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

ObjectiveTo investigate the accuracy of multiple discriminant analysis （MDA） versus fibrosis-4 （FIB-4） in assessing liver fibrosis degree in patients with HBV infection， as well as the possibility of MDA as an indicator for disease progression. MethodsA total of 263 patients with HBV infection who underwent liver biopsy in The First Affiliated Hospital of Guangxi Medical University from April 2010 to April 2024 were included， and their clinical data were collected. According to the results of pathological examination， they were divided into non-significant fibrosis group （F<2） with 126 patients and significant fibrosis group （F≥2） with 137 patients. The correlation of MDA and FIB-4 with liver fibrosis degree was analyzed， and MDA and FIB-4 were compared in terms of their accuracy in assessing significant liver fibrosis. A total of 62 patients completed follow-up， and according to the presence or absence of progression to liver cirrhosis at the last follow-up visit， they were divided into progressive group with 21 patients and non-progressive group with 41 patients； the efficacy of MDA and FIB-4 in diagnosing disease progression was analyzed and compared. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Bonferroni method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data. The Spearman’s correlation coefficient was used for correlation analysis. The Wilcoxon signed rank sum test was used for the analysis of baseline data and data at the end of follow-up， and the binary Logistic regression analysis was used to investigate the influencing factors for progression to liver cirrhosis. The receiver operating characteristic （ROC） curve was used to investigate the diagnostic efficacy of indicators， the Z-test was used for comparison of the area under the ROC curve （AUC）， and the paired chi-square test was used for comparison of the sensitivity， specificity， and accuracy of the two indicators. ResultsThe correlation coefficient between FIB-4 and liver fibrosis degree was 0.378， while the correlation coefficient between MDA and liver fibrosis degree was -0.325 （both P<0.001）. FIB-4 had an AUC of 0.688， a sensitivity of 64.96%， a specificity of 68.87%， a positive predictive value of 67.42%， a negative predictive value of 63.36%， an accuracy of 65.40%， and a cut-off value of 1.01， while MDA had an AUC of 0.653， a sensitivity of 52.55%， a specificity of 78.57%， a positive predictive value of 72.73%， a negative predictive value of 60.37%， an accuracy of 65.02%， and a cut-off value of 0.29， suggesting that compared with FIB-4， MDA had a lower sensitivity （P=0.004） and a higher specificity （P=0.001）. The progressive group had a significantly higher age than the non-progressive group at baseline （t=2.611， P=0.011）. For the progressive group， there was an increase in FIB-4 and a reduction in MDA from baseline to the end of follow-up （both P<0.001）， while the non-progressive group showed no significant changes （both P>0.05）. The multivariate Logistic regression analysis showed that aspartate aminotransferase （odds ratio ［OR］=0.940， 95% confidence interval ［CI］： 0.885‍ ‍—‍ ‍0.998， P<0.05） and MDA （OR=0.445， 95%CI： 0.279‍ ‍—‍ ‍0.710， P<0.001） were independent influencing factors for disease progression. MDA had an AUC of 0.893 and an optimal cut-off value of -0.01 in diagnosing the disease progression of liver cirrhosis. ConclusionMDA has a comparable accuracy to FIB-4 in the diagnosis of significant liver fibrosis， and MDA<-0.01 has a high accuracy in diagnosing the progression of liver fibrosis to liver cirrhosis， which can help to reduce the need for liver biopsy in clinical practice.

Objective:To investigate the influence and mechanism of bone marrow mesenchymal stem cells (BMSCs) overexpressing growth arrest specific 6, i.e. GAS6/BMSCs on full-thickness skin defect wounds in diabetic mice.Methods:This study was an experimental study. Twelve 8-week-old male C57BL/6J mice were divided into a control wound group with only full-thickness skin defects and a diabetic wound group with diabetic full-thickness skin defects according to the random number table method, with 6 mice in each group. The wound healing rates were calculated at 3, 7, 14, and 21 days after injury. At 21 days after injury, wound tissue specimens were collected for hematoxylin-eosin staining to observe the histopathological conditions; Masson staining was performed to detect collagen deposition; immunohistochemical staining was performed to detect the number of proliferating cell nuclear antigen (PCNA)-positive cells and CD31-positive cells, representing cell proliferation and capillary density, respectively; immunofluorescence staining was performed to detect the number of F4/80 and myeloperoxidase (MPO) double-positive cells, indicating efferocytosis. Two 4-week-old male C57BL/6J mice were used to extract BMSCs, and GAS6/BMSCs were constructed through adenovirus transfection and successfully identified. Eighteen 8-week-old male C57BL/6J mice were used to create diabetic full-thickness skin defect wound models and divided into phosphate buffered solution (PBS) group, BMSC group, and GAS6/BMSC group (with 6 mice in each group) according to the random number table method. Immediately after injury, PBS, BMSC single-cell suspension, and GAS6/BMSC single-cell suspension were injected locally into the wounds of the three groups of mice, respectively. The wound healing rates were calculated, and the cell proliferation, capillary density, and efferocytosis were detected at the same time points as the previous experiments.Results:At 3, 7, 14, and 21 days after injury, the wound healing rates of mice in diabetic wound group were significantly lower than those in control wound group (with t values of 7.99, 8.62, 9.80, and 5.85, respectively, P<0.05). Compared with those in control wound group, the wound tissue of mice in diabetic wound group showed the infiltration of a large number of inflammatory cells and reduced collagen deposition at 21 days after injury. At 21 days after injury, the number of PCNA-positive cells and CD31-positive cells in the wound tissue of mice in diabetic wound group were significantly less than that in control wound group (with t values of 6.61 and 5.38, respectively, P<0.05). At 21 days after injury, the number of F4/80 and MPO double-positive cells in the wound tissue of mice in diabetic wound group was 3.3±0.8, which was significantly less than 12.7±1.8 in control wound group ( t=11.00, P<0.05). At 14 and 21 days after injury, the wound healing rates of mice in BMSC group were significantly higher than those in PBS group ( P<0.05); at 3, 7, 14, and 21 days after injury, the wound healing rates of mice in GAS6/BMSC group were significantly higher than those in BMSC group ( P<0.05). At 21 days after injury, the number of PCNA-positive cells in the wound tissue of mice in BMSC group was significantly higher than that in PBS group ( P<0.05), and the number of PCNA-positive cells and CD31-positive cells in the wound tissue of mice in GAS6/BMSC group were significantly higher than that in BMSC group ( P<0.05). At 21 days after injury, the number of F4/80 and MPO double-positive cells in the wound tissue of mice in BMSC group was 4.2±1.2, which was similar to 3.5±1.1 in PBS group ( P>0.05); the number of F4/80 and MPO double-positive cells in the wound tissue of mice in GAS6/BMSC group was 8.2±1.2, which was significantly more than that in BMSC group ( P<0.05). Conclusions:Dysfunctional efferocytosis of macrophage exists in the full-thickness skin defect wounds of diabetic mice, while GAS6/BMSC can promote wound healing by restoring the efferocytosis of macrophages.

Objective:To investigate the influence and mechanism of bone marrow mesenchymal stem cells (BMSCs) overexpressing growth arrest specific 6, i.e. GAS6/BMSCs on full-thickness skin defect wounds in diabetic mice.Methods:This study was an experimental study. Twelve 8-week-old male C57BL/6J mice were divided into a control wound group with only full-thickness skin defects and a diabetic wound group with diabetic full-thickness skin defects according to the random number table method, with 6 mice in each group. The wound healing rates were calculated at 3, 7, 14, and 21 days after injury. At 21 days after injury, wound tissue specimens were collected for hematoxylin-eosin staining to observe the histopathological conditions; Masson staining was performed to detect collagen deposition; immunohistochemical staining was performed to detect the number of proliferating cell nuclear antigen (PCNA)-positive cells and CD31-positive cells, representing cell proliferation and capillary density, respectively; immunofluorescence staining was performed to detect the number of F4/80 and myeloperoxidase (MPO) double-positive cells, indicating efferocytosis. Two 4-week-old male C57BL/6J mice were used to extract BMSCs, and GAS6/BMSCs were constructed through adenovirus transfection and successfully identified. Eighteen 8-week-old male C57BL/6J mice were used to create diabetic full-thickness skin defect wound models and divided into phosphate buffered solution (PBS) group, BMSC group, and GAS6/BMSC group (with 6 mice in each group) according to the random number table method. Immediately after injury, PBS, BMSC single-cell suspension, and GAS6/BMSC single-cell suspension were injected locally into the wounds of the three groups of mice, respectively. The wound healing rates were calculated, and the cell proliferation, capillary density, and efferocytosis were detected at the same time points as the previous experiments.Results:At 3, 7, 14, and 21 days after injury, the wound healing rates of mice in diabetic wound group were significantly lower than those in control wound group (with t values of 7.99, 8.62, 9.80, and 5.85, respectively, P<0.05). Compared with those in control wound group, the wound tissue of mice in diabetic wound group showed the infiltration of a large number of inflammatory cells and reduced collagen deposition at 21 days after injury. At 21 days after injury, the number of PCNA-positive cells and CD31-positive cells in the wound tissue of mice in diabetic wound group were significantly less than that in control wound group (with t values of 6.61 and 5.38, respectively, P<0.05). At 21 days after injury, the number of F4/80 and MPO double-positive cells in the wound tissue of mice in diabetic wound group was 3.3±0.8, which was significantly less than 12.7±1.8 in control wound group ( t=11.00, P<0.05). At 14 and 21 days after injury, the wound healing rates of mice in BMSC group were significantly higher than those in PBS group ( P<0.05); at 3, 7, 14, and 21 days after injury, the wound healing rates of mice in GAS6/BMSC group were significantly higher than those in BMSC group ( P<0.05). At 21 days after injury, the number of PCNA-positive cells in the wound tissue of mice in BMSC group was significantly higher than that in PBS group ( P<0.05), and the number of PCNA-positive cells and CD31-positive cells in the wound tissue of mice in GAS6/BMSC group were significantly higher than that in BMSC group ( P<0.05). At 21 days after injury, the number of F4/80 and MPO double-positive cells in the wound tissue of mice in BMSC group was 4.2±1.2, which was similar to 3.5±1.1 in PBS group ( P>0.05); the number of F4/80 and MPO double-positive cells in the wound tissue of mice in GAS6/BMSC group was 8.2±1.2, which was significantly more than that in BMSC group ( P<0.05). Conclusions:Dysfunctional efferocytosis of macrophage exists in the full-thickness skin defect wounds of diabetic mice, while GAS6/BMSC can promote wound healing by restoring the efferocytosis of macrophages.

AIM To study the chemical constituents from n-butanol fraction of Corydalis impatiens(Pall.)Fisch.and their antioxidant activities.METHODS The n-butanol fraction was isolated and purified by silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activities were determined by DPPH method and tyrosinase method.RESULTS Fourteen compounds were isolated and identified as nicotinamide(1),methyl L-pyroglutamate(2),bungeanoline F(3),monomethyl fumarate(4),5-hydroxymethylfurfural(5),4-hydroxybenzoic acid(6),hydroxybenzoate(7),methyl 3,4-dihydroxybenzoate(8),methyl ferulate(9),dimethylcaffeic acid(10),dimethyl feruloyl malate(11),(-)-4-O-feruloylquinic acid(12),syringaresinol(13)and(-)-loliolide(14).Compounds 1,8,11 and 13 showed strong antioxidant activites on DPPH free radicals,with IC50 values ranging from 54.47 to 97.4 μmol/L.Compound 13 had potential inhibitory effect on tyrosinase.CONCLUSION Compounds 4-14 are first isolated from Corydalis genus,and 3 is isolated from this plant for the first time.Compounds 1,8,11 and 13 have strong antioxidant activities.

Objective To analyze the clinical and serological typing characteristics of invasive Haemophilus influ-enzae(Hin)infection in children.Methods Clinical data of 34 children with invasive Hin infection admitted to Children's Hospital of Shanxi from 2015 to 2021 were analyzed retrospectively.According to clinical diagnosis,they were divided into meningitis infection group and non-meningitis infection group.General data,symptoms,signs,laboratory serological indicators,and Hin serum typing characteristics of children,as well as differences in inflammatory factor level between the two groups were analyzed.Results Among the 34 patients,22 were males and 12 were females,with a male to female ratio of 1.83∶1.Children aged ≤36 months accounted for 82.35％.The levels of procalcitonin(PCT)(23.71[4.10,77.80])ng/mL and C-reactive protein(CRP)(200.00[164.55,200.00])mg/L in children in the meningitis infection group were higher than those in the non-meningitis group(1.08[0.49,6.00]ng/mL,69.46[48.09,125.63]mg/L,respectively),with statistically significant differences(both P＜0.05).The platelet(PLT)count in the non-meningitis group([312.56±186.81]× 109/L)was higher than that in the meningitis group([183.28±165.67]× 109/L),with statistically significant difference(P＜0.05).There was no statistically significant difference in white blood cell(WBC)count and neutrophil(NEUT)percentage between two groups(both P＞0.05).Among the isolated Hin strains,27,2,and 2 strains were type b(Hib),e and f,respectively;3 strains were not typed;serotype a,c and d strains were not found.There was no statistically significant difference in the distribution of typeable Hin strains between the two groups(x2=0.25,P＞0.05).There was no statistically significant difference in the constituent rate of typeable Hin strains between male and fe-male children(67.74％vs 32.26％,x2=1.42,P＞0.05).Conclusion The majority of invasive Hin infection cases are children under 3 years old,and the predominant strain is type b.CRP and PCT levels of infected children in-creased significantly,while PLT is significantly lower than that of non-infected children,which has certain clinical diagnostic value and can provide effective support for early classified diagnosis and anti-infection treatment of inva-sive infectious diseases combined with other clinical testing items.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

In the current landscape of forensic psychiatric evaluation, the use of objective assessment techniques to gauge the extent of mental disability is a relatively unexplored territory. The development and enhancement of these techniques are at the forefront of our research. Daily life ability is a crucial factor in the forensic evaluation of mental disability. Given the profound influence of prospective memory on an individual′s daily life ability, its assessment could hold significant value in this context. This article presents a comprehensive review of studies on prospective memory assessment and the underlying neurophysiological and psychological mechanisms in patients with traumatic brain injuries. Our aim is to delve deeper into the potential application of prospective memory assessment in the forensic evaluation of mental disability, a novel and promising area of research.

In the current landscape of forensic psychiatric evaluation, the use of objective assessment techniques to gauge the extent of mental disability is a relatively unexplored territory. The development and enhancement of these techniques are at the forefront of our research. Daily life ability is a crucial factor in the forensic evaluation of mental disability. Given the profound influence of prospective memory on an individual′s daily life ability, its assessment could hold significant value in this context. This article presents a comprehensive review of studies on prospective memory assessment and the underlying neurophysiological and psychological mechanisms in patients with traumatic brain injuries. Our aim is to delve deeper into the potential application of prospective memory assessment in the forensic evaluation of mental disability, a novel and promising area of research.

Humans ; Rituximab/therapeutic use* ; Bendamustine Hydrochloride/therapeutic use* ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Lymphoma, B-Cell ; Protein Kinase Inhibitors/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Treatment Outcome