Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVE: Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. METHODS: HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. RESULTS: Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. CONCLUSION Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis. Please cite this article as: Feng CY, Cai CS, Shi XQ, Zhang ZJ, Su D, Qiu YQ. Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma. J Integr Med. 2025; 23(1): 79-91.
Humans ; MicroRNAs/genetics* ; Liver Neoplasms/metabolism* ; Carcinoma, Hepatocellular/metabolism* ; Mitophagy/drug effects* ; Resveratrol/pharmacology* ; Animals ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Hep G2 Cells ; Mice ; Disease Progression ; Mice, Inbred BALB C

Objective To explore the utility of different endoscopic retrograde cholangiopancreatography(ERCP)complexity scales in the training of endoscopists.Methods Clinical data of 237 patients treated by ERCP completed by trainee physicians at two hospitals in Eastern China from February 2022 to February 2023 were prospectively collected.All ERCP cases were classified using previously proposed complexity grading scales,including the American Society of Gastrointestinal Endoscopy(ASGE),Morriston and HOUSE grading scales,compared with the hepatopancreatic ampulla features classification.Successful intubation,successful surgical treatment and complication rates within 48 h were recorded.Results Within each grading,subgroups were divided according to severity,and the comparison of intubation success rates between subgroups in the 3 different grades showed statistically significant differences(P = 0.000).The treatment success rate and intubation success rate had similar findings(P = 0.000).There was no correlation between the complication rate and ASGE grading(P = 0.361),Morriston grading(P = 0.332),and HOUSE grading(P = 0.586).When only cases with primitive papillae were considered,the intubation success rate depended on the complexity grading after the newly added classification of hepatopancreatic ampulla features.In the ASGE group,the success rate of intubation was compared between different subgroups,and the difference was statistically significant(P = 0.004);in the Morriston group,the success rate of intubation was compared between different subgroups,and the success rate of intubation was statistically significant(P = 0.002);in the HOUSE group,the success rate of intubation was compared between different subgroups,and the difference was statistically significant(P = 0.000);In the hepatopancreatic ampulla characteristics group,the difference in intubation success rate was statistically significant when compared between different subgroups(P = 0.000).Similar findings were also found for treatment success rate and intubation success rate(P = 0.000).There was no correlation between the complication rate and ASGE group(P = 0.586),Morriston group(P = 0.443),HOUSE group(P = 0.306),and hepatopancreatic ampulla characteristics group(P = 0.350).Conclusion The use of hepatopancreatic ampulla features as a classification of biliary cannulation complexity is feasible and could be an alternative or additional means of predicting successful biliary cannulation and surgical treatment success and could be used in the future to assess endoscopist training and learning progress and technical standards.

In view of the problem of slow development of intensive care medicine in Xizang, the research team made full use of the national partner assistance to Xizang, gathered resources across all cities in Xizang, and formed a national academic platform for critical care medicine in plateau areas. Adhering to the academic orientation with hemodynamics as the main topic, critical care ultrasound as the bedside dynamic monitoring and evaluation method, and blood flow-oxygen flow resuscitation as the core connotation, we have achieved the goals of improving the critical care talent echelon throughout Xizang, driving the overall progress of intensive care medicine in Xizang, making a figure in China, and focusing on training of top-notch talents.

Objective:To investigate the clinical characteristics and prognosis of pancreatic acinar cell carcinoma (PACC).Methods:A retrospective case-control study analysis was conducted on the clinical data of 15 PACC patients admitted to Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University from June 2010 to May 2023. The clinical features and prognosis were analyzed.Results:Among the 15 patients with PACC, there were 9 males and 6 females, with a median age of 56 years, age ranged from 34 to 78 years. Abdominal pain was the initial symptom in 80.0% (12/15) of patients. Only 3 patients had elevated serum alpha-fetoprotein or carbohydrate antigen 19-9 levels. 80.0% (12/15) of the tumors were located in the pancreatic head, with an mean maximum diameter was (5.85±3.27) cm. CT scans showed heterogeneous enhancement in all patients, with cystic changes observed in 10 patients′ tumors. 7 patients underwent surgical treatment, including 1 patient involving venous resection and 2 patients involving partial gastrectomy; postoperative staging revealed that stage IB in 3 patients, IIA in 3 patients, and stage Ⅲ in 1 patient. Immunohistochemistry showed that there were 5 cases of Syn (+ ), 3 cases of CgA (+ ), 2 cases of AFP (+ ), 7 cases of Trypsin (+ ), 2 cases of CK7 (+ ), 2 cases of CK19 (+ ), 7 cases of β-catenin (+ ) and 2 cases of CD56 (+ ). Treatment after surgery included adjuvant chemotherapy for all surgical patients. 4 patients received systemic therapy, while 4 patients did not receive any treatment. Follow-up was completed for 11 patients, and lost in 4 patients; among the 7 patients who underwent surgical resection, 3 patients died with an average survival time of 44 months, ranged from 24 to 74 months, while the remaining 4 patients were alive with an average follow-up time of 26 months, ranged from 14 to 38 months. Among the 4 patients treated with systemic therapy, the average survival time was 16 months, ranged from 2 to 41 months.Conclusions:PACC is a rare pancreatic tumor that mainly affects elderly men. Clinical symptoms are often atypical, and there are no specific serum markers. The characteristic imaging findings include uneven enhancement with cystic changes, and positivity for trypsin on immunohistochemistry. Surgical resection combined with adjuvant therapy can provide long-term survival for patients, while those with distant metastasis have a poorer prognosis.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.
Humans ; Dermatitis, Atopic/drug therapy* ; Quality of Life ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.
Humans ; Dermatitis, Atopic/drug therapy* ; Quality of Life ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome