Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective To investigate the therapeutic effects and mechanisms of Maxing Shigan Decoction on cough variant asthma(CVA)rats.Methods Sixty rats were randomly divided into normal group,model group,low and high dose groups of Maxing Shigan Decoction,and high-dose of Maxing Shigan Decoction + signal transducer and activator of transcription 3(STAT3)activator Colivelin(Col)group,12 rats in each group.Except for the normal group,the CVA model was constructed by intraperitoneal injection of ovalbumin combined with moxa fumigation in all other groups of rats.After the corresponding treatment,the rats were observed for signs and cough counts,airway resistance(RE)was detected by pulmonary function meter,eosinophils(EOS)were counted by Diff-Quik staining,histopathological features of the lungs and bronchial tubes were observed by hematoxylin-eosin(HE)staining method,and the lung tissues were detected by enzyme-linked immunosorbent assay(ELISA)for monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α),and the protein expression levels of interleukin 6(IL-6),STAT3,and transient receptor potential vanilloid-1 channel(TRPV1)were detected by Western Blot.Results Compared with the normal group,rats in the model group showed obvious asthma symptoms,severe inflammatory cell infiltration was seen in the lung tissue,bronchial epithelial cell necrosis,ciliated adhesion,mucus,and RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,TRPV1 were elevated(P＜0.05);compared with the model group,rats in the low-and high-dose groups of Maxing Shigan Decoction showed significant improvement in asthma symptoms,reduction in lung and bronchial injury,and dose-dependent reduction in RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P＜0.05);compared with the high-dose group of Maxing Shigan Decoction,the rats in the high-dose Maxing Shigan Decoction+Col group showed increased asthma,increased lung and bronchial injury,and increased RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P＜0.05).Conclusion Maxing Shigan Decoction can effectively improve cough variant asthma in rats,and its mechanism is related to the inhibition of IL-6/STAT3 signaling pathway and the high expression of TRPV1.

ObjectiveTo analyze the clinical characteristics and the use of traditional Chinese medicine （TCM） therapy in cancer patients with COVID-19， and to provide reference for making TCM prevention and treatment strategies and determining diagnosis and treatment priorities for patients with malignant tumors in the COVID-19 epidemic. MethodsThe medical records of 225 malignant tumor cases with COVID-19 who were admitted to 7 national research centers from January 1st to 20th， 2023 were retrospectively collected， and the main symptoms and duration after infection， nucleic acid negative conversion time， use of TCM therapy， and changes in adverse reactions after resuming anti-tumor treatment were analyzed. ResultsA total of 222 malignant tumor patients with COVID-19 were included in the analysis， involving 205 mild cases and 17 moderate cases. The top four most frequently reported clinical symptoms were fever （165 cases）， expectoration or dry cough （99 cases）， decreased appetite （95 cases） and fatigue （85 cases）， of which 40 expectoration or dry cough cases ， 37 fatigue cases and 29 decreased appetite cases lasted for more than 14 days. One hundred and five patients with nucleic acid detection report had a median negative conversion time of 14 days. The nucleic acid negative conversion time was significantly longer in patients with lung cancer compared to those with digestive system malignant tumors， and in those with myelosuppression than those without （P＜0.01）. During the infection period， 47.30% （105/222） of the patients used Chinese patent medicine， and 21.17% （47/222） were treated with herbal decoctions. The use of TCM in patients during the prevention and rehabilitation period， was 1.80%（4/222） and 7.21%（16/222）， respectively. Fifty-five patients resumed anti-tumor treatment after nucleic acid negative conversion， and received TCM simultaneously. Observed adverse reactions， including gastrointestinal reactions， bone marrow suppression， and neurotoxicity， were all grade 1 to 2， and no new adverse events occurred during follow-up. ConclusionCertain malignant tumor patients with COVID-19 had prolonged symptoms and nucleic acid negative conversion time Rational use of TCM can help to promote the rehabilitation of the patients and ensure the smooth process of anti-tumor treatment after infection.

Objective:To evaluate the robustness of fully automated adaptive planning for Ethos online adaptive radiotherapy (ART) based on the intelligent optimization engine (IOE).Methods:Clinical data of 11 stage ⅠB cervical cancer patients admitted to Peking Union Medical College Hospital between June 2021 and June 2022 were retrospectively analyzed. Original planning images and iterative cone-beam computed tomography (iCBCT) images of each radiotherapy treatment were acquired, and all patient data were imported into the Ethos simulator. IOE-based 9-field automatic plan generation was performed for 11 patients using Ethos, and the generated plans were sent to online adaptive radiotherapy simulation to obtain each online adaptive radiotherapy plan (273 fractions in total) and complete the simulated treatment. For comparison, manual plan design was performed based on the images and contoured structures used for online adaptive radiotherapy planning, and the manually plans created with evenly divided 9 fields. Dosimetric parameters, plan complexity parameters, and Mobius quality assurance (QA) pass rates were collected to compare and evaluate the robustness of the online adaptive radiotherapy plan in terms of organs at risk (OAR), target volume dosimetric parameters, and plan complexity by using paired t-test or rank sum test. Results:The online adaptive plan of cervical cancer had comparable planning target volume (PTV) coverage compared to the manual plan. For the clinical target volume (CTV) D 99%, online adaptive plan was significantly higher than the manual plan [(45.93±0.36) vs. (45.32±0.31) Gy, P<0.001]. For hot dose area, the maximum point dose (PTV D max) of adaptive plan was significantly higher than the manual plan [(49.89±1.25) vs. (48.48±0.77) Gy, P<0.001], but the PTV D 1% of adaptive plan was significantly lower than the manual plan [(47.22±0.29) vs. (47.59±0.48) Gy, P<0.001]. There was no statistical difference in the conformal index ( P=0.967). And there was significant difference in the homogeneity index, with same medians and less dispersion in adaptive plan ( P<0.001). For OAR dose, bladder D mean, rectal V 40 Gy, small intestine D mean of adaptive plan was slightly higher than that of the manual plan; the rectal D mean, small intestine D 2 cm3 of the adaptive plan was slightly lower than that of manual plan; dosimetric parameters of right and left femoral heads, spinal cord and bone marrow of the adaptive plan were better than those of manual plan. The adaptive plan had more monitor units (MU) than the manual plan, but the complexity of the adaptive plan was significantly lower than that of the manual plan (0.135±0.012 vs. 0.151±0.015, P<0.001). For Mobius γ pass rate (5%/3 mm), both adaptive and manual plans met clinical requirements. Conclusion:Ethos cervical cancer online adaptive plan, which is based on the IOE engine, demonstrates good robustness and ensures the quality of online adaptive plans generated for each treatment fraction.

Objective:To evaluate the automatic optimization performance and clinical feasibility of the intelligent optimization engine (IOE) in the Ethos online adaptive radiotherapy platform.Methods:Clinical data of 11 patients with postoperative cervical cancer treated with Halcyon accelerator were retrospectively analyzed. Manual planning was performed for all patients using the 4 full arc volumetric modulated arc therapy (VMAT) (Manual-4Arc) in Eclipse, with a prescription dose of 45 Gy/25F. Patient images and structures were imported into the Ethos simulator, and appropriate clinical goals were added based on clinical requirements. The target coverage was normalized to 95%. Automatic plan generation was conducted using IOE, resulting in 7, 9, and 12 field intensity modulated radiotherapy (IMRT) plans (IMRT-7F、IMRT-9F、IMRT-12F), as well as 2 and 3 arc VMAT plans (VMAT-2Arc、VMAT-3Arc). Dosimetric index comparisons were made between the Manual-4Arc plans and the 5 groups of IOE-generated plans through one-way analysis of variance. Based on the analysis results, Turky post hoc multiple comparisons were performed to evaluate the automatic optimization performance of IOE.Results:In terms of the high dose area, the IMRT-12F plans showed the lowest D 1% for the planning target volume (PTV), and there were significant differences compared to the Manual-4Arc plans ( P=0.004). Regarding target coverage, all groups produced clinical target volume (CTV) plans that met the clinical requirements. Although the Ethos online adaptive plans were normalized during planning, the PTV coverage was slightly insufficient. For organs at risk (OAR) close to the target, such as the bladder, there were significant differences in V 30 Gy, V 40 Gy, and D mean among the 6 groups of plans. The dose ranking for the bladder was generally as follows: IMRT-12F

