[Detection of BCR-ABL Fusion Gene in Chronic Myeloid Leukemia by Novel Digital PCR].

OBJECTIVE: To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABLp190/210/230. METHODS: A new dPCR system for detecting BCR-ABLp190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared. RESULTS: Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal. CONCLUSIONS: This new dPCR detection system can be applied to the detection of BCR-ABLp190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.

Does previous gastrectomy history affect the surgical outcomes of laparoscopic cholecystectomy?

PURPOSE: This current study aimed to explore whether gastrectomy history influenced surgical outcomes while undergoing laparoscopic cholecystectomy (LC). METHODS: The PubMed, Embase, and Cochrane Library databases were searched for eligible studies from inception to April 29, 2023. The Newcastle-Ottawa Scale (NOS) was adopted to assess the quality of included studies. The mean differences (MDs) and 95% confidence intervals (CIs) were calculated for continuous variables, and the odds ratios (ORs) and 95% CIs were calculated for dichotomous variables. RevMan 5.4 was used for data analysis. RESULTS: Seven studies enrolling 8193 patients were eligible for the final pooling up analysis (380 patients in the previous gastrectomy group and 7813 patients in the non-gastrectomy group). The patients in the gastrectomy group were older (MD = 11.11, 95%CI = 7.80-14.41, P < 0.01) and had a higher portion of males (OR = 3.74, 95%CI = 2.92-4.79, P < 0.01) than patients in the non-gastrectomy group patients. Moreover, the gastrectomy group had longer LC operation time (MD = 34.17, 95%CI = 25.20-43.14, P < 0.01), a higher conversion rate (OR = 6.74, 95%CI = 2.17-20.26, P = 0.01), more intraoperative blood loss (OR = 1.96, 95%CI = 0.59-3.32, P < 0.01) and longer postoperative hospital stays (MD = 1.07, 95%CI = 0.38-1.76, P < 0.01) than the non-gastrectomy group. CONCLUSION: Patients with a previous gastrectomy history had longer operation time, a higher conversion rate, more intraoperative blood loss, and longer postoperative hospital stays than patients without while undergoing LC. Surgeons should pay more attention to these patients and make prudent decisions to avoid worse surgical outcomes as much as possible.

Efficacy analysis of axillary approach in the treatment of Ideberg type I and II scapular glenoid fractures: Case series.

RATIONALE: To investigate the clinical efficacy of the axillary approach in the surgical treatment of Ideberg type I and II scapular glenoid fractures. PATIENT CONCERNS AND DIAGNOSIS: Retrospective analysis of 13 cases of scapular glenoid fracture treated in the affiliated Hospital of Jining Medical College, Jiaxiang County People hospital, Zoucheng City people Hospital, Yanzhou District People Hospital, and Juancheng County people Hospital from December 2020 to January 2022. Eight males (including 1 bilateral) and 5 females, with an average age of 57.5 years (range from 33 to 75 years). According to Ideberg classification, there were 10 cases of type I a, 1 case of type I a combined with type I b, and 2 cases of type II. All patients were treated with axillary approach surgery and 7 patients with combined anterior shoulder dislocation were treated by first-stage manipulation and second-stage reoperation. Seven patients were fixed with a wire anchor, 3 patients with type I a were fixed with a "T" plate, and 5 patients were complicated with rotator cuff tear and were repaired with a wire anchor. At the last follow-up, the Constant-Murley shoulder function score, visual analog score, DASH score, and Hawkins grade were used to evaluate shoulder function, pain, and stability after treatment. INTERVENTION: The intervention was to treat patients with Ideberg type I and II scaphoid fractures using an axillary approach. OUTCOMES: All 13 patients in this group were followed up thoroughly, and the follow-up time was 12 to 25 months, with an average of 18.6 months. The operation time was 65 to 135 minutes, with an average of 85.6 minutes. Intraoperative blood loss ranged from 20 to 120 mL, averaging 55.6 mL. The duration of hospitalization ranged from 7 to 22 days, with an average of 9.6 days. The surgical incisions of all patients were grade-A healing. Bone healing of glenoid fractures was observed 3 months after the operation. LESSONS: The axillary approach for Ideberg type I and II scapular glenoid fractures is a feasible surgical approach with complete access through the muscle gap, minimal surgical trauma, mild postoperative pain, and satisfactory clinical results.

Assessment of iris volume in glaucoma patients with type 2 diabetes mellitus by AS-OCT.

AIM: To examine the change of iris volume measured by CASIA2 anterior segment optical coherence tomography (AS-OCT) in glaucoma patients with or without type 2 diabetes mellitus (T2DM) and explore if there is a correlation between hemoglobin A1c (HbA1c) level and iris volume. METHODS: In a cross-sectional study, 72 patients (115 eyes) were divided into two groups: primary open angle glaucoma (POAG) group (55 eyes) and primary angle-closure glaucoma (PACG) group (60 eyes). Patients in each group were separately classified into patients with or without T2DM. Iris volume and glycosylated HbA1c level were measured and analyzed. RESULTS: In the PACG group, diabetic patients' iris volume was significantly lower than those of non-diabetics (P=0.02), and there was a significant correlation between iris volume and HbA1c level in the PACG group (r=-0.26, P=0.04). However, diabetic POAG patients' iris volume was noticeably higher than those of non-diabetics (P=0.01), and there was a significant correlation between HbA1c level and iris volume (r=0.32, P=0.02). CONCLUSION: Diabetes mellitus impact iris volume size, as seen by increased iris volume in the POAG group and decreased iris volume in the PACG group. In addition, iris volume is significantly correlated with HbA1c level in glaucoma patients. These findings imply that T2DM may compromise iris ultrastructure in glaucoma patients.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Detection of BCR-ABL Fusion Gene in Chronic Myeloid Leukemia by Novel Digital PCR / 中国实验血液学杂志

OBJECTIVE@#To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABLp190/210/230.@*METHODS@#A new dPCR system for detecting BCR-ABLp190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared.@*RESULTS@#Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal.@*CONCLUSIONS@#This new dPCR detection system can be applied to the detection of BCR-ABLp190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.

The Singapore Asymptomatic Narrow Angles Laser Iridotomy Study: Five-Year Results of a Randomized Controlled Trial.

PURPOSE: To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS). DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: This multicenter, randomized controlled trial (ClinicalTrials.gov identifier, NCT00347178) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy). METHODS: Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years. MAIN OUTCOME MEASURES: The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure [IOP] of >21 mmHg, or both or acute angle closure [AAC]) or primary angle-closure glaucoma (PACG) over 5 years. RESULTS: Of the 480 randomized participants, most were Chinese (92.7%) and were women (75.8%) with mean age of 62.8 ± 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n = 24 [5.0%]; incidence rate [IR], 11.65 per 1000 eye-years) compared with control eyes (n = 45 [9.4%]; IR, 21.84 per 1000 eye-years; P = 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95% confidence interval [CI], 0.37-0.83; P = 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95% CI, 1.03-1.10; P < 0.001) and eyes with higher baseline IOP (per millimeter of mercury; HR, 1.35; 95% CI, 1.22-1.50; P < 0.0001) were more likely to reach an end point. The number needed to treat to prevent an end point was 22 (95% CI, 12.8-57.5). CONCLUSIONS: In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low.

Does PD-1 blockade play a decisive role in the pathological complete remission of unresectable MSS, BRAF V600E-mutated metastatic colorectal cancer: A case report.

Background: Colorectal cancer (CRC) ranks third in highest incidence among human cancers. With the continuous development of anti-cancer drugs, CRC patients are treated more and more effectively. However, the treatment of patients with unresectable metastatic CRC (mCRC) remains a core point for surgeons worldwide, especially for those with microsatellite stability (MSS) and BRAF V600E mutation, who have been reported to have the worst prognosis. Case description: We report a case of pathological complete remission in a patient with unresectable MSS, BRAF V600E-mutated metastatic rectal cancer after using Vemurafenib and Cetuximab in combination with Camrelizumab. Conclusions: This case suggested that Vemurafenib and Cetuximab combined with Camrelizumab is effective in the treatment of MSS, BRAF V600E-mutated mCRC. To benefit more patients, further studies need to be completed.

Chemical genetics technology regulates the activity of GLP-1 neurons and its effect on appetite / 中华内分泌代谢杂志

Objective:To conduct a glucagon like peptide-1(GLP-1)controllability model rat by chemical genetics, and observe the impact of GLP-1 neuron excitability on appetite.Methods:Fifteen rats were evenly divided into Green fluorescent protein(GFP)group, HM3D group, and HM4D group. Various combinations of adeno-associated virus(rAAV)were injected into the nucleus tractus solitarius(NTS). rAAV-GLP-1-cre and rAAV-GFP-dio were administered in rats of GFP group. The rats of HM3D group were injected with rAAV-GLP-1-cre and rAAV-HM3D-mCherry-dio while rAAV-GLP-1-cre and rAAV-HM4D-mCherry-dio were injected in rats of HM4D group . The optimal dose of clozapine N-oxide(CNO)was selected based on feeding behavior and body weight changes of rats after intraperitoneal injection of different doses of CNO. The controllability of GLP-1 neurons was confirmed by comparing with intraperitoneal injection of saline. The number of activated GLP-1 neurons in the NTS area and the expression of POMC neurons in the hypothalamus were detected 30 minutes after CNO injection.Results:GLP-1 neurons in the NTS area of rats were successfully labeled. The rat of HM3D group revealed a decrease in food intake( P=0.021)while the rat of HM4D group showed an increase( P=0.002), when given 1 mg/kg of CNO, no changes at the dose of 0.5 mg/kg and 3.0 mg/kg. Immunofluorescence showed that the activity of GLP-1 neurons in NTS of GFP group was lower than that of HM3D group( P=0.022), and higher compared with that of the HM4D group( P=0.049). The expression of GLP-1 neurons in NTS and POMC neurons in the hypothalamus of the HM3D group after intraperitoneal injection of CNO was also higher than that in the HM4D group( P=0.003). Conclusion:Using chemical genetics technology, GLP-1 controllability model rat could be successfully established via injecting varying combinations of rAAV into the NTS area of rat. Injection of 1 mg/kg CNO can effectively activate or inhibit the neuron to regulate appetite.

Effect of Zuogui pill on cognitive function in sleep-deprived rats / 中华麻醉学杂志

Objective:To evaluate the effect of Zuogui pill on cognitive function in sleep-deprived rats.Methods:Thirty SPF Sprague-Dawley male rats, aged 8 weeks, weighing about 200 g, were divided into 5 groups ( n=6 each) using a random number table method: control group (group C), sleep deprivation group (group SD), low-dose Zuogui pill group (group L), medium-dose Zuogui pill group (group M) and high-dose Zuogui pill group (group H). The model of sleep deprivation was developed by the multi-platform water environment method.In L, M and H groups, the doses of Zuogui pill were 2.42, 4.84 and 9.68 g/kg, respectively, Zuogui pill was administered by intragastric gavage at 10: 00 am every day, and the volume of fluid for intragastric gavage was 4 ml each time.In C and SD groups, pure water was used for intragastric gavage.In L, M and H groups, the liquid was prepared according to the corresponding doses of Zuogui pill for intragastric gavage, once a day for 7 consecutive days.The cognitive function was evaluated by the Morris water maze test.After the end of the second behavioral testing, blood samples from the eyeballs were collected, and then the rats were sacrificed by decapitation, and brains were removed and the hippocampus was obtained for determination of the concentrations of serum interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) and contents of malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in hippocampal tissues (by enzyme-linked immunosorbent assay) and the expression of IL-1β, IL-6 and TNF-α in hippocampal tissues (by Western blot). Results:Compared with group C, the total swimming distance and escape latency were significantly prolonged, the time of staying at the original quadrant and the number of crossing the platform were decreased, the levels of serum IL-1β, IL-6 and TNF-α in serum and hippocampal tissues were increased, the content of MDA was increased, and the contents of GSH-Px and SOD were decreased in the other groups ( P<0.05). Compared with group SD, the total swimming distance and escape latency were significantly shortened, and the time of staying at the original quadrant was prolonged, and the number of crossing the platform was increased, the levels of serum IL-1β, IL-6 and TNF-α in serum and hippocampal tissues were decreased, the content of MDA was decreased, and the contents of GSH-Px and SOD were increased in L, M and H groups ( P<0.05). Conclusions:Zuogui pill can improve the cognitive function in sleep-deprived in rats, and the mechanism is related to inhibition of inflammatory responses and improvement in the antioxidant capacity.

