The key point of transsphenoidal surgery for infradiaphragmatic craniopharyngioma：Better sellar diaphragm resection.

Background: Craniopharyngiomas have a high recurrence rate and a poor prognosis, and the key methods for reducing recurrences are unknown. The aim of this study was to explore the key points of microscopic or endoscopic transsphenoidal surgery used to treat infradiaphragmatic craniopharyngiomas. Methods: We reviewed the medical records of patients with infradiaphragmatic craniopharyngiomas who were admitted to Peking Union Medical College Hospital between 2011 and 2018. Results: When considering tumor location, all 34 patients had intrasellar tumors, with 19 of them exhibiting suprasellar extensions. Of the 34 patients, 24 patients underwent resection under the microscope and the remaining 10 patients underwent transsphenoidal endoscopic surgery. Gross total tumor resection was achieved in 16 patients. Twelve patients underwent invaded sellar diaphragm resection, while the remaining 22 patients were not. Cerebrospinal fluid leaks occurred during surgery in 18 patients. Visual acuity improved in two patients. After an average follow-up of 31.1 months, 13 patients experienced tumor recurrence. The short term recurrence rate in the sellar diaphragm resection group was significantly lower compared to the non-resected group (P < 0.001). Moreover, based on distinct surgical methods, the endoscope group displayed a reduced short term recurrence rate compared to the microscope group (P = 0.0048). Conclusion: Invaded sellar diaphragm resection emerges as a pivotal maneuver in craniopharyngioma surgery, substantively influencing tumor recurrence. Capitalizing on the advantageous angled lens of endoscopes, surgeons can achieve heightened visualization. Significantly, the endoscopic approach exhibits a superior capacity to curtail recurrence, while effectively managing potential complications, when contrasted with the microscope group.

CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.

Recently, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor-modified T cells (CAR-Ts) have been shown to have high therapeutic efficacy in hematological tumors. CD87 is highly expressed in solid tumors with an oncogenic function. To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas (iNFPAs), we first examined CD87 expression and its effects on the metabolism of iNFPA cells. We generated CD87-specific BiTE and CAR/IL-12 T cells, and their cytotoxic effects on iNFPAs cells and in mouse models were determined. CD87 had high expression in iNFPA tissue and cell samples but was undetected in noncancerous brain samples. CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects, decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice. Overall, the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.

Research on the relation between hydro-chemical and geological characteristics in karst area: Case study in Zhong Liang Mountain, Southwest China.

Karst groundwater, which is one of most important drinking water sources, is vulnerable to be polluted as its closed hydraulic relation with surface water. Thus, it is very important to identify the groundwater source to control groundwater pollution. The Pearson correlation coefficient among major ions (Na + K+, Ca2+, Mg2+, HCO3 -, SO4 2-, and Cl-) was employed to deduce the groundwater types in Zhong Liang Mountain, Southwest China. Then, the combined method of principal component analysis and cluster analysis were employed to identify the groundwater sources in a typical karst region of southwest China. The results shown that (1) the high positive correlation between cations and anions indicated the water-rock reaction of Ca-HCO3, Ca-SO4, (Na + K)-Cl, and Mg-SO4. (2) The major two principal components that would represent water-rock reaction of CaSO4 and Ca-HCO3 would, respectively, explain 60.41% and 31.80% of groundwater information. (3) Based on the two principal components, 33 groundwater samples were clustered into eight groups through hierarchical clustering, each group has similar water-rock reaction. The findings would be employed to forecast the surge water, that was an important work for tunnel construction and operation. PRACTITIONER POINTS: The components of groundwater was highly correlated with water-rock reaction. The principal component analysis screens the types of groundwater. The cluster analysis identifies the groundwater sources.

Blood Glucose Levels Moderate the Associations Between IGF-1 Levels and Choroidal Metrics in Patients With Diabetes With Acromegaly Without Diabetic Retinopathy.

Purpose: To examine the effects of serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) on choroidal structures with different blood glucose levels in patients with diabetes mellitus (DM) with acromegaly without diabetic retinopathy. Methods: Eighty-eight eyes of 44 patients with acromegaly were divided into a nondiabetic group (23 patients, 46 eyes) and a diabetic group (21 patients, 42 eyes). Forty-four age- and sex-matched healthy controls and 21 patients with type 2 DM without diabetic retinopathy were also included. Linear regression models with a simple slope analysis were used to identify the correlation and interaction between endocrine parameters and choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascular index (CVI). Results: Our study revealed significant increases in the ChT, LA, SA, and TCA in patients with acromegaly compared with healthy controls, with no difference in the CVI. Comparatively, patients with DM with acromegaly had greater ChT than matched patients with type 2 DM, with no significant differences in other choroidal parameters. The enhancement of SA, LA and TCA caused by an acromegalic status disappeared in patients with diabetic status, whereas ChT and CVI were not affected by the interaction. In the diabetic acromegaly, higher IGF-1 (P = 0.006) and GH levels (P = 0.049), longer DM duration (P = 0.007), lower blood glucose (P = 0.001), and the interaction between GH and blood glucose were associated independently with thicker ChT. Higher GH levels (P = 0.016, 0.004 and 0.007), longer DM duration (P = 0.022, 0.013 and 0.013), lower blood glucose (P = 0.034, 0.011 and 0.01), and the interaction of IGF-1 and blood glucose were associated independently with larger SA, LA, and TCA. As blood glucose levels increased, the positive correlation between serum GH level and ChT diminished, and became insignificant when blood glucose was more than 7.35 mM/L. The associations between serum IGF-1 levels and LA, SA, and TCA became increasingly negative, with LA, becoming significantly and negatively associated to the GH levels only when blood glucose levels were more than 8.59 mM/L. Conclusions: Acromegaly-related choroidal enhancements diminish in the presence of DM. In diabetic acromegaly, blood glucose levels are linked negatively with changes in choroidal metrics and their association with GH and IGF-1. Translational Relevance: We revealed the potential beneficial impacts of IGF-1 and GH on structural measures of the choroid in patients with DM at relatively well-controlled blood glucose level, which could provide a potential treatment target for diabetic retinopathy.

Deep transcranial magnetic stimulation for schizophrenia: a systematic review.

Background: The efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an intervention for schizophrenia remain unclear. This systematic review examined the efficacy and safety of dTMS for schizophrenia. Methods: A systematic search of Chinese (WanFang and Chinese Journal Net) and English databases (PubMed, EMBASE, PsycINFO, and Cochrane Library) were conducted. Results: Three randomized clinical trials (RCTs) comprising 80 patients were included in the analyses. Active dTMS was comparable to the sham treatment in improving total psychopathology, positive symptoms, negative symptoms, and auditory hallucinations measured by the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Auditory Hallucinations Rating Scale (AHRS), respectively. Only one RCT reported the effects on neurocognitive function measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB), suggesting that dTMS may only improve one Stockings of Cambridge measure (i.e., subsequent times for five move problems). All three studies reported overall discontinuation rates, which ranged from 16.7% to 44.4%. Adverse events were reported in only one RCT, the most common being tingling/twitching (30.0%, 3/10), head/facial discomfort (30.0%, 3/10), and back pain (20.0%, 2/10). Conclusion: This systematic review suggests that dTMS does not reduce psychotic symptoms in schizophrenia, but it shows potential for improving executive functions. Future RCTs with larger sample sizes focusing on the effects of dTMS on psychotic symptoms and neurocognitive function in schizophrenia are warranted to further explore these findings.

Narrative Review and Consensus Recommendations for the Use of Transnasal Humidified Rapid-Insufflation Ventilatory Exchange in Modified Electroconvulsive Therapy.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) is a safe, effective, and novel technique that is currently being used in electroconvulsive therapy (ECT). This study aimed to summarize the clinical practices of THRIVE use in ECT to aid physicians and institutions in implementing the best practice guidelines for ECT. Thus, we reviewed the current literature and presented our consensus on the application of THRIVE in ECT in daily clinical practice. This consensus provides information regarding THRIVE use in ECT, including its safety, effectiveness, procedures, precautions, special case management, and application in special populations. Moreover, it guides the standardized use of THRIVE in ECT.

Sex Differences in the Antidepressant and Neurocognitive Effects of Nonconvulsive Electrotherapy in Patients with Treatment-Refractory Depression.

