chemotherapy for gastric cancer. Its clinical efficacy is superior to that of western medicine alone whether it is combined with western medicine or used alone. In the experimental research，Xiangsha Liu Junzitang has the effects of regulating inflammatory factors，inhibiting the proliferation of gastric cancer cells，promoting the apoptosis of gastric cancer cells，and improving the activity of pepsin. Modern pharmacological research has shown that Xiangsha Liu Junzitang can conduct a comprehensive intervention with multiple components and multiple targets. The main components of a single drug contained include saponins，polysaccharides，lactones，volatile oils，organic acids，and others， with the effects of protecting gastric mucosa，regulating endocrine，and promoting apoptosis of epithelial cells in gastric mucosal dysplasia，reflecting the advantages and values of traditional Chinese medicine in the prevention and treatment of gastric cancer.

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.

Meta-analysis on Xixian Tongshuan Capsules/Pills combined with western medicine in treating cerebral infarction / 国际中医中药杂志

Objective:To systematically evaluate the clinical efficacy and safety of Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction.Methods:All RCTs about Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction were retrieved from CNKI, Wanfang Database, VIP database, PubMed and CBM. The search period was from the database establishment to December 31, 2021. Two researchers independently extracted the basic literature data and evaluated the methodological quality, then used RevMan5.4 software for meta-analysis.Results:Totally 9 articles were included, involving a total of 988 patients, including 505 cases in the observation group and 483 cases in the control group. Meta-analysis showed that the total effective rate of Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction was higher than that of conventional Western medicine [ RR=1.20, 95% CI (1.13, 1.27), P<0.05]. At the same time, the effect of NIHSS score, Barthel score and FIB were better than those of conventional Western medicine [respectively: MD=-3.21, 95% CI (-4.45, -1.97), P<0.05; MD=11.83, 95% CI (10.66, 13.00), P<0.05; MD=-0.95, 95% CI (-1.36, -0.54), P<0.05]. After treatment with Xixian Tongshuan Capsules/Pills combined with Western medicine, the adverse reactions mainly included dizziness, nausea, indigestion, rash, facial blushing, etc. There was no statistically significant difference in safety between the two groups [ RR=1.50, 95% CI (0.75, 3.01), P>0.05]. Conclusions:Under the treatment of conventional Western medicine, the addition of Xixian Tongshuan Capsules/Pills can improve the clinical efficacy of cerebral infarction treatment, effectively improve the symptoms of neurological impairment, improve the ability of daily life, and promote the prognosis and recovery, and without increasing the incidence of adverse reactions. However, large sample and high quality studies are still needed to support the conclusion.

Effect of self-made Bushen Jiangu Decoction combined with conventional western medicine therapy on the postoperative efficacy and bone transformation markers of osteoporotic vertebral compression fracture in the elderly / 国际中医中药杂志

Objective:To investigate the effect of self-made Bushen Jiangu Decoction on bone transformation markers in elderly patients with osteoporotic vertebral compression fracture after operation, and to evaluate the clinical efficacy.Methods:Prospective cohort study. A total of 92 patients with osteoporotic vertebral compression fracture after operation in Fangshan Hospital of Beijing University of Chinese Medicine from April 2020 to December 2021 who met the inclusion criteria were divided into 2 groups by random drawing method, with 46 in each group. The control group was treated with routine western medicine after operation, and the observation group was treated with self-made Bushen Jiangu Decoction on the basis of the control group. Both groups were treated for 3 months. TCM symptom scores were performed before and after treatment, and the prognosis of the patients was evaluated with the Chinese Osteoporosis Quality of Life (COQOL), VAS scale, and the Oswestry Dysfunction Index (ODI). The levels of amino terminal propeptide (PINP), cross-linked terminal peptide β special sequence (β-CTX) and bone morphogenetic protein 6 (BMP6) of type Ⅰ procollagen were determined by contrast chromogenic method with o-benzaldehyde. The adverse reactions during treatment were recorded and the clinical efficacy was evaluated.Results:The total effective rate was 95.7% (44/46) in the observation group and 82.6% (38/46) in the control group, and there was a significant difference between the two groups ( χ 2=4.04 , P=0.044). After treatment, the scores of fracture nonunion, pain in back and loin, chilliness and lassitude, and pallor in the observation group were significantly lower than those in the control group ( t values were 4.84, 4.09, 4.87, 4.14, respectively, P<0.01). The scores of COQOL, VAS and ODI in the observation group were significantly lower than those in the control group ( t values were 6.26, 10.57 and 6.15, respectively, P<0.01). The levels of PINP [(44.93±5.86)μg/L vs. (49.76±6.02)μg/L, t=3.90] and β-CTX [(0.49±0.17) μg/L vs. (0.68±0.20) μg/L, t=4.91] in observation group were significantly lower than those in the control group after treatment ( P<0.05). The level of BMP6 [(81.23±9.14) μg/L vs. (75.14±8.25) μg/L, t=3.36] in observation group was significantly higher than that of the control group ( P<0.05). During the treatment,the incidence of adverse reactions in the observation group was 13.0% (6/46), while that in the control group was 8.7% (4/46), and there was no significant difference between the two groups ( χ 2=0.45, P=0.503). Conclusion:The self-made Bushen Jiangu Decoction combined with conventional western medicine therapy can adjust the level of bone transformation markers in elderly patients with osteoporotic vertebral compression fractures, improve the lumbar function and quality of life, and improve the clinical efficacy.

Clinical study on modified Guipi Decoction combined with omeprazole in the treatment of acute non-variceal upper gastrointestinal bleeding with failure of the spleen to control blood vessels syndrome / 国际中医中药杂志

Objective:To investigate the clinical efficacy of modified Guipi Decoction combined with omeprazole in the treatment of acute non-variceal upper gastrointestinal bleeding (ANVUGIB) with failure of the spleen to control blood vessels syndrome.Methods:Prospective cohort study. A total of 120 patients from January 2018 to December 2021 Taihe County Hospital of Traditional Chinese Medicine with ANVUGIB of failure of the spleen to control blood vessels syndrome were selected, and the patients were divided into observation group and control group according to the random number table method, with 60 cases in each group. The control group was treated with a large dosage of proton pump inhibitor (omeprazole injection was injected intravenously first, and then omeprazole enteric coated tablets were taken); the observation group took Guipi Decoction on the basis of the control group, and both groups were treated for 7 days. TCM syndrome score, Hemoglobin (Hb) and hematocrit (HCT) levels were measured by colorimetry before and after the treatment. BUN was detected by urease glutamate dehydrogenase method. Prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) levels were detected by immunoturbidimetry. The adverse reactions during treatment were recorded and the clinical efficacy was evaluated.Results:Two patients in the observation group and two patients in the control group dropped out of the study. After treatment, the scores of main symptoms, secondary symptoms and total scores in the observation group were lower than those in the control group ( t values were respectively 10.73, 4.45, 7.98, P<0.05). After treatment, the levels of HCT [(41.25 ± 5.03)% vs. (38.19 ± 5.26)%, t=2.95], Hb [(81.09 ± 5.23) g/L vs. (78.39 ± 5.37) g/L, t=2.74] in the observation group were higher than those in the control group ( P<0.01), and BUN [(4.38±0.96) mmol/L vs. (5.39 ± 1.13) mmol/L, t=5.19] was lower than that in the control group ( P<0.01); PT [(12.48 ± 0.67) s vs. (13.22 ± 0.73) s, t=5.69], APTT [(24.66 ± 2.29) s vs. (27.78 ± 2.04) s, t=7.75] were lower than those in the control group ( P<0.01), and FIB [(3.68 ± 0.62) g/L vs. (3.41 ± 0.74) g/L, t=2.13] level was higher than that in the control group ( P<0.05). The total effective rate of the observation group was 93.1% (54/58), and that of the control group was 79.3% (46/58), with statistical significance ( χ2=4.64, P=0.031). During the treatment, the incidence of adverse reactions in the control group was 3.4% (2/58), while that in the observation group was 1.7% (1/58), without statistical significance ( χ2=0.34, P=0.559). Conclusion:High-dosage omeprazole treatment with the addition of internal administration of Guipi Decoction can significantly improve coagulation function, correct the signs and symptoms associated with insufficient blood volume in the body circulation, improve hemostatic efficiency, and reduce the risk of bleeding in patients with ANVUGIB, without increasing the risk of patient safety with the drug.

Clinical analysis of P2Y2 receptor agonist in the treatment of diabetic dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical efficacy of P2Y2 agonist diquafosol sodium(DQS)eye drops in the treatment of diabetic dry eye.METHODS: A total of 80 patients(160 eyes)with diabetic dry eye who admitted to our hospital from January 2022 to March 2022 were selected. They were randomly divided into study group and control group. A total of 40 patients(80 eyes)in the study group were treated with 3% DQS eye drops and 40 patients(80 eyes)in the control group were treated with 0.3% sodium hyaluronate eye drops. The ocular surface disease index(OSDI)score, non-invasive tear meniscus height(NITMH), first non-invasive tear film break-up time(NIBUTf), average non-invasive tear film break-up time(NIBUTav), tarsal gland loss score, lipid layer thickness grade and bulbar redness analysis(including conjunctival grade and ciliary grade), were examined before treatment and at 1wk, 1 and 3mo after treatment, respectively. Furthermore, corneal fluorescence staining and conjunctival lissamine green staining were analyzed based on the ocular surface staining score(OSS), and the conjunctival impression cytology and confocal microscopy were evaluated before and 3mo after treatment, respectively.RESULTS: There were no differences in OSDI score, tarsal gland loss score, conjunctival grade score and ciliary grade score between the two groups before and after treatment(P&#x0026;#x003E;0.05). OSS scores in the study group were lower than those in the control group, while NITMH, NIBUTf and NIBUTav were higher than those in the control group at 1 and 3mo after treatment(P&#x0026;#x003C;0.05). After 3mo of treatment, the density of conjunctival goblet cells increased and corneal dendritic cells decreased in the study group compared with the baseline(all P&#x0026;#x003C;0.05), while there were no significant changes in the control group compared with the baseline(all P&#x0026;#x003E;0.05).CONCLUSION: 3% DQS eye drops were effective in treating diabetic dry eye without serious complications.

Efficacy and safety of 4 kinds of hemocoagulases combined with proton pump inhibitor for nonvariceal upper gastrointestinal bleeding：a network meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the difference of efficacy and safety of four kinds of commonly used haemocoagulases combined with proton pump inhibitor （PPI） for nonvariceal upper gastrointestinal bleeding （NVUGIB）， and to provide evidence-based basis for clinical decision-making. METHODS Retrieved from PubMed， Web of Science， Wanfang data， VIP and CNKI databases， randomized controlled trials （RCTs） or cohort studies about Hemocoagulase agkistrodon blomhoffii， Haemocoagulase agkistrodon， hemocoagulase and Hemocoagulase bothrops atrox combined with PPI were collected during the inception to Dec. 2021. Two researchers independently screened the literature， extracted data and evaluated the quality of included studies. ADDIS 1.16.8 software was used to conduct a Bayesian network meta-analysis. RESULTS A total of 33 studies were included， involving 3 602 patients. Results of network meta-analysis showed that： in terms of hemostatic efficacy， compared with PPI monotherapy， four kinds of haemocoagulases combined with PPI could significantly improve the hemostatic efficacy of patients （P＜0.05）； there was no statistical significance in the pairwise comparison of different hemocoagulases （P＞0.05）. The optimal probabilistic ranking of network meta-analysis was as follows： Hemocoagulase agkistrodon blomhoffii combined with PPI＞ Hemocoagulase bothrops atrox combined with PPI＞Haemocoagulase agkistrodon combined with PPI＞hemocoagulase combined with PPI＞PPI alone. In terms of the incidence of adverse drug reactions （ADR）， compared with PPI monotherapy， there was no statistical difference in the incidence of ADR among four kinds of haemocoagulases combined with PPI （P＞0.05）. There was no statistical significance in the pairwise 88325750。E-mail：fengyufei@126.com comparison of different hemocoagulases （P＞0.05）. The optimal probabilistic ranking of network meta-analysis was as follows： hemocoagulase combined with PPI＞Hemocoagulase bothrops atrox combined with PPI＞Hemocoagulase agkistrodon blomhoffii combined with PPI＞Haemocoagulase agkistrodon combined with PPI＞PPI alone. CONCLUSIONS Compared with PPI monotherapy， four different sources of hemocoagulases combined with PPI have better efficacy and similar safety in the treatment of NVUGIB. There is no significant difference in efficacy and safety among different hemocoagulases.

Comparison of the effect of iRoot BP Plus and MTA on direct pulp capping of carious pulp exposed mature permanent teeth / 口腔疾病防治

Objective@#To study the clinical efficacy of biological ceramics (iRoot BP Plus ) and mineral trioxide aggregate (MTA) in direct pulp capping of mature permanent teeth, to provide referrence for clinical application.@* Methods @# Seventy-four patients with pulp exposure due to deep caries or reversible pulpitis in 75 mature permanent teeth were selected and were randomly divided into two groups. iRoot BP Plus were used as pulp capping agents in the treatment group and MTA were used as pulp capping agents in the control group respectively. The clinical efficacy and imaging analysis were performed at 1, 3, 6 and 12 months after operation. Treatment success rate of the two groups were calculated, and the influence of various factors including gender, age, tooth position, cavity, number and size of pulp exposure on the efficacy of direct pulp capping were analyzed. @* Results @#Sixty patients with 61 mature permanent teeth were selected. Twelve mouths after treatment, 61 teeth of 60 patents were completely investigated (iRoot group: 31 teeth 30 patients; MTA group: 30 teeth 30 patients). The success rates of the 2 groups were 90.3% (iRoot BP Plus) and 90.0% (MTA), respectively. There was no statistical difference between 2 groups (P>0.05). Statistical analysis also showed that gender, age, tooth position, cavity, number and size of pulp exposure had no significant difference between the two groups (P>0.05). @*Conclusion@# Both iRoot BP Plus and MTA are effective in direct pulp capping of mature permanent teeth with carious pulp exposure, while the operation of iRoot is simple and convenient.

Qiju Dihuangtang Combined with Chinese Medicine Fumigation in Treatment of Dry Eye and Its Effect on Levels of Tear IL-6 and MMP-9 / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Qiju Dihuangtang combined with Chinese medicine fumigation in the treatment of dry eye and its effect on the levels of interleukin-6 （IL-6） and matrix metalloproteinase-9 （MMP-9） in tears. MethodA total of 120 patients with dry eye of liver-kidney Yin deficiency syndrome who were treated in the Department of Ophthalmology， The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine（TCM） from october 2019 to october 2021 were randomized into the observation group and control group. The control group was given sodium hyaluronate eye drops， and the observation group was treated with sodium hyaluronate eye drops， Qiju Dihuangtang， and Chinese medicine fumigation. The treatment lasted 30 days for both groups. The changes of ocular surface disease index （OSDI）， TCM syndrome score， tear secretion （SIT）， tear film breaking up time （BUT）， corneal fluorescein staining （FL）， and tear interleukin-6 （IL-6） and matrix metalloproteinase-9 （MMP-9） were observed. ResultAfter the treatment， the total effective rate was 90.0% （54/60） in the observation group and 75.0% （45/60） in the control group （χ2=4.675， P<0.05）. After treatment， the OSDI score and TCM syndrome score were lower than those before treatment in both groups （P<0.05）， and lower in the observation group than in the control group （P<0.05）. After treatment， the SIT and BUT were higher （P<0.05） and FL score was lower （P<0.05） than those before treatment in both groups. After treatment， the improvement of the above indicators in the observation group was better than that in the control group （P<0.05）. After treatment， the levels of IL-6 and MMP-9 were lower than those before treatment in both groups （P<0.05）， and lower in the observation group than in the control group （P<0.05）. ConclusionQiju Dihuangtang combined with Chinese medicine fumigation can effectively improve subjective symptoms， promote tear secretion， prolong BUT， enhance corneal epithelial repair， and reduce the levels of tear IL-6 and MMP-9 in the treatment of dry eye.

Transcutaneous Electrical Acupoint Stimulation Combined with Warm Acupuncture for Breast Cancer Related Upper Limb Lymphedema: A Retrospective Cohort Study / 中国结合医学杂志

OBJECTIVE@#To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL).@*METHODS@#This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded.@*RESULTS@#The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group.@*CONCLUSIONS@#TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075).