Analysis of Mono-ADP-Ribosylation Levels in Human Colorectal Cancer.

BACKGROUND: Colorectal cancer remains a major public health problem with high morbidity and mortality rates. In the search for the mechanisms of colorectal cancer occurrence and development, increasing attention has been focused on epigenetics. The overall level of Mono-ADP-ribosylation, an epigenetic, has not been investigated now. The aim of our study was to analysis of the overall level of mono-ADP-ribosylation in colorectal cancer. METHODS: Immunohistochemistry was used to investigate the level of mono-ADP-ribosylation in colorectal cancer and normal colorectal adjacent tissue from 64 CRC patients. The data of patient demographic, clinical and pathological characteristics were acquired and analyzed. RESULTS: Mono-ADP-ribosylation was present in both colorectal adenocarcinoma and normal colorectal tissue. The overall level of mono-ADP-ribosylation in colorectal cancer was significantly higher than that in normal colorectal adjacent tissue. In the nucleus, the majority of samples in the high-level group were colorectal adenocarcinoma (55/64), but the opposite was true for normal colorectal tissues (7/32). In particular, increases in the level of mono-ADP-ribosylation in the cytoplasm of colorectal cancer cells was associated with a greater invasion depth of the tumor. CONCLUSION: The increased level of mono-ADP-ribosylation in colorectal cancer enhances tumor invasion, which suggests that mono-ADP-ribosylation is involved in the development of colorectal cancer and may become a new direction to solve the problem of colorectal cancer.

Correlationship between ATP binding cassette subfamily B member 1 2677G>T/A gene polymorphism and cyclosporine blood concentration in patients with autoimmune diseases / 中华风湿病学杂志

Objective:To investigate the distribution of blood concentration of cyclosporine (CsA) in patients with autoimmune disease in China, and analyze the effect of genetic polymorphisms of CsA-metabolizing enzymes, transporters and target enzymes on CsA levels.Methods:Steady-state trough blood concentrations (CsA C 0) of 193 patients' were detected by enzyme multiplied immunoassay technique. The genotype of the following sites in the included patients were sequenced by reverse transcription-polymerase chain reaction (RT-PCR): cytochrome P450 (CYP) 3A420230C>T, CYP3A56986A>G, ATP binding cassette subfamily B member 1 (ABCB1)1236C>T, ABCB12677G>T/A, ABCB13435C>T, cytochrome P450 oxidoreductase (POR) 1508 C>T and formyl peptide receptor 1 (FPR1) C>G were sequenced by RT-PCR. The influence of the gene polymorphism of the above-mentioned sites on the blood concentration of CsA was analyzed by using One-way analysis of variance (ANOVA), LSD- t test, Chi-square test. Results:One hundred and ninety-three patients included took CsA. The doses ranged from 75-200 mg/d and the patients' blood concentration distribution span was wide (33.0-313.8 ng/ml). The daily dose ( χ2=21.908, P=0.001) and age( F=4.262, P=0.006) had significant effect on the plasma concentration of CsA. ABCB12677G>T/A (rs2032582) gene polymorphism impacted on the unit dose of CsA C 0 (CsA C 0/d), CsA C 0/d [(0.81±0.42) ng·ml -1·mg -1] in wild type (GG) was higher than heterozygous mutant [GT/GA, (0.65±0.30) ng·ml -1·mg -1, P=0.023) and homozygous mutant (TT/AA/TA, (0.66±0.34) ng·ml -1·mg -1, P=0.039). Conclusion:The blood concentration of patients varies greatly among individuals. The Cold of CsA in wild type patients with ABCB12677G>T/A gene is signifficantly higher than that in mutant patients.

Senescent mesenchymal stem/stromal cells and restoring their cellular functions.

