Sigma-1 receptor exerts protective effects on ameliorating nephrolithiasis by modulating endoplasmic reticulum-mitochondrion association and inhibiting endoplasmic reticulum stress-induced apoptosis in renal tubular epithelial cells.

Oxalate-induced damage to renal tubular epithelial cells (RTECs) is an essential factor in the incident kidney stone, but the specific mechanism is unclear. Recent research has pinpointed interacting areas within the endoplasmic reticulum and mitochondria, called mitochondria-associated membranes (MAMs). These studies have linked endoplasmic reticulum stress (ERS) and oxidative imbalance to kidney disease development. The sigma-1 receptor (S1R), a specific protein found in MAMs, is involved in various physiological processes, but its role in oxalate-induced kidney stone formation remains unclear. In this study, we established cellular and rat models of oxalate-induced kidney stone formation to elucidate the S1R's effects against ERS and apoptosis and its mechanism in oxalate-induced RTEC injury. We found that oxalate downregulated S1R expression in RTECs and escalated oxidative stress and ERS, culminating in increased apoptosis. The S1R agonist dimemorfan up-regulated S1R expression and mitigated ERS and oxidative stress, thereby reducing apoptosis. This protective effect was mediated through S1R inhibition of the CHOP pathway. Animal experiments demonstrated that S1R's activation attenuated oxalate-induced kidney injury and alleviated kidney stone formation. This is the first study to establish the connection between S1R and kidney stones, suggesting S1R's protective role in inhibiting ERS-mediated apoptosis to ameliorate kidney stone formation.

Oxalate regulates crystal-cell adhesion and macrophage metabolism via JPT2/PI3K/AKT signaling to promote the progression of kidney stones.

Oxalate is an organic dicarboxylic acid that is a common component of plant foods. The kidneys are essential organs for oxalate excretion, but excessive oxalates may induce kidney stones. Jupiter microtubule associated homolog 2 (JPT2) is a critical molecule in Ca2+ mobilization, and its intrinsic mechanism in oxalate exposure and kidney stones remains unclear. This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones. Genetic approaches were used to control JPT2 expression in cells and mice, and the JPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics. The results showed that oxalate exposure triggered the upregulation of JPT2, which is involved in nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated Ca2+ mobilization. Transcriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown, and these were dominated by phosphatidylinositol 3-kinase (PI3K)/AKT signaling, respectively. Untargeted metabolomics indicated that JPT2 knockdown inhibited the production of succinic acid semialdehyde (SSA) in macrophages. Furthermore, JPT2 deficiency in mice inhibited kidney stones mineralization. In conclusion, this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion, and modulating macrophage metabolism and inflammatory polarization via JPT2/PI3K/AKT signaling.

[3 + 2] Cycloaddition Reaction of Vinylsulfonium Salts with Hydrazonoyl Halides: Synthesis of Pyrazoles.

An efficient [3 + 2] cycloaddition reaction between in situ generated nitrile imines from hydrazonoyl halides and vinylsulfonium salts is developed. The nitrile imines are demonstrated to be a new class of reaction partner for vinylsulfonium salts to conduct the [3 + 2] cycloaddition reaction. The process provides a concise and efficient method for the construction of pyrazole derivatives under mild reaction conditions with broad substrate scope, good product yields, and high regioselectivity.

Synthesis of Fully Substituted Difluoromethylpyrazoles by Cyclization of Difluoroacetohydrazonoyl Bromides with 2-Acylacetonitriles or Malononitrile.

A concise and efficient method for the construction of fully substituted difluoromethylpyrazoles is achieved by a cyclization reaction between difluoroacetohydrazonoyl bromides and 2-acylacetonitrile or malononitrile. The method features advantages such as mild reaction conditions, broad substrate scope, good product yields, and high regioselectivity.

Serum metabolomics study reveals a distinct metabolic diagnostic model for renal calculi.

Renal calculi (RC) represent a prevalent disease of the urinary system characterized by a high incidence rate. The traditional clinical diagnosis of RC emphasizes imaging and stone composition analysis. However, the significance of metabolic status in RC diagnosis and prevention remains unclear. This study aimed to investigate serum metabolites in RC patients to identify those associated with RC and to develop a metabolite-based diagnostic model. We employed nontargeted metabolomics utilizing ultra-performance liquid chromatography‒mass spectrometry (UPLC‒MS) to compare serum metabolites between RC patients and healthy controls. Our findings demonstrated significant disparities in serum metabolites, particularly in fatty acids and glycerophospholipids, between the two groups. Notably, the glycerophospholipid (GP) metabolic pathway in RC patients was significantly disrupted. Logistic regression models using differentially abundant metabolites revealed that elevated levels of 2-butyl-4-methyl phenol and reduced levels of phosphatidylethanolamine (P-16:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)) had the most substantial effect on RC risk. Overall, our study indicates that RC induces notable alterations in serum metabolites and that the diagnostic model based on these metabolites effectively distinguishes RC. This research offers promising insights and directions for further diagnostic and mechanistic studies on RC.

Synthesis of difluoromethylated spiropyrazolones via [3 + 2] cycloaddition of difluoroacetohydrazonoyl bromides with alkylidene pyrazolones.

An effective [3 + 2] cycloaddition reaction of difluoromethyl or trifluoromethyl hydrazonoyl bromides with alkylidene pyrazolones was disclosed. This method provides an efficient approach for accessing a variety of highly functionalized fluoroalkyl spiropyrazolones in good yields. This protocol also features some advantages such as easily available and stable substrates, simple operation procedures, and atom and step economy. The formation of (cis)- and (trans)-products was discussed.

Understanding formation processes of calcareous nephrolithiasis in renal interstitium and tubule lumen.

Kidney stone, one of the oldest known diseases, has plagued humans for centuries, consistently imposing a heavy burden on patients and healthcare systems worldwide due to their high incidence and recurrence rates. Advancements in endoscopy, imaging, genetics, