OBJECTIVE: To study the clinical efficacy of Wenyang Lishui Formula (WYLSF) in preventing ovarian hyperstimulation syndrome (OHSS) and explore the suitable range of estradiol (E₂) on the human chorionic gonadotropin (HCG) day in patients with OHSS using WYLSF. METHODS: Part I: eligible patients at high risk for OHSS undergoing ovulation induction between January and December, 2023 were randomized into 2 groups based on the actual treatment. The treatment group received 200 mL WYLSF formula twice daily for 5 days after oocyte retrieval in a combination of lifestyle coaching (LC) intervention including regular diet and exercise, whereas the LC group received LC intervention alone. The incidence of OHSS, OHSS self-assessment scales, changes in E₂ levels on HCG day and 5 days after oocyte retrieval, ovarian morphology changes, and menstrual recovery were compared between the two groups. Part II: patients at high risk for OHSS treated with WYLSF were studied. The optimal E₂ threshold on the HCG day was determined using the maximum selection test, and a multivariate analysis was adopted to compare the relationship between different E₂ levels on HCG day and hospitalization rate, incidence of moderate to severe OHSS, and self-assessment scales, to explore the preventive effect of WYLSF on OHSS in patients with varying E₂ levels. RESULTS: A total of 120 patients were included in the Part I analysis. The treatment group (60 cases) showed a significant reduction in the incidence, duration, and severity of abdominal distension, as well as the incidence of vomiting compared with the LC group (P<0.05). The post-retrieval E₂ levels in the treatment group decreased significantly more (P=0.032). Among 1,652 patients treated with WYLSF in the Part II, 90 patients with ⩽ 10092 pmol/L, 159 with >31074 pmol/L, and 1,403 in the middle range group were formed based on E₂ levels on HCG day in Part two analysis. Univariate and regression analyses showed that patients with E₂ levels >31073 pmol/L had a significantly higher incidence of moderate to severe OHSS compared to those with E₂ levels ⩽ 10092 pmol/L (P<0.05). CONCLUSIONS WYLSF can effectively reduce specific symptoms in high-risk OHSS patients after ovulation induction and significantly lower E₂ levels. It may be more suitable for high-risk OHSS patients with E₂ levels <31073 pmol/L on HCG day. (Registration No. MR-11-23-032493, https://www.medicalresearch.org.cn/login ).
Humans ; Ovarian Hyperstimulation Syndrome/blood* ; Female ; Adult ; Prospective Studies ; Drugs, Chinese Herbal/pharmacology* ; Estradiol/blood* ; Ovulation Induction ; Chorionic Gonadotropin

The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for cancer chemoimmunotherapy. However, only few drugs or treatment modalities can trigger an ICD response and none of them exert a considerable clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic response are required. In this study, five new cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed and synthesized. Among them, Ir-1 exhibited the highest in vitro cytotoxicity. Mechanistically, Ir-1 could trigger autophagy-dependent ferroptosis and a subsequent ferroptosis-dependent ICD response as well as indoleamine 2,3-dioxygenase (IDO) inhibition via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in MDA-MB-231 cells. When immunocompetent BALB/c mice were vaccinated with Ir-1-treated dying TNBC cells, antitumor CD8⁺ T-cell response and Foxp3⁺ T-cell depletion were induced, resulting in long-lasting antitumor immunity in TNBC cells. Moreover, combination therapy with Ir-1 and anti-PD1 could substantially augment in vivo therapeutic effects. Based on these results, Ir-1 is a promising candidate for chemoimmunotherapy against TNBC and its effects are mediated synergistically via ICD induction and IDO blockage.

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

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

ObjectiveTo establish a method for the determination of 1,1,1,2-tetrachloroethane (TeCA) and 1,1,2,2-TeCA in human urine using liquid-liquid extraction-gas chromatography. Methods The 5.0 mL urine sample was mixed with 2.0 g anhydrous sodium sulfate and 5.0 mL ethyl acetate, then vortexed mixing. The 1.0 mL extraction was separated by 100% dimethylpolysiloxane capillary gas chromatography column, detected by flame ionization detector, and quantified by an external standard method. Results The linear ranges of 1,1,1,2-TeCA and 1,1,2,2-TeCA were 0.250-50.750 mg/L, with both correlation coefficients of >0.999 9. The detection limit of 1,1,1,2-TeCA in urine was 0.020 mg/L, and the lower limit of quantification was 0.060 mg/L. The average recovery was 88.02%-101.32%, and the within-run and between-run relative standard deviations (RSDs) were 0.11%-0.47% and 0.39%-1.09%, respectively. The detection limit of 1,1,2,2-TeCA in urine was 0.050 mg/L, and the lower limit of quantification was 0.150 mg/L. The average recovery was 93.42%-101.32%, and the within-run and between-run RSDs were 0.28%-1.04% and 0.50%-1.03%, respectively. Both the 1,1,1,2-TeCA and 1,1,2,2-TeCA cannot be stored at room temperature. The 1,1,2,2-TeCA can be stored at 4 ℃ for at least three days. At -20 ℃, the 1,1,1,2-TeCA can only be stored for one day, while 1,1,2,2-TeCA can be stored for at least five days. Conclusion This method has high sensitivity, good specificity, simple sample pretreatment, and more intuitive and reliable results. It can be used to determine the level of 1,1,1,2-TeCA and 1,1,2,2-TeCA in urine of occupational population.

Objective: To establish a solvent desorption-gas chromatography method for the determination of 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane in workplace air. Methods: The 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane in workplace air were collected using activated carbon tubes, desorbed with carbon disulfide, and separated and detected by gas chromatography. The quantifications were based on standard curves. Results: The linear ranges of 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane were 0.98-395.50 and 0.87-395.50 mg/L, respectively, with the correlation coefficient of 0.999 95. The detection limits were 0.29 and 0.26 mg/L, respectively. The average of desorption efficiency was 92.04%-104.67%. The within- and between-run relative standard deviations were 1.42%-2.09% and 1.63%-6.09%, respectively. The sampling efficiency was more than 98.00%. The samples could be stored at room temperature for at least 14 days. Conclusion: This method can be used in detection of 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane in workplace air.

Objective:To explore the clinical effect of laparoscopic anatomical hepatic segment Ⅷ (S8) resection.Methods:Of 16 patients with liver cancer who underwent laparoscopic anatomical hepatic S8 resection at the National Cancer Center from October 2020 to October 2022 were were enrolled, including 13 males and 3 females, aged (59.1±10.9) years. The operation time, intraoperative blood loss, occurrence of intraoperative blood transfusion, and postoperative complications were retrospectively analyzed. Recurrence and survival were followed up by outpatient and telephone reviews.Results:Laparoscopic anatomical hepatic S8 resection was successfully performed in 16 patients without conversion to laparotomy. Among them, 10 patients underwent the intraoperative ultrasound guided hepatic parenchymal approach, and 6 underwent laparoscopic Glissonean pedicle puncture for the positive staining of S8 using indocyanine green. The operation time was (274.8±82.8) min, and the intraoperative blood loss was [ M( Q1, Q3)] 100.0 (50.0, 200.0) ml. There were no intraoperative blood transfusion or postoperative complication. The drainage tube was successfully removed and the patients were discharged 5 to 7 days after surgery. The patients were followed up for 5 to 24 months and all survived. Two patients had tumor recurrence. Conclusion:Laparoscopic anatomical S8 resection is safe and feasible.

Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ²=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ²=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ²=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.
Male ; Female ; Child ; Humans ; Child, Preschool ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Retrospective Studies ; Survival Analysis ; Mutation ; Hematopoietic Stem Cell Transplantation

Objective To establish a high performance liquid chromatography (HPLC) method for simultaneous determination of six aniline compounds (ADs) in workplace air. Methods GDH-1 air sampling tube was used to collect six co-existing ADs such as aniline, o-toluidine, N-methylaniline, m-methylaniline, p-methylaniline and N,N-dimethylaniline in the vapor and aerosol of workplace air. The samples were desorbed and eluted using a methanol solution containing 1.00% ammonia water, followed by separation on a C₁₈ chromatographic column and detection using a diode array detector. Results The quantification range of the method was 0.19 -253.50 mg/L, with the correlation coefficient of 0.999 9 for all six ADs. The minimum detection range was 0.02-0.06 mg/m³, and the minimum quantitation range was 0.04-0.19 mg/m³ [both calculated for a 15.0 L sample with a desorption (elution) solution volume of 3.00 mL]. The average desorption and elution efficiencies were 92.15%-104.41% (silica gel) and 94.29%-104.29% (filter membrane). The intra-assay relative standard deviation (RSD) ranged from 0.90%-9.72% (silica gel) and 0.57%-6.96% (filter membrane). The inter-assay RSD ranged from 2.03%-9.78% (silica gel) and 2.50%-8.62% (filter membrane). The samples were stable at room temperature for seven days. Conclusion This method can be used for the simultaneous determination of six ADs in workplace air.