Objective: The objective of this study was to examine sex differences in the antidepressant and neurocognitive effects of adjunctive nonconvulsive electrotherapy (NET) in patients with treatment-refractory depression (TRD), which has not yet been thoroughly investigated. Methods: The study enrolled 20 patients with TRD, comprising 11 males and 9 females, who underwent a series of 6 NET sessions. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess depressive symptoms, response, and remission at baseline and after the first, third, and sixth NET sessions. The Wisconsin Card Sorting Test (WCST) was used to assess neurocognitive function at baseline and after the sixth NET session. Results: After completing 6 NET sessions, female patients experiencing TRD exhibited a higher inclination toward achieving an antidepressant response (77.8% vs. 45.5%, P = .197) and antidepressant remission (22.2% vs. 0%, P = .189) when compared to their male counterparts. No significant differences were observed in changes in the HAMD-17 and WCST subscale scores (all P > .05), including completing classification number, total error number, persistent error number, and random error number between males and females. Additionally, no significant correlations were observed between baseline WCST subscale scores and changes in HAMD-17 scores or endpoint scores, irrespective of sex (all P > .05). Conclusion: These pilot findings suggest that female patients with TRD exhibited increased rates of achieving antidepressant response and remission after undergoing NET. However, further studies should be conducted to confirm these findings.

Artificial neural network identified a 20-gene panel in predicting immunotherapy response and survival benefits after anti-PD1/PD-L1 treatment in glioblastoma patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a promising immunotherapy approach, but glioblastoma clinical trials have not yielded satisfactory results. OBJECTIVE: To screen glioblastoma patients who may benefit from immunotherapy. METHODS: Eighty-one patients receiving anti-PD1/PD-L1 treatment from a large-scale clinical trial and 364 patients without immunotherapy from The Cancer Genome Atlas (TCGA) were included. Patients in the ICI-treated cohort were divided into responders and nonresponders according to overall survival (OS), and the most critical responder-relevant features were screened using random forest (RF). We constructed an artificial neural network (ANN) model and verified its predictive value with immunotherapy response and OS. RESULTS: We defined two groups of ICI-treated glioblastoma patients with large differences in survival benefits as nonresponders (OS ≤6 months, n = 18) and responders (OS ≥17 months, n = 8). No differentially mutated genes were observed between responders and nonresponders. We performed RF analysis to select the most critical responder-relevant features and developed an ANN with 20 input variables, five hidden neurons and one output neuron. Receiver operating characteristic analysis and the DeLong test demonstrated that the ANN had the best performance in predicting responders, with an AUC of 0.97. Survival analysis indicated that ANN-predicted responders had significantly better OS rates than nonresponders. CONCLUSION: The 20-gene panel developed by the ANN could be a promising biomarker for predicting immunotherapy response and prognostic benefits in ICI-treated GBM patients and may guide oncologists to accurately select potential responders for the preferential use of ICIs.

Deep transcranial magnetic stimulation for treatment-resistant depression: A systematic review and meta-analysis of randomized controlled studies.

The efficacy and safety of deep transcranial magnetic stimulation (dTMS) in treating treatment-resistant depression (TRD) are unknown. Up to June 21, 2023, we conducted a systematic search for RCTs, and then extracted and synthesized data using random effects models. Five RCTs involving 507 patients with TRD (243 in the active dTMS group and 264 in the control group) were included in the present study. The active dTMS group showed significantly higher study-defined response rate (45.3% versus 24.2%, n = 507, risk ratio [RR] = 1.87, 95% confidence interval [CI]: 1.21-2.91, I2 = 53%; P = 0.005) and study-defined remission rate (38.3% versus 14.4%, n = 507, RR = 2.37, 95%CI: 1.30-4.32, I2 = 58%; P = 0.005) and superiority in improving depressive symptoms (n = 507, standardized mean difference = -0.65, 95%CI: -1.11--0.18, I2 = 82%; P = 0.006) than the control group. In terms of cognitive functions, no significant differences were observed between the two groups. The two groups also showed similar rates of other adverse events and all-cause discontinuations (P > 0.05). dTMS is an effective and safe treatment strategy for the management of patients with TRD.

Immune landscape and progress in immunotherapy for pituitary neuroendocrine tumors.

Pituitary neuroendocrine tumors (pitNETs) are the second most common primary brain tumors. Despite their prevalence, the tumor immune microenvironment (TIME) and its clinical implications remain largely unexplored. This review provides a comprehensive overview of current knowledge on the immune landscape and advancements in targeted immunotherapy for pitNETs. Macrophages and T cells are principal immune infiltrates within the TIME. Different subtypes of pitNETs display distinct immune patterns, influencing tumor progressive behaviors. PD-L1, the most extensively studied immune checkpoint, is prominently expressed in hormonal pitNETs and correlates with tumor growth and invasion. Cytokines and chemokines including interleukins, CCLs, and CXCLs have complex correlations with tumor subtypes and immune cell infiltration. Crosstalk between macrophages and pitNET cells highlights bidirectional regulatory roles, suggesting potential macrophage-targeted strategies. Recent preclinical studies have demonstrated the efficacy of anti-PD-L1 therapy in a mouse model of corticotroph pitNET. Moreover, anti-PD-1 and/or anti-CTLA-4 immunotherapy has been applied globally in 28 cases of refractory pitNETs, showing more favorable responses in pituitary carcinomas than aggressive pitNETs. In conclusion, the TIME of pitNETs represents a promising avenue for targeted immunotherapy and warrants further investigation.

GRP78 protein metabolism in obese and diabetic rats: a study of its role in metabolic disorders.

OBJECTIVE: This study aimed to compare and analyze the expression and significance of the GRP78 protein in cochlear cell injury induced by a high glucose and high-fat diet in obese and diabetic rats. METHODS: Male SD rats were randomly divided into two groups: normal (NC) and high-fat (HF) groups. The NC group was fed a standard diet for eight weeks, while the HF group received a high-glucose, high-fat diet. The HF group was further categorized into the obesity group (OB group) and the type II diabetes mellitus group (T2DM group). To induce a type II diabetes mellitus (T2DM) model, the T2DM group received an intraperitoneal injection of a small dose of STZ (45 mg/kg). After four weeks on the original diet, body weight, blood glucose, blood lipid levels, and auditory brainstem response (ABR) thresholds were measured. The cochlea was dissected, and its morphology was observed using HE staining. Immunohistochemistry and western blotting were utilized to examine the expression level of the GRP78 protein in the cochlea. RESULTS: (1) The ABR threshold demonstrated a statistically significant difference between the T2DM group and the OB group (P < 0.05), as well as between the OB group and the NC group (P < 0.05). (2) Based on morphological comparisons from HE-stained sections, the T2DM group exhibited the most significant alterations in the number of cells in the spiral ganglion, the organ of Corti, and the stria vascularis of the cochlea. (3) The expression level of the GRP78 protein in the cochlea was higher in the T2DM group compared to the OB group (P < 0.05) and higher in the OB group compared to the NC group (P < 0.05). CONCLUSION: The findings indicate that the GRP78 protein plays a role in hearing loss caused by T2DM and hyperlipidemia. Moreover, T2DM is more likely than hyperlipidemia to be associated with hearing impairment.

Reversibility of Impaired Large-Scale Functional Brain Networks in Cushing's Disease after Surgery Treatment: A Longitudinal Study.

INTRODUCTION: Chronic exposure to excessive endogenous cortisol leads to brain changes in Cushing's disease (CD). However, it remains unclear how CD affects large-scale functional networks (FNs) and whether these effects are reversible after treatment. This study aimed to investigate functional network changes of CD patients and their reversibility in a longitudinal cohort. METHODS: Active CD patients (N = 37) were treated by transsphenoidal pituitary surgery and reexamined 3 months later. FNs were computed from resting-state fMRI data of the CD patients and matched normal controls (NCs, N = 37). A pattern classifier was built on the FNs to distinguish active CD patients from controls and applied to FNs of the CD patients at the 3-month follow-up. Two subgroups of endocrine-remitted CD patients were identified according to their classification scores, referred to as image-based phenotypically (IBP) recovered and unrecovered CD patients, respectively. The informative FNs identified by the classification model were compared between NCs, active CD patients, and endocrine-remitted patients as well as between IBP recovered and unrecovered CD patients to explore their functional network reversibility. RESULTS: All 37 CD patients reached endocrine remission after treatment. The classification model identified three informative FNs, including cerebellar network (CerebN), fronto-parietal network (FPN), and default mode network. Among them, CerebN and FPN partially recovered toward normal at 3 months after treatment. Moreover, the informative FNs were correlated with 24-h urinary-free cortisol and emotion scales in CD patients. CONCLUSION: These findings suggest that CD patients have aberrant FNs that are partially reversible toward normal after treatment.

A Europium Metal-Organic Framework and Its Polymer Composite Membrane as Switch-Off Fluorescence Sensors for Antibiotic Detection in Lake Water.

The detection of antibiotic residues is of great significance in monitoring their overuse in healthcare, livestock and poultry farming, and agricultural production. Herein, EuCl3 and 4,4'-dicarboxyl-diphenoxyethene (H2DPOE) ionothermally reacted in 1-methyl-3-butylimidazolium chloride to give a europium metal-organic framework (Eu-DPOE). Eu-DPOE shows different fluorescence quenching rates for sensing eight antibiotics under different excitation wavelengths. Eu-DPOE displays a fast response, high selectivity, and sensitivity in antibiotic detection by fluorescence quenching. Eu-DPOE can sensitively detect TCs (tetracyclines), NOR (norfloxacin), NFT (furazolidone), ODZ (ornidazole), SDZ (sulfadiazine), and CHL (chloramphenicol) with limits of detection below 0.5 µmol/L. It provides a convenient and rapid tool for sensing antibiotics in aqueous solution. The detection mechanism is a competition absorption between DPOE2- and antibiotics with the supports from powder X-ray diffraction (PXRD), UV-vis spectra, and fluorescence lifetime. With a composite membrane of poly(vinylidene fluoride) (PVDF) matrix loading Eu-DPOE (Eu-DPOE@PVDF), Eu-DPOE@PVDF exhibits a visual fluorescence response to NOR under a 254 nm UV lamp and NFT and CTC under 365 nm. Eu-DPOE@PVDF is applied in the quantitative detection of CTC, NOR, and NFT in lake water with recovery rates ranging from 88.37 to 113.8%. Totally, fluorescence-quenched Eu-DPOE@PVDF exhibits a fast response, high selectivity, and sensitivity in sensing CTC, NOR, and NFT.

Pediatric pituitary neuroendocrine tumors-a 13-year experience in a tertiary center.

Introduction: Pediatric pituitary neuroendocrine tumor is a rare condition, and despite previous research focusing on this specific group, the main factors influencing the surgical cure rate have not been identified. Methods: We conducted a single-center retrospective study on pediatric pituitary neuroendocrine tumor patients who visited Peking Union Medical College Hospital between 2010 and 2023. We collected data on their clinical characteristics, imaging features, surgical outcomes, and follow-up information. Additionally, we used multiple-factor logistic regression to investigate the factors affecting the surgical cure rate of pediatric pituitary neuroendocrine tumor. Results: 232 patients were diagnosed with pediatric pituitary neuroendocrine tumors, with a higher incidence in females. The most common type was ACTH-secreting adenoma (90/232), followed by prolactin-secreting adenoma (63/232), and growth hormone-secreting adenoma (41/232). The majority of pediatric adenomas were macroadenomas (139/232), and some tumors were associated with cystic changes or hemorrhage (58/232), while a few exhibited invasion of the cavernous sinus (33/232). The results of the multivariate analysis indicated that the different hormone secretion types, macroadenoma or the presence of cystic changes or hemorrhage were not significant risk factors for the cure rate after the first surgery. However, the invasion of the cavernous sinus was found to be an important factor influencing the postoperative cure rate. Most pediatric pituitary neuroendocrine tumors with cavernous sinus invasion were macroadenomas, and some displayed characteristics of refractory pituitary neuroendocrine tumors, with some patients experiencing irreversible complications after surgery. Conclusion: Pediatric pituitary neuroendocrine tumors are complex, and the postoperative cure rate is particularly poor for tumors with cavernous sinus invasion. Although macroadenoma itself does not significantly impact the postoperative cure rate, it is still recommended to diagnose and treat early to avoid unnecessary surgery or surgical complications.

Preoperative and postoperative blood testosterone levels in patients with acromegaly: a prospective study.

Purpose: To investigate the prevalence of low blood testosterone level (LTL) and its determinant factors among active male acromegaly patients, as well as the effect of surgery on LTL in male acromegaly patients. Methods: A retrospective, single-center study focused on 252 male acromegaly patients aged 18 years-60 years diagnosed in the Peking Union Medical College Hospital from January 2015 to December 2018 was carried out. The measurements of preoperative and postoperative testosterone levels, serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and other clinical data were analyzed. Results: Forty per cent of subjects included were diagnosed with LTL pre surgery. Patients were divided into normal testosterone level (NTL) and LTL groups based on their testosterone level. There were significant differences (p < 0.01) between groups in the presence of macroadenomas, invasion of the cavernous sinus, compression of the optic chiasm, and serum GH and prolactin levels pre surgery. Invasion of the cavernous sinus [odds ratio (OR) = 4.299; p = 0.000] and serum prolactin level (OR = 1.023, p = 0.001) were independent predictors of LTLs in male patients before surgical intervention. A total of 67.9% of LTL patients recovered during the follow-up, with a new-onset rate of 3.4%. Body mass index, invasion of the cavernous sinus, GH, IGF-1, and prolactin levels, the presence of a prolactin-secreting tumor, and recovery from acromegaly were significantly different (p < 0.05) in the NTL group and in the LTL group during the follow-up. The presence of a prolactin-secreting tumor (OR = 0.224; p = 0.001) and recovery from acromegaly (OR = 0.168; p = 0.006) were independent predictors of LTLs in male acromegaly patients during the follow-up. Conclusion: The invasiveness of tumor and levels of blood prolactin are independent factors for LTLs before surgery, whereas GH and IGF-1 levels are not. Most male patients can recover from LTL after tumor restriction surgery: those who recover from acromegaly have a better chance of recovering from LTL.

Variation in sediment sources and the response of suspended sediment grain size in the upper Changjiang River Basin following the large dam constructions.

The amount, patterns, and particle size composition of suspended sediment in the upper Changjiang Basin has been altered significantly due to the cascade reservoirs construction. A dam breach may disrupt sedimentation in the reservoir, channel erosion downstream of the dam, and the cycle of nutrients and contaminants adherent to the dam. This study is based on the long time-series field data of water discharge, sediment flux, and suspended sediment grain size of the upper Changjiang River Basin from 1973 to 2019. Four significant stepwise reduction periods in sediment load were identified by employing the M-K test, namely, 1973-1992, 1993-2002, 2003-2012, and 2013-2019. Based on the results, sediment load reduction in the upper Changjiang River (CJR) is remarkably correlated with an increase in the capacity of large reservoirs. Jialingjiang River became the largest sediment source area for upper CJR in 2013-2019. Moreover, the variation range of suspended sediment median particle size gradually narrowed with decreasing sediment load during the four periods in the upper CJR. The silt content of suspended sediment increased while clay and sand contents decreased which would maybe a factor of decreasing of P flux in the upper CJR. After the impounding of the Xiangjiaba and Xiluodu Reservoirs in the Jinshajiang River, the fining trend of suspended sediment along the main stem of upper CJR was cut off in 2013-2019, which may be ascribed to sediment management of the cascade reservoirs regulation and the sediment resuspension from the channel erosion in the river downstream. These observations can also serve as a reference for future studies about the effects of cascade reservoirs on aquatic ecology and environmental changes.

Bilateral theta burst stimulation for patients with acute unipolar or bipolar depressive episodes: A systematic review of randomized controlled studies.

OBJECTIVE: This meta-analysis of randomized controlled trials (RCTs) evaluated the overall efficacy and safety of bilateral theta-burst stimulation (TBS) as an intervention for patients with mood disorders. METHODS: A systematic search (up to December 7, 2022) of RCTs was conducted to address the study aims. A random-effects meta-analysis was performed by including study-defined responses and remission as primary outcomes. RESULTS: Analyses included six RCTs comprising 285 participants with major depressive disorder (MDD) (n = 233) or a depressive episode in the course of bipolar disorder (BD) (n = 52) who had undergone active bilateral TBS (n = 142) versus sham stimulation (n = 143). Active bilateral TBS outperformed sham stimulation with respect to study-defined improvements (55.1 % versus 20.3 %, 4 RCTs, n = 152, 95%CI: 1.63 to 4.39, P < 0.0001; I2 = 0 %) and remission rates (37.2 % versus 14.3 %, 2 RCTs, n = 85, 95%CI: 1.13 to 5.95, P = 0.02; I2 = 0 %) in MDD patients but not those with bipolar or unipolar mixed depression. Superiority of active bilateral TBS over sham stimulation was confirmed for improvements in depressive symptoms at post-bilateral TBS assessments and 8-week follow-ups in patients with either MDD or mixed depression (all P < 0.05). Discontinuation rates due to any reason and adverse events (i.e., headache, dizziness) were similar between TBS and sham stimulation groups with MDD or mixed depression (all P > 0.05). CONCLUSION: Bilateral TBS targeting the dorsolateral prefrontal cortex (DLPFC) appears to be a well-tolerated form of repetitive transcranial magnetic stimulation (rTMS) that has substantial antidepressant effects, particularly in patients with MDD. Effects of bilateral TBS on bipolar and unipolar mixed depression should be further investigated.

Adjunctive repetitive transcranial magnetic stimulation for adolescents with first-episode major depressive disorder: a meta-analysis.

Objective: This meta-analysis of randomized clinical trials (RCTs) was conducted to explore the therapeutic effects, tolerability and safety of repetitive transcranial magnetic stimulation (rTMS) as an adjunct treatment in adolescents with first-episode major depressive disorder (FE-MDD). Methods: RCTs examining the efficacy, tolerability and safety of adjunctive rTMS for adolescents with FE-MDD were included. Data were extracted by three independent authors and synthesized using RevMan 5.3 software with a random effects model. Results: A total of six RCTs involving 562 adolescents with FE-MDD were included. Adjunctive rTMS was superior in improving depressive symptoms over the control group [standardized mean difference (SMD) = -1.50, 95% confidence interval (CI): -2.16, -0.84; I2 = 89%, p < 0.00001] in adolescents with FE-MDD. A sensitivity analysis and two subgroup analyses also confirmed the significant findings. Adolescents with FE-MDD treated with rTMS had significantly greater response [risk ratio (RR) = 1.35, 95% CI: 1.04, 1.76; I2 = 56%, p = 0.03] and remission (RR = 1.35, 95% CI: 1.03, 1.77; I2 = 0%, p = 0.03) over the control group. All-cause discontinuations were similar between the two groups (RR = 0.79, 95% CI: 0.32, 1.93; I2 = 0%, p = 0.60). No significant differences were found regarding adverse events, including headache, loss of appetite, dizziness and nausea (p = 0.14-0.82). Four out of six RCTs (66.7%), showed that adjunctive rTMS was more efficacious over the control group in improving neurocognitive function (all p < 0.05). Conclusion: Adjunctive rTMS appears to be a beneficial strategy in improving depressive symptoms and neurocognitive function in adolescents with FE-MDD. Higher quality RCTs with larger sample sizes and longer follow-up periods are warranted in the future.

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review.

Objective: Intermittent theta-burst stimulation (iTBS), which is a form of repetitive transcranial magnetic stimulation (rTMS), can produce 600 pulses to the left dorsolateral prefrontal cortex (DLPFC) in a stimulation time of just over 3 min. The objective of this systematic review was to compare the safety and efficacy of iTBS and high-frequency (≥ 5 Hz) rTMS (HF-rTMS) for patients with treatment-resistant depression (TRD). Methods: Randomized controlled trials (RCTs) comparing the efficacy and safety of iTBS and HF-rTMS were identified by searching English and Chinese databases. The primary outcomes were study-defined response and remission. Results: Two RCTs (n = 474) investigating the efficacy and safety of adjunctive iTBS (n = 239) versus HF-rTMS (n = 235) for adult patients with TRD met the inclusion criteria. Among the two included studies (Jadad score = 5), all were classified as high quality. No group differences were found regarding the overall rates of response (iTBS group: 48.0% versus HF-rTMS group: 45.5%) and remission (iTBS group: 30.0% versus HF-rTMS group: 25.2%; all Ps > 0.05). The rates of discontinuation and adverse events such as headache were similar between the two groups (all Ps > 0.05). Conclusion: The antidepressant effects and safety of iTBS and HF-rTMS appeared to be similar for patients with TRD, although additional RCTs with rigorous methodology are needed.