The disorder of group 3 innate lymphoid cells(ILC3)subgroup,such as the predominance of NCR-ILC3 but the deple-tion of NCR+ILC3,is unfavorable to damaged intestinal barrier repair,which leads to the prolongations and obstinacy of ulcerative colitis(UC).Our previous studies had shown that luteolin promoted NCRILC3 differentitating into NCR+ILC3 to improving the de-pletion of NCR+ILC3 in UC mice,while the mechanism is unclear.This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3.UC mice model was established with 2％DSS and Notch signaling was blocked,then luteolin was used to intervene.The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice,including inhibit-ing the weight loss,reducing the pathological damage of colon mucosa,etc.,was diminished with blocking Notch signaling pathway.In addition,luteolin increased the proportion of NCR+ILC3,NCR+MNK3 and IL-22+ILC3,decreased intestinal permeability,pro-moted mucin secretion,and promoted ZO-1 and Occludin expression,the above effect of luteolin was neutralized by Notch inhibitor LY-411575.Luteolin activated the abnormally blocked Notch signaling pathway in UC mice.And molecular docking predicted the af-finity of luteolin for RBPJ to be-7.5 kcal·mol-1 in mouse,respectively;the affinity of luteolin for Notchl and RBPJ was respectively scored to be-6.4 kcal·mol-1 and-7.7 kcal·mol-1 homo sapiens.These results proved that luteolin is positive for enhancing the propor-tion of NCR+ILC3 via Notch signaling,and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alle-viating ulcerative colitis.

Objective:To retrospectively analyze and summarize the clinical experience and therapeutic effect of anterograde Needle-perc combined with RIRS, namely N+ R (Needle perc + RIRS) technique in the treatment of complex calyceal diverticular stone.Methods:Retrospective analysis of 23 cases of complex renal caliceal diverticulum stones admitted to our hospital from January 2020 to December 2022. The complex factors mainly include the invisible cervical orifice of diverticulum, large stone volume, and special anatomical location, which makes single RIRS or PCNL treatment difficult or unsuccessful. There were 14 males and 9 females with an average age of (42.3±6.1) years. Three cases were upper calyceal diverticular stone, average size was (0.9±0.2)cm. Nine patients had diverticular stone in the middle posterior calyx, and the average size was (1.2±0.3)cm. The average size of four diverticular stone was (1.8±0.2)cm in the anterior middle calyx. Seven patients had diverticular stone with an average size of (1.3±0.1)cm in lower calyx. Among them, 12 patients underwent RIRS which were difficult or stone undiscovered, and 3 patients underwent PCNL and the operation was terminated due to failure of channel establishment. In our center, oblique supine lithotomy position (male) or prone split-leg position (female) was adopted, and the combined treatment of Needle-perc and RIRS was performed. Needle-perc puncture was completed under the guidance of full ultrasound. During the operation, methylene blue reagent or mutual guidance of two endoscopes was used to find the diverticulum neck and expand the outlet with holmium laser incision. Depending on the size and location of the stones, a single Needle-perc laser lithotripsy combined with stone removal in flexible ureteroscope was used, or dual lasers were be used simultaneously for stone removal under double endoscopes. The first stage stone free rate, operation time, hemoglobin decrease, complications, postoperative hospital stay and other conditions were analyzed.Results:All the 23 operations were completed successfully. The stone free rate within 48 hours and one month after surgery was 78.2% and 100.0% respectively. The average operation time was (61.5±12.2)min. The mean postoperative hospital stay was (2.8±0.6) days. The mean decrease of hemoglobin was (3.6±0.4)g/L. Three patients had fever and one patient had renal subcapsular effusion. After anti-inflammatory and symptomatic treatment, the patient was discharged. There was no incidence of Clavien-Dindo≥Ⅱcomplications such as blood transfusion, abdominal organ injury or urosepsis.Conclusions:Treatment of complex renal caliceal diverticulum stones using N+ R technique of anterograde needle-perc combined with RIRS can effectively improve the success rate of first-stage surgery. Overall, it is safe, efficient and feasible with the advantages of high stone free rate, lower damage, and few postoperative complications.