Wumei Pills, a classic traditional Chinese medicine(TCM) formula, are widely used in the treatment of biliary ascariasis and diarrhea. In recent years, studies have shown that Wumei Pills have advantages in the treatment of type 2 diabetes mellitus(T2DM), while there are no relevant reports that systematically evaluate the efficacy of Wumei Pills in the treatment of T2DM. This study addresses this issue by systematically evaluating the efficacy and safety of Wumei Pills, aiming to provide an evidence-based basis for clinical practice. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, and VIP were researched for the randomized controlled trial(RCT) involving Wumei Pills for the treatment of T2DM that were published from inception to September 2024. RevMan 5.3 was used for the Meta-analysis of the data. A total of 18 RCTs were included, with a total of 1 437 patients. Meta-analysis produced the following results.(1)Treatment group outperformed control group in terms of overall response rate(RR=1.28, 95%CI[1.14, 1.43], P<0.000 1), fasting blood glucose(FPG)(WMD=-0.69, 95%CI[-0.93,-0.46], P<0.000 01), two-hour postprandial plasma glucose(2hPG)(WMD=-0.74, 95%CI[-1.17,-0.31], P<0.000 7), glycated hemoglobin(HbA1c)(WMD=-0.39, 95%CI[-0.60,-0.18], P=0.000 3), high-density lipoprotein(HDL)(WMD=0.38, 95%CI[0.28, 0.48], P<0.000 01), and body mass index(BMI)(WMD=-1.41, 95%CI[-2.40,-0.42], P=0.005).(2)The two groups had comparable effects regarding total cholesterol(TC)(WMD=-0.53, 95%CI[-1.13, 0.08], P=0.09) and low-density lipoprotein(LDL)(WMD=-0.25, 95%CI[-0.56, 0.06], P=0.12).(3)Triglycerides(TG)(WMD=-0.28,95%CI [-0.59,0.03],P=0.08), sensitivity analysis showed potential reduction effect(WMD=-0.20,95%CI[-0.36,-0.04],P=0.01). Occurrence of adverse drug reaction(RR=0.43,95%CI [0.23,0.80],P=0.007), sensitivity analysis showed significant disappearance(RR=0.56,95%CI[0.26,1.22],P=0.14), suggesting that the efficacy of treatment group was not better than that of control group. The results indicate that the treatment of T2DM with Wumei Pills is greatly related to the improvement of glucose metabolism, lipid metabolism, and clinical efficacy. The findings provide a basis for clinical application of Wumei Pills in treating T2DM, while the conclusion remains to be verified by clinical studies with higher quality.
Humans ; Diabetes Mellitus, Type 2/blood* ; Drugs, Chinese Herbal/administration & dosage* ; Randomized Controlled Trials as Topic ; Blood Glucose/metabolism* ; Hypoglycemic Agents/therapeutic use* ; Treatment Outcome ; Glycated Hemoglobin/metabolism* ; Female

OBJECTIVE: To explore the application effectiveness of multidisciplinary team (MDT) in the diagnosis and treatment of chronic refractory wounds, and to provide new ideas for optimizing the clinical diagnosis and treatment of such diseases. METHODS: A retrospective analysis was performed on the clinical data of patients with chronic refractory wounds who underwent surgery at Peking University Third Hospital from January 2015 to October 2023, and a total of 456 patients, including 290 males and 166 females, with an average age of (49.4±16.9) years. According to whether preoperative MDT discussion was conducted, the patients were divided into MDT discussion group and non-MDT discussion group. The overall implementation process of MDT included: Starting and recording with the medical office, collecting data and discussing the initial MDT, informing the patient of the treatment plan and strictly implementing it, and the change of the condition needs to be discussed again by MDT. The general clinical data, anesthesia risk grade, complications (hypertension, diabetes, coronary heart disease), and the etiology and location of chronic refractory wounds between the two groups were compared. The main observational measurements and outcome indicators of treatment effectiveness included the number of surgeries required to achieve wound healing after admission, the recurrence rate after wound healing, the incidence of perioperative complications (pulmonary infection, severe cardiovascular event, vein thrombus embo-lism, cerebral stroke and delirium, etc.), and patient satisfaction score. RESULTS: There were 189 patients in the MDT discussion group and 267 patients in the non-MDT discussion group. There was no significant statistical difference in the clinical data, such as age, gender, body mass index, American Society of Anesthesiologists, comorbidities, etiology, and location of chronic refractory wounds between the two groups (P>0.05). The average number of surgeries required for wound healing in MDT discussion group and non-MDT discussion group was 2.1±1.1 and 2.8±1.6, respectively, with a statistically significant difference (P < 0.001). This difference was also significant in chronic refractory wounds caused by three etiologies: Diabetic ulcer, infection after trauma or surgery, and non-union after radiotherapy (P < 0.05). The recurrence rate of the patients in the non-MDT discussion group after wound healing was 18.0%, slightly higher than that in the MDT discussion group of 14.3% (P>0.05). In terms of perioperative complications, the non-MDT discussion group also had a higher incidence (3.7% vs. 2.6%), but the difference was not statistically significant (P>0.05). In terms of patient satisfaction, the MDT discussion group scored significantly higher (96.5 vs. 91.1, P=0.028). CONCLUSION The MDT mode can significantly reduce the number of surgeries for patients with chronic refractory wounds, improve the effectiveness of therapy and increase patient satisfaction. It is a recommended model for optimizing the clinical diagnosis and treatment effectiveness of chronic refractory wounds.
Humans ; Patient Care Team ; Retrospective Studies ; Chronic Disease ; Male ; Female ; Middle Aged ; Wound Healing ; Aged ; Adult ; Wounds and Injuries/surgery*

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

The changes in epigenetic modifications of histones are one of the important factors in cancer development and metastasis,and the development of epigenetic therapies for cancer treatment has led to epigenetic drug screening as a research focus. In this work,the common methylation and acetylation modifications at the N-terminal of cellular histones H3 were quantified by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method,and a throughput assay for screening and assessment of epigenetic drug was established. A total of 39 kinds of modification combinations containing common methylation and acetylation sites of H3 peptides were simultaneously monitored by triple quadrupole mass spectrometry in multiple reaction monitoring (MRM) mode. The developed method was applied to analyze HepG2 cells exposed for 24 h to 28 kinds of epigenetic drugs that could modulate the level of methylation or acetylation modifications. Results showed that 25 of these drugs,such as deacetylase inhibitors Abexinostat,Valproic acid and AGK7,induced histone H3 modification changes in the exposed cells that were consistent with those reported in the literature,while other modification changes were also detectable. Three of these drugs,including demethylase inhibitors IOX1,GSK-j1 and acetyltransferase inhibitor L002,however,induced modification changes different from those reported in the literature. An overall test match rate of 89.3％ was achieved. The established LC-MS/MS method could quantitatively analyze histone H3 modification sites and their changes in cells in a high-throughput and highly sensitive manner,and could be applied to the evaluation of epigenetic drugs with known activities,with good specificity and rich modification information,which was expected to provide a new technological tool for screening and evaluation of epigenetically active compounds and exploration of their mechanism of action.

Objective To explore the mediating effect of sleep duration on the relationship between qi stagnation constitution and anxiety/depression in junior high school students.Methods From March 20 to March 31,2020,a total of 10,325 students from 6 junior high schools in Henan,Liaoning,Shaanxi,Shandong,and Fujian provinces were sampled by cluster sampling.Firstly,the general conditions(age,gender,grade,hometown,whether they are an only child)and sleep duration were collected,and their qi stagnation constitution,depression and anxiety status were evaluated by using the Qi Stagnation Subscale in the"TCM Constitution Classification and Judgment Scale",the Patient Health Questionnaire(PHQ-9)and the Generalized Anxiety Disorder(GAD-7).Secondly,Spearman correlation analysis was used to explore the correlation between qi stagnation constitution,sleep duration,and anxiety/depression.Then,linear regression analysis and mediating effect test were used to explore the relationship between qi stagnation constitution and anxiety/depression in junior high school students,and the mediating effect of sleep duration was analyzed,and the results were verified.Results(ⅰ)The detection rate of anxiety in non-only children was higher than that of only children(x2=11.198,P=0.001);The detection rate of anxiety(x2=106.967,P＜0.001)or depression(x2=84.692,P＜0.001)was higher among senior students than those in lower grades,while those of girls with anxiety(x2=100.441,P＜0.001)or depression(x2=71.418,P＜0.001)were higher than those of boys.The detection rates of anxiety(x2=1 092.298,P＜0.001)and depression(x2=866.740,P＜0.001)in qi stagnation constitution students were higher than those of non-qi stagnation constitution students,and the detection rates of anxiety(x2=1 076.716,P＜0.001)and depression(x2=1 099.725,P＜0.001)in students whose sleep duration less than 8 h were higher than those of whose sleep duration more than 8 h,and the shorter the sleep duration,the higher the detection rate.(ⅱ)Qi stagnation constitution positively predicted anxiety/depression(β=0.679,P＜0.001;β=0.718,P＜0.001),and sleep duration had a negative predictive effect on anxiety/depression(β=-0.403,P＜0.001;β=-0.439,P＜0.001).(ⅲ)Sleep duration played a partial mediating role in the relationship between qi stagnation constitution and anxiety/depression in junior high school students,and the mediating effect accounted for 13.40％and 13.79％of the total effect,respectively.Conclusion Although qi stagnation constitution mainly affects anxiety/depression through direct effect,it can still be partially indirectly realized through the mediating variable of sleep duration,that is,the shorter the sleep duration,the higher the risk of anxiety/depression in junior high school students.Therefore,the mental health problems of junior high school students can be prevented and improved by regulating qi stagnation constitution and ensuring adequate sleep duration.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.