Clinical efficacy of mild therapeutic hypothermia with different rewarming time on neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical efficacy of mild therapeutic hypothermia (MTH) with different rewarming time on neonatal hypoxic-ischemic encephalopathy (HIE).@*METHODS@#A prospective study was performed on 101 neonates with HIE who were born and received MTH in Zhongshan Hospital, Xiamen University, from January 2018 to January 2022. These neonates were randomly divided into two groups: MTH1 group (n=50; rewarming for 10 hours at a rate of 0.25°C/h) and MTH2 group (n=51; rewarming for 25 hours at a rate of 0.10°C/h). The clinical features and the clinical efficacy were compared between the two groups. A binary logistic regression analysis was used to identify the factors influencing the occurrence of normal sleep-wake cycle (SWC) on amplitude-integrated electroencephalogram (aEEG) at 25 hours of rewarming.@*RESULTS@#There were no significant differences between the MTH1 and MTH2 groups in gestational age, 5-minute Apgar score, and proportion of neonates with moderate/severe HIE (P>0.05). Compared with the MTH2 group, the MTH1 group tended to have a normal arterial blood pH value at the end of rewarming, a significantly shorter duration of oxygen dependence, a significantly higher proportion of neonates with normal SWC on aEEG at 10 and 25 hours of rewarming, and a significantly higher Neonatal Behavioral Neurological Assessment score on days 5, 12, and 28 after birth (P<0.05), while there was no significant difference in the incidence rate of rewarming-related seizures between the two groups (P>0.05). There were no significant differences between the two groups in the incidence rate of neurological disability at 6 months of age and the score of Bayley Scale of Infant Development at 3 and 6 months of age (P>0.05). The binary logistic regression analysis showed that prolonged rewarming time (25 hours) was not conducive to the occurrence of normal SWC (OR=3.423, 95%CI: 1.237-9.469, P=0.018).@*CONCLUSIONS@#Rewarming for 10 hours has a better short-term clinical efficacy than rewarming for 25 hours. Prolonging rewarming time has limited clinical benefits on neonates with moderate/severe HIE and is not conducive to the occurrence of normal SWC, and therefore, it is not recommended as a routine treatment method.

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.

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.

Clinical observation on electroacupuncture at "four points of sacral region" on moderate to severe stress urinary incontinence after radical prostatectomy / 中国针灸

OBJECTIVE@#To compare the clinical therapeutic effect between electroacupuncture at "four points of sacral region" and transurethral Erbium laser in treatment of moderate to severe stress urinary incontinence after radical prostatectomy.@*METHODS@#A total of 68 patients of moderate to severe stress urinary incontinence after radical prostatectomy were divided into an electroacupuncture group (34 cases) and an Erbium laser group (34 cases, 3 cases dropped off) according to the settings. In the electroacupuncture group, electroacupuncture was applied at "four points of sacral region", i.e. points of 0.5 cun beside bilateral sacrococcygeal joints and bilateral Huiyang (BL 35), with continuous wave, 2 Hz in frequency, 60 min each time, once every other day, 3 times a week, 12 times as one course of treatment. In the Erbium laser group, transurethral Erbium laser technology was given, once every 4 weeks as one course of treatment. Both groups were treated for 5 courses. The scores of the International Consultation on Incontinence questionnaire-short form (ICI-Q-SF) and the incontinence quality of life questionnaire (I-QOL) were observed before treatment, after each course of treatment and in follow-up after 1 and 2 months of treatment completion, respectively, and the clinical efficacy was evaluated after treatment in the two groups.@*RESULTS@#Compared with those before treatment, the ICI-Q-SF scores were decreased while the I-QOL scores were increased after 5 courses of treatment and in follow-up after 1, 2 months of treatment completion in the two groups (P<0.01). The ICI-Q-SF score in follow-up after 2 months of treatment completion were higher than that after 5 courses of treatment in the Erbium laser group (P<0.05). After 3, 4, 5 courses of treatment and in follow-up after 1 and 2 months of treatment completion, the ICI-Q-SF scores in the electroacupuncture group were lower than those in the Erbium laser group (P<0.05, P<0.01); after 2, 3, 4, 5 courses of treatment and in follow-up after 1 and 2 months of treatment completion, the I-QOL scores in the electroacupuncture group were higher than those in the Erbium laser group (P<0.01). The change ranges of ICI-Q-SF score and I-QOL score between before treatment and after each course of treatment in the electroacupuncture group were lager than those in the Erbium laser group (P<0.01, P<0.05). The total effective rate was 61.8% (21/34) in the electroacupuncture group, which was superior to 19.4 (6/31) in the Erbium laser group (P<0.01).@*CONCLUSION@#Both electroacupuncture at "four points of sacral region" and transurethral Erbium laser can improve the clinical symptoms and the quality of life in patients of moderate to severe stress urinary incontinence after radical prostatectomy. The short-term efficacy and long-term efficacy of electroacupuncture are superior to the Erbium laser technology.