Simultaneous integrated boost intensity-modulated radiotherapy post breast-conserving surgery: clinical efficacy, adverse effects, and cosmetic outcomes in breast cancer patients.

BACKGROUND: Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) is an innovative technique delivering a higher dose to the tumor bed while irradiating the entire breast. This study aims to assess the clinical outcomes, adverse effects, and cosmetic results of SIB-IMRT following breast-conserving surgery in breast cancer patients. METHODS: We conducted a retrospective analysis of 308 patients with stage 0-III breast cancer who underwent breast-conserving surgery and SIB-IMRT from January 2016 to December 2020. The prescribed doses included 1.85 Gy/27 fractions to the whole breast and 2.22 Gy/27 fractions or 2.20 Gy/27 fractions to the tumor bed. Primary endpoints included overall survival (OS), local-regional control (LRC), distant metastasis-free survival (DMFS), acute and late toxicities, and cosmetic outcomes. RESULTS: The median follow-up time was 36 months. The 3-year OS, LRC, and DMFS rates were 100%, 99.6%, and 99.2%, respectively. Five patients (1.8%) experienced local recurrence or distant metastasis, and one patient succumbed to distant metastasis. The most common acute toxicity was grade 1-2 skin reactions (91.6%). The most common late toxicity was grade 0-1 skin and subcutaneous tissue reactions (96.7%). Five patients (1.8%) developed grade 1-2 upper limb lymphedema, and three patients (1.1%) had grade 1 radiation pneumonitis. Among the 262 patients evaluated for cosmetic outcomes at least 2 years post-radiotherapy, 96.9% achieved excellent or good results, while 3.1% had fair or poor outcomes. CONCLUSIONS: SIB-IMRT after breast-conserving surgery in breast cancer patients demonstrated excellent clinical efficacy, mild acute and late toxicities, and satisfactory cosmetic outcomes in our study. SIB-IMRT appears to be a feasible and effective option for breast cancer patients suitable for breast-conserving surgery.

Effectiveness of WeChat-assisted preoperative education to reduce perioperative anxiety in breast cancer patients: a prospective randomized controlled study protocol.

BACKGROUND: Breast cancer is the most prevalent cancer among women globally, and surgical procedures continue to be the primary treatment. However, over 50% of patients experience preoperative anxiety due to the unknown and fear associated with surgery. Although drug therapy is commonly used to address this anxiety, its side effects have led to a heated debate regarding its effectiveness. Consequently, non-pharmacological therapies, such as preoperative education, have emerged as an alternative approach to alleviate anxiety. WeChat, a widely popular social media platform, offers a public platform that can potentially be utilized for effective preoperative education. This study aims to evaluate the use of WeChat public platform as a tool for preoperative education in patients undergoing breast surgery. METHODS: This is a prospective, randomized, and controlled trial will involve 392 adult women scheduled for breast cancer resection. Participants will be randomly assigned to either the WeChat education group or the regular group. In addition to regular preoperative visits, the WeChat education group will also watch science videos through the WeChat public platform. The regular group will only receive education from ward nurses during preoperative visits. The primary outcome measure will be the incidence of preoperative anxiety, defined by scores of the State Anxiety Inventory (SAI) exceeding 40 points. Secondary outcome measures include the incidence of severe anxiety (SAI > 44) on the day before surgery, incidence of anxiety 72 h after surgery, incidence of severe anxiety 72 h after surgery, NRS scores for pain at rest and during activity 24, 48, and 72 h after surgery, incidence of nausea and vomiting within 24 h after surgery, subjective sleep score at 1 week postoperatively, quality of life QoR-15 scores at 1 and 3 months postoperatively, incidence of chronic pain at 3 months postoperatively, bowel function recovery, length of hospital stay, and hospitalization expenses. DISCUSSION: This is the first clinical trial to investigate the use of WeChat public platform for delivering preoperative education on perioperative anxiety in breast cancer patients. By utilizing the renowned WeChat public platform, our study aims to improve patient outcomes by providing video education that explains the disease, surgery, and anesthesia in a more accessible manner, thereby reducing the incidence of perioperative anxiety. If our hypothesis is confirmed, this non-pharmacological approach can be universally acknowledged as a cost-effective and practical method in clinical care. Its application can also be extended to other medical fields beyond breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05291494. Registered on 29 December 2021.

Anesthetic management of a child with double outlet right ventricle and severe polycythemia: A case report.

BACKGROUND: Double outlet right ventricle (DORV) is a rare and complex congenital heart defect, and the surgical repairs vary with type and pathophysiology consequences. Due to prolonged progressive hypoxemia, severe polycythemia is common in patients with DORV, which ultimately leads to coagulation dysfunction and increases the risk of thrombosis and infarction. Consequently, the anesthetic management is challenging and how to manage severe polycythemia and avoid hypoxia-related complications in such patients is of great significance. CASE SUMMARY: Herein, we report the anesthetic management of a 10-year-old female patient with a DORV. She lived in the low-oxygen Qinghai-Tibet Plateau, and presented with severe polycythemia (hemoglobin, 24.8 g/dL; hematocrit, 75%). She underwent a modified Fontan surgery, which was satisfactory and without any perioperative complications. Our anesthetic management highlights the importance of perioperative hemodilution in decreasing the risk of thromboembolism and the importance of correcting coagulopathy in preventing hemorrhage. CONCLUSION: Anesthetic management is challenging in rare cyanotic congenital heart disease patients with severe polycythemia. It is important to adopt perioperative hemodilution and correction of coagulopathy in preventing thrombosis and hemorrhage.

Salvianolic acid B decreases interleukin-1ß-induced colitis recurrence in mice.

BACKGROUND: Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence. METHODS: Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1ß (IL-1ß) was injected intraperitoneally to induce colitis recurrence. RESULTS: Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ±â€Š3.46% to 162.89 ±â€Š11.45% (P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ±â€Š9.29% to 296.23 ±â€Š30.78% (P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ±â€Š8.45% vs. 162.89 ±â€Š11.45%, P = 0.0059) and Sal B (104.27 ±â€Š6.09% vs. 162.89 ±â€Š11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ±â€Š89.42% vs. 296.23 ±â€Š30.78%, P = 0.0028) but not influenced by SASP (285.23 ±â€Š41.04% vs. 296.23 ±â€Š30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1ß in Sal B-treated group was significantly lower than that in SASP-treated group. CONCLUSIONS: These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.

Risk factors and distribution features of level IB lymph nodes metastasis in nasopharyngeal carcinoma.

OBJECTIVE: The objective of this study is to investigate the risk factors and distribution features for level IB metastasis in nasopharyngeal carcinoma (NPC) and provide clinical evidence for defining the indications and clinical target volume (CTV) of prophylactic level IB irradiation. METHODS: We retrospectively analyzed 798 patients with newly-diagnosed, non-metastatic and histologically confirmed NPC underwent intensity-modulated radiation therapy (IMRT). Two sides of neck in each patient have been analyzed separately. The correlations of level IB metastasis and the clinical risk factors were analyzed with Chi-square test and logistic regression model. The risk score model (RSM) of level IB metastasis was calculated by totaling up the scores of each independent variable. We divided level IB into three areas, including anterolateral space of submandibular glands, medial space of the submandibular glands and submandibular glands. RESULTS: Maximal axial diameter (MAD) of level IIA nodes >20mm or extra capsular spread (ES) of level IIA nodes, anterior half of nasal cavity involvement and submandibular gland involvement/compression were independently significantly risk factors for level IB lymph nodes (LNs) metastasis at diagnosis. Two groups based on RSM were obtained: low risk (total score=0-2.5); high risk (4-8.5). The incidence of IB LNs metastasis at diagnosis of the two groups were 0.9% and 6.3%, respectively (P<0.001). The cervical lymph nodes of level IB were distributed in the anterolateral space of submandibular glands. There was no positive/negative LNs inside or medial space of the submandibular glands. CONCLUSION: Level IB LNs metastasis is associated with MAD of level IIA nodes >20mm or ES of level IIA nodes, anterior half of nasal cavity involvement and submandibular gland involvement/compression in NPC patients. Omission of level IB irradiation may be feasible for patients with low-risk IB LNs metastasis at diagnosis. The submandibular gland should not be included in level IB.

[Passive leg raising predicts volume responsiveness in patients with severe sepsis and septic shock].

OBJECTIVE: To evaluate the role of passive leg raising (PLR) test in predicting volume responsiveness in severe sepsis and septic shock patients. METHODS: Thirty severe sepsis and septic shock patients in intensive care unit (ICU) of Peking University Shenzhen Hospital were prospectively observed from February 2009 to January 2010. The hemodynamics including stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) were measured non invasively by ultrasonic cardiac output monitor (USCOM) device in the supine position, during PLR and after volume expansion (VE), and invasive arterial blood pressure and central venous pressure (CVP) were monitored consecutively. Responders were defined by the appearance of an increase in SV (ΔSV) ≥ 15% after VE. The role of PLR for predicting volume responsiveness was evaluated by receiver operating characteristic (ROC) curves. RESULTS: The CVP (cm H(2)O, 1 cm H(2)O=0.098 kPa) during PLR was increased compared with that at supine position in both responder group ( n =15) and non responder group ( n =15, 13.6 ± 6.6 vs. 12.1 ± 6.0, 11.9 ± 5.5 vs. 10.8 ± 5.2 , both P <0.01). ΔSV was higher in responder group than in non responder group during PLR [(16.6 ± 5.5)% vs. (3.8 ± 8.2)%, P=0.000].ΔSV during PLR was highly correlated to ΔSV after VE (r =0.681 , P =0.000).The area under the ROC curve (AUC) for PLR predicting volume responsiveness was 0.944 ± 0.039 ( P =0.000). The ΔSV>11% during PLR was found to predict volume responsiveness with a sensitivity of 86.7%, specificity of 93.3%, positive predictive value of 92.9% and negative predictive value of 87.5%. CONCLUSION: PLR can be used generally to predict volume responsiveness accurately in severe sepsis and septic shock patients, and it can be used to direct clinical practice.

[Effect of AT1 receptor on changes of tyrosine hydroxylase-immunoreactivity in rostral ventrolateral medulla induced by brain cholinergic stimuli in rats].

OBJECTIVE: To investigate the effect of AT1 receptor on the changes of tyrosine hydroxylase-immunoreactivity (TH-IR) in rostral ventrolateral medulla (RVLM) induced by brain cholinergic stimuli in rats. METHODS: Male SD rats were randomly divided into 4 groups: NS + CBC group, Los + CBC group, Los + NS group and NS + NS group. AT1 was blocked by pretreatment of 20 µg losartan in Los + CBC and Los + NS groups; intracerebroventricular injection of 0.5 µg carbachol was used for cholinergic stimuli in NS + CBC and Los + CBC groups; normal saline (NS) was used for control. The output amount of natrium in kidney, glomerular filtration rate (GFR) and renal plasma flow (PRF) were observed. The changes of TH-IR in the RVLM were observed by immunohistochemistry. RESULT: In NS + CBC group carbachol induced potent natriuresis, after pretreatment of losartan the natriuretic effect was partially inhibited in Los + CBC group. Both the number and optical density of TH-IR positive neurons in NS + CBC group were markedly increased than those in NS + NS group (P < 0.05); while those in Los + CBC group were significantly lower than those in NS+CBC group (P < 0.05). Intracerebroventricular injection of carbachol and losartan had no effect on GFR and RPF(P > 0.05). CONCLUSION: The results suggest that cholinergic stimuli can induce potent natriuresis and increase the activity of adrenergic neurons in the RVLM; the above effects can be down regulated by blockade of brain AT1 receptor.

[Total hepatic ischemia-reperfusion-induced lung injury in rats and protective effects of melatonin].

OBJECTIVE: To explore total hepatic ischemia-reperfusion(I/R)-induced lung injury in rats,its related mechanism and the protective effects of melatonin on lungs. METHODS: This study was divided into 2 parts. In the first part, 72 healthy male SD rats weighing 250-300 g were randomly divided into 2 groups: I/R group(ischemia-reperfusion,n=36) and sham-operation group(n=36). Total hepatic I/R was produced by occlusion of hepatic helium for 30 minutes, and the occlusion was then released for reperfusion. The animals were killed at 5 minutes prior to ischemia and 0 h, 0.5 h, 1 h, 3 h and 6 h after reperfusion in sham-operation group and I/R group (n=6 at each time point), and the lung tissue was taken. Through comparisons of these two groups, we observed the dynamic changes of lung tissue after total hepatic I/R. In the second part, 12 healthy male SD rats weighing 250-300 g were randomly divided into 2 groups: melatonin group(n=6) and vehicle group(n=6). Melatonin (0.5%,10 mg/kg)or vehicle of the same volume was injected via femoral vein 15 min before ischemia and 10 min before reperfusion, the animals were killed at 1 h after reperfusion, and the lung tissue was taken. Through comparisons of these two groups, we observed the effects of melatonin. RESULTS: (1)Total hepatic I/R led to severe histological injury in lungs. Compared with those in sham-operation group, the MDA content and apoptotic index were increased, the SOD activity was decreased, the p-ERK/ERK ratio and PCNA-positive index were decreased respectively 0 h and 0.5 h after reperfusion, and then were increased gradually. Histological examination revealed that the alveolar architecture was destroyed with interstitial thickening and neutrophil infiltration in I/R group. Correlate analysis revealed that p-ERK/ERK ratio showed a positive correlation with PCNA-positive index(r=0.56, P<0.05) and apoptotic index (r=0.62, P<0.05) in I/R group. (2)Melatonin treatment alleviated total hepatic I/R-induced lung injury. In melatonin group, the histological change was less severe compared with that in vehicle group; the MDA content and apoptotic index were lower, the SOD activity and p-ERK/ERK ratio were higher than those in vehicle group at the same time, but PCNA-positive index showed no difference. CONCLUSION: Total hepatic I/R led to severe lung injury. The aggravation of lipid peroxidation, reduced capability of scavenging free radical and aggravation of apoptosis were important factors causing hepatic I/R induced lung injury. Melatonin had protective effect on lung injury induced by total hepatic I/R, which was mediated by anti-oxidation and anti-apoptosis, but the relationship between melatonin's protective effects and activation of ERK1/2 signal transduction pathway remained to be explored.

[Survey of suicidal ideation and suicide attempts in outpatients at 50 general hospitals in Beijing].

OBJECTIVE: Describe the prevalence and risk factors for suicidal ideation and suicide attempt among outpatients at general hospitals in Beijing. METHODS: Trained psychiatric nurses obtained data about the characteristics of suicidal thoughts and suicide attempts from 2877 persons 15 years of age or older who were consecutive outpatients at 35 level-1, 8 level-2 and 7 level-3 general hospitals selected from all hospitals in Beijing by stratified random sampling. Logistic regression analysis was used to identify risk factors for suicidal ideation and suicide attempt. RESULTS: The lifetime prevalence of suicidal ideation and suicide attempt were 6.08% (95% CI: 5.25% - 7.25%) and 1.18% (0.82% - 1.65%), respectively. Mutivariate logistic analysis found that the most important risk factors for suicidal ideation were hopelessness in the prior year (OR = 7.96), current depression (OR = 3.41), younger age (OR for < 35 = 2.83; OR for 35 - 55 = 2.08), having a blood relative with prior suicidal behavior (OR = 2.58), and so forth; the most important risk factors for suicide attempt were younger age (OR for < 35 = 4.96; OR for 35 - 55 = 4.40), hopelessness in the prior year (OR = 4.02), self-report of health status in last weeks as poor (OR = 2.81), not currently married (never married, divorced, widowed, etc) (OR = 2.80), and so forth. Four variables were independent risk factors for both suicidal ideation and suicide attempt: hopelessness in the last year, younger age, having associates with prior suicidal behavior and female gender. CONCLUSIONS: Many patients treated at medical, surgical and other outpatient departments of general hospitals in Beijing are depressed and at risk for suicide; this is particularly true of young female patients who feel hopeless about their future. Outpatient clinicians need to be trained to identify such patients, to assess the severity of their psychological problems and, if necessary, to provide appropriate treatment or refer them for psychiatric evaluation.

[The role of AT1 receptor in the changes in TH immunoreactivity of LC induced by brain cholinergic stimulation].

AIM AND METHODS: In the present study, we investigated the TH immunoreactivity and the expression of angiotensin AT1 receptor in locus coeruleus after intracerebroventricular (i. c. v.) injection of carbachol in conscious SD rats with immunohistochemistry. Meanwhile the effects of blocking AT1 receptor were also observed. RESULTS: Both mean optical density and number of TH and AT1 immunoreactive positive neurons were markedly increased in locus coeruleus after 40 minutes of i.c.v. injection of carbachol (0.5 microg). The enhancement was significantly reduced by i. c. v. injection of losartan. CONCLUSION: The results above suggest that i. c. v. injection of cholinergic agonist carbachol can enhance the activity of adrenergic neurons and the expression of AT1 receptor in locus coeruleus. The blockade of AT1 receptor may down regulate the above action induced by carbachol in locus coeruleus.

[Characteristics of mental health services at 325 general hospitals in Beijing].

OBJECTIVE: Describe the mental health services provided at different types of general hospitals in Beijing. METHODS: Distribute the "Hospital Mental Health Services Survey" to all 508 hospitals in the 18 Beijing districts; the survey covers information for 2001 on the type of mental health services provided, the characteristics of the service providers, the number and diagnoses of first-visit mental health patients, and the prescription of psychotropic medications. RESULTS: 73% (373/508) of the hospitals completed the survey, including 75% (325/436) of the general hospitals. Among the 325 general hospitals, 171 (53%) provided one or more types of mental health services; they had a total of 420 staff members who provide these services, but their educational level was relatively low and mental health training limited. 61 general hospitals had mental health outpatient departments that treated 50% (47,151/93,891) of all first-visit mental health patients seen in all hospitals (including psychiatric hospitals) in the municipality; 90% (42,578/47,151) of these first-visit patients in general hospitals were seen at 18 level-3 hospitals. Among the 44,441 first-visit patients for whom diagnostic information was available, the main diagnoses were neurosis (43%) and depression (30%). 103 of the participating general hospitals prescribed 73% of antidepressant medications prescribed at all hospitals in the municipality and 97% of all fluoxetine (Prozac and others). CONCLUSIONS: General hospitals-particularly level-1 and level-2 general hospitals-need to put more emphasis on mental health services, increase training of staff who provide the services and open relevant departments. Monitoring the development of mental health services in general hospitals and increasing the quality of their mental health services will require periodic assessment of the types and range of mental health services provided and of the diagnostic accuracy and treatment standards of the staff providing these services.

MBD3L2 interacts with MBD3 and components of the NuRD complex and can oppose MBD2-MeCP1-mediated methylation silencing.

MBD2 and MBD3 are two proteins that contain methyl-CpG binding domains and have a transcriptional repression function. Both proteins are components of a large CpG-methylated DNA binding complex named MeCP1, which consists of the nucleosome remodeling and histone deacetylase complex Mi2-NuRD and MBD2. MBD3L2 (methyl-CpG-binding protein 3-like 2) is a protein with substantial homology to MBD2 and MBD3, but it lacks the methyl-CpG-binding domain. Unlike MBD3L1, which is specifically expressed in haploid male germ cells, MBD3L2 expression is more widespread. MBD3L2 interacts with MBD3 in vitro and in vivo, co-localizes with MBD3 but not MBD2, and does not localize to methyl-CpG-rich regions in the nucleus. In glutathione S-transferase pull-down assays, MBD3L2 is found associated with several known components of the Mi2-NuRD complex, including HDAC1, HDAC2, MTA1, MBD3, p66, RbAp46, and RbAp48. Gel shift experiments with nuclear extracts and a CpG-methylated DNA probe indicate that recombinant MBD3L2 can displace a form of the MeCP1 complex from methylated DNA. MBD3L2 acts as a transcriptional repressor when tethered to a GAL4-DNA binding domain. Repression by GAL4-MBD3L2 is relieved by MBD2 and vice versa, and repression by MBD2 from a methylated promoter is relieved by MBD3L2. The data are consistent with a role of MBD3L2 as a transcriptional modulator that can interchange with MBD2 as an MBD3-interacting component of the NuRD complex. Thus, MBD3L2 has the potential to recruit the MeCP1 complex away from methylated DNA and reactivate transcription.

MBD3L1 is a transcriptional repressor that interacts with methyl-CpG-binding protein 2 (MBD2) and components of the NuRD complex.

Methyl-CpG-binding domain proteins 2 and 3 (MBD2 and MBD3) are transcriptional repressors that contain methyl-CpG binding domains and are components of a CpG-methylated DNA binding complex named MeCP1. Methyl-CpG-binding protein 3-like 1 (MBD3L1) is a protein with substantial homology to MBD2 and MBD3, but it lacks the methyl-CpG binding domain. MBD3L1 interacts with MBD2 and MBD3 in vitro and in yeast two-hybrid assays. Gel shift experiments with a CpG-methylated DNA probe indicate that recombinant MBD3L1 can supershift an MBD2-methylated DNA complex. In vivo, MBD3L1 associates with and colocalizes with MBD2 but not with MBD3 and is recruited to 5-methylcytosine-rich pericentromeric heterochromatin in mouse cells. In glutathione S-transferase pull-down assays MBD3L1 is found associated with several known components of the MeCP1.NuRD complex, including HDAC1, HDAC2, MTA2, MBD2, RbAp46, and RbAp48, but MBD3 is not found in the MBD3L1-bound fraction. MBD3L1 enhances transcriptional repression of methylated DNA by MBD2. The data are consistent with a role of MBD3L1 as a methylation-dependent transcriptional repressor that may interchange with MBD3 as an MBD2-interacting component of the NuRD complex. MBD3L1 knockout mice were created and were found to be viable and fertile, indicating that MBD3L1 may not be essential or there is functional redundancy (through MBD3) in this pathway. Overall, this study reveals additional complexities in the mechanisms of transcriptional repression by the MBD family proteins.

[The role of brain AT1 receptor in renal sodium and water excretion and the change of TH-IR in hypothalamus].

AIM AND METHODS: To investigate the role of modulation by angiotensin AT1 receptor in sodium and water excretion induced by cholinergic agonist carbachol. Tyrosine hydroxylase immunoreactivity (TH-IR) in hypothalamus were also observed. RESULTS: The natriuretic and diuretic effect induced by carbachol (CBC) were partially inhibited by pretreatment of losartan, a specific blocker of angiotensin AT1 receptor (P < 0.05). Immunohistochemistry showed that both TH-IR density and number of TH-IR positive neurons were markedly increased in PaPo, Arc, Pe and AHP of hypothalamus at 40 min after carbachol administration, as compared with NS group (P < 0.05). However, in losartan pretreated group, the number and the density of TH-IR were significantly decreased in such nuclei mentioned above except PaPo. CONCLUSION: The results above suggest that brain AT1 receptor appears to be involved in mediating natriuresis induced by cholinergic stimulus. The blockade of AT1 receptor may down regulate the excitability of adrenergic neurons in Arc, Pe and AHP induced by CBC. We postulate that brain adrenergic and angiotensinergic pathway get involved in natriuresis induced by brain cholinergic stimulus together. Moreover, angiotensinergic neurons may influence the activity of adrenergic neurons in hypothalamus.

MBD3L1 and MBD3L2, two new proteins homologous to the methyl-CpG-binding proteins MBD2 and MBD3: characterization of MBD3L1 as a testis-specific transcriptional repressor.

Methylation of cytosines at CpG dinucleotides is essential for mammalian development. MeCP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of proteins that contain a methyl-CpG binding domain (MBD). Except for MBD4, these proteins are involved in gene silencing imposed by methylated DNA. We have identified a human gene that codes for a protein that is 42% identical to MBD3 and 38% identical to MBD2 but lacks the methyl-CpG binding domain. The recombinant protein does not bind to methylated DNA in vitro. The corresponding mouse Mbd3L1 gene was also cloned. The MBD3L1 gene is expressed specifically in testis. During spermatogenesis, expression of MBD3L1 is observed only in round spermatids, suggesting a role for the gene product in the postmeiotic stages of male germ cell development. The MBD3L1 protein is localized to discrete areas in the nucleus and contains an N-terminal transcriptional repression domain. This repression is independent of histone deacetylase inhibition. A homologue of MBD3L1, MBD3L2, was also identified and cloned. Expression of MBD3L2 was found in germ cell tumors and some somatic tissues. These novel proteins may function as counterparts of MBD2 and/or MBD3 in developmental stage-specific transcriptional repression.