Mesenchymal stem/stromal cells (MSCs) have various properties that make them promising candidates for stem cell-based therapies in clinical settings. These include self-renewal, multilineage differentiation, and immunoregulation. However, recent studies have confirmed that aging is a vital factor that limits their function and therapeutic properties as standardized clinical products. Understanding the features of senescence and exploration of cell rejuvenation methods are necessary to develop effective strategies that can overcome the shortage and instability of MSCs. This review will summarize the current knowledge on characteristics and functional changes of aged MSCs. Additionally, it will highlight cell rejuvenation strategies such as molecular regulation, non-coding RNA modifications, and microenvironment controls that may enhance the therapeutic potential of MSCs in clinical settings.

Transcriptome sequencing analysis of mono­ADP­ribosylation in colorectal cancer cells.

Colorectal cancer (CRC) is a global health concern. The role of epigenetics in tumors has garnered increasing interest. ADP ribosylation is an epigenetic modification that is associated with a variety of biological functions and diseases, and its association with tumor development and progression has been hypothesized. However, due to the limitations of available techniques and methods, ADP ribosylation of specific sites is difficult to determine. In previous studies, it was shown that arginine­117 of histone 3 (H3R117) in Lovo cells can be modified by mono­ADP­ribosylation. This site was mutated and Lovo cells overexpressing this mutant construct were established. In the present study, the expression of differentially expressed genes (DEGs) between untransfected Lovo cells and H3R117A Lovo cells was analyzed. A total of 58,174 DEGs were identified, of which 2,324 were significantly differentially expressed (q­value <0.05; fold change >2). Functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment was used to analyze the functions and possible roles of the DEGs. The DEGs were enriched in pathways associated with metabolic process, catalytic activity, organelle and chromatin structure, and dynamics. Through this comprehensive and systematic analysis, the role of mono­ADP­ribosylation in CRC was examined, providing a foundation for future studies.

First-in-Human, Healthy Volunteers Integrated Protocol of ETC-206, an Oral Mnk 1/2 Kinase Inhibitor Oncology Drug.

In the last decade, drug development has tackled substantial challenges to improve efficiency and facilitate access to innovative medicines. Integrated clinical protocols and the investigation of targeted oncology drugs in healthy volunteers (HVs) have emerged as modalities with an increase in scope and complexity of early clinical studies and first-in-human (FIH) studies in particular. However, limited work has been done to explore the impact of these two modalities, alone or in combination, on the scientific value and on the implementation of such articulated studies. We conducted an FIH study in HVs with an oncology targeted drug, an Mnk 1/2 small molecule inhibitor. In this article, we describe results, advantages, and limitations of an integrated clinical protocol with an oncology drug. We further discuss and indicate points to consider when designing and conducting similar scientifically and operationally demanding FIH studies.

Inhibition of BAG-1 induced SH-SY5Y cell apoptosis without affecting Hsp70 expression.

OBJECTIVE: To further explore the role of BCL-2 associated anthanogen-1 (BAG-1) in neuronal apoptosis and whether the effect of BAG-1 depends on heat shock protein 70 (HSP70). METHODS: RNA interference (RNAi) technology was used to inhibit the expression of BAG-1 in SH-SY5Y cells. Hypoxia-reoxygenation injury model in the SH-SY5Y cells was established. Cell Counting Kit-8 (CCK-8) was performed for cell viability. Annexin V-APC/7-AAD double-staining followed by flow cytometry was used to measure cell apoptosis. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were used to detect the messenger RNA (mRNA) and protein expression of genes, respectively. RESULTS: BAG-1 gene silencing decreased SH-SY5Y cell viability and promoted SH-SY5Y cell apoptosis after hypoxia-reoxygenation. However, the down-regulation of BAG-1 had no effect on the mRNA and protein expression of HSP70. CONCLUSION: BAG-1 could protect SH-SY5Y cells from the hypoxia-reoxygenation injury without affecting HSP70 expression.

Determination of hydroxychloroquine and its metabolites in the breast milk of patients with autoimmune disease / 中华风湿病学杂志

Objective:To determine the concentration of hydroxychloroquine (HCQ) and its active metabolite deethylhydroxychloroquine (DHCQ) in breast milk of lactating patients with autoimmune disease. To observe the safety of hydroxychloroquine in lactation period, and to explore the factors that may affect HCQ and DHCQ concentration in the milk.Methods:Lactating patients with autoimmune disease who have taken HCQ for at least 6 months were included in our study. A new high performance liquid chromatography (HPLC) method was established to detect HCQ and DHCQ levels in breast milk. Milk samples were collected at different time points: before taking the drug (0 hours), and 2 hours, 4 hours, 6 hours after taking the drug. In addition, the genotype of cytochrome CYP3A4*1G, CYP3A5*3 and CYP2D6*10 which were related to HCQ metabolism were tested by dideoxy chain termination method. Visual acuity, hearing and growth status of the patients' infants were followed up on a regular basis. T-test, one-way ANOVA and Pearson's test were used for data analysis. Results:In 15 patients, the average concentration of HCQ and DHCQ in the milk of patients taking 200 mg/d were (520±261) ng/ml and (177±112) ng/ml, respectively. While the average concentration of HCQ and DHCQ in the milk of patients taking 400 mg/d were (1 036±374) ng/ml and (397±271) ng/ml, respectively. The peak of HCQ level for 11 patients was at 4 hour after taking the drug, while the others' were at 2 hour. The breast-fed infants did not show any abnormal symptoms of hearing, vision and growth. However, cytochrome gene polymorphism did not affect the peak of HCQ and DHCQ.Conclusion:The concentration of HCQ and DHCQ in breast milk is positively correlated to the dosage. The peak level of HCQ milk is 4 hours after taking the drug. The levels of HCQ and DHCQ at 6 hours are similar as those in the whole blood. It is suggested that patients who take HCQ can feed 4 hours after taking the drug to reduce the HCQ and its active metabolites being absorbed by infants. However, the impact of HCQ on infant safety and gene polymorphism of CYP on milk concentration among individuals needs to be further verified in large sample studies and long-term follow-up.

The effect of electroacupuncture on synaptic plasticity and autophagy in a rat model of Alzheimer′s disease / 中华物理医学与康复杂志

Objective:To investigate the effect of electroacupuncture (EA) on synaptic plasticity and the expression of autophagy-related proteins in the hippocampus in Alzheimer′s disease (AD). To explore how EA might improve cognition in AD.Methods:Healthy male Sprague-Dawley rats were randomly divided into a sham operation group, a model group and an EA group. The rat model of AD was established by injecting Aβ1-42 into the bilateral CA1 area of the hippocampus. The sham operation group was injected with an equal amount of normal saline at the same site. Starting the day after the successful modelling, the EA group received 20 minutes of EA treatment at the Baihui (DU20) and bilateral Shenshu (BL23) acupoints once a day, 6 times a week for 2 weeks. The rats′ learning and memory were then tested using a Morris water maze. The long-term potentiation (LEP) in the hippocampus was assessed using a MED64 microelectrode array and any ultrastructural changes of autophagosomes were detected using an electron microscope. The expression of the autophagy-related proteins Beclin-1 and microtubule associated protein light chain 3 (LC3) in the hippocampus were determined using western blotting.Results:The escape latency was significantly shorter and the times crossing the platform increased significantly in the EA group compared with the model group. The average amplitude of the postsynaptic excitatory field potentials in the EA group was significantly higher than among the model group. There were many autophagosomes in the hippocampal neurons of the model group, significantly more than in the EA group. The LC3II/LC3I ratio and Beclin-1 protein expression decreased significantly in the EA group compared to the model group.Conclusions:EA can improve learning and memory and restore LEP in the hippocampus of rats modeling AD. The mechanism may be related to its regulation of autophagy in hippocampal neurons.

The therapeutic effect of extracorporeal shock wave therapy on patients with severe breast cancer-associated lymphedema / 中华物理医学与康复杂志

Objective:To observe any effect of extracorporeal shock wave therapy (ESWT) on patients with moderate to severe breast cancer-associated lymphedema (BCAL) with skin fibrosis and upper limb symptoms receiving complex decongestive therapy (CDT).Methods:Forty patients with moderate to severe breast cancer-associated lymphedema were randomly divided into an ESWT+ CDT group and a CDT group, each of 20. Both groups received manual lymph drainage, 5 times per week for 4 weeks with short elastic bandages or compression cuffs. The ESWT+ CDT group was additionally provided ESWT (2.0 bar, 5 Hz, 2500 pulses) twice a week for 4 weeks. Limb swelling, skin fibrosis and symptoms of lymphedema were assessed using the circumference measurement method, modified Rodnan skin scores (mRSSs), and the Breast Cancer and Lymphedema Symptoms Experience Index (BCLE-SEI) before the treatment and after 2 and 4 weeks.Results:After 2 weeks the limb volume, skin sclerosis and lymphedema symptoms of both groups had improved significantly, with the average limb volume, mRSS score and BCLE-SEI score of the ESWT+ CDT group significantly better than those of the CDT group. After 4 weeks of treatment, the limb volume, skin sclerosis and lymphedema symptoms further improved in both groups with the ESWT+ CDT group again showing significantly greater improvement.Conclusion:ESWT can further accelerate the recovery of patients with lymphatic edema after breast cancer surgery receiving CDT therapy, correct the cycle of skin fibrosis and lymphedema, and relieve complications such as limb pain. It is worthy of clinical promotion and application.

Distribution of Traditional Chinese Medicine Syndromes and Relevant Factors in 6 Months After Percutaneous Coronary Intervention / 中国实验方剂学杂志

Objective:To investigate the distribution of traditional Chinese medicine (TCM) syndromes in patients with coronary heart disease (CHD) in 6 months after interventional therapy, and to analyze relevant influencing factors. Method:The clinical data of 1 000 patients with coronary heart disease in 6 months after interventional therapy, including the four diagnosis information of TCM, were collected, and the distribution of TCM syndromes and the influencing factors were analyzed. Result:Among 48 kinds of information about the four diagnostic methods of TCM, chest pain was the most frequent (98.10%)， among 9 kinds of common TCM syndrome types, blood stasis was the most frequent (89.90%), and the others were heart-Qi deficiency syndrome, phlegm turbidity syndrome, cold-dampness syndrome, kidney-Qi deficiency syndrome, heart-Yin deficiency syndrome, kidney-Yin deficiency syndrome, Heart-Yang deficiency syndrome and kidney-Yang deficiency syndrome in turn. Among 6 common TCM syndrome types, Qi deficiency and blood stasis syndrome were the most frequent (35.40%), and the others were phlegm turbidity and blood stasis syndrome, cold congealing heart pulse syndrome, Qi-Yin deficiency syndrome, heart-kidney Yin deficiency syndrome and heart-kidney-Yang deficiency syndrome in turn. There was no significant difference in sex ratio among different syndrome types . Patients with heart-kidney Yang deficiency syndrome had no significant difference. Compared with the average age of other syndromes, there were significant differences. Common complications included hypertension, diabetes, cerebrovascular diseases and dyslipidemia, among which hypertension had the highest frequency, with significant differences from other diseases (P<0.05). Phlegm, turbidity and blood stasis were found in patients with hypertension. The risk of syndromes was higher (OR=3.29, 95% CI [2.11, 5.05]), while the risk of cold congealing heart pulse syndrome was lower (OR=0.56, 95% CI [0.32, 0.98]), the risk of Qi and Yin deficiency was higher (OR=2.88, 95% CI [2.01, 4.99]), whereas the risk of heart and kidney Yang deficiency was lower (OR=0.54, 95% CI [0.29, 0.95]) when complicated with cerebrovascular diseases. The risk of Qi deficiency and blood stasis was higher (OR=2.97, 95% CI [2.05, 5.28]), while the risk of heart and kidney Yang deficiency was lower (OR=0.54, 95% CI [0.29, 0.95])， the risk of phlegm turbidity and blood stasis was higher when complicated with dyslipidemia (OR=3.55, 95% CI [2.32, 5.29]), and the risk of heart and kidney Yang deficiency was lower (OR=0.54, 95% CI [0.29, 0.95]). The time distribution of the disease had obvious seasonal characteristics. Conclusion:The main distribution characteristics of TCM syndromes in 6 months after coronary heart disease intervention are basically the same as those in patients without intervention. The main TCM syndromes are Qi deficiency and blood stasis syndrome, phlegm turbidity and blood stasis syndrome, cold congealing heart pulse syndrome, Qi-Yin deficiency syndrome, heart-kidney Yin deficiency syndrome and heart-kidney-Yang deficiency syndrome. The distribution pattern may be related to age, complications and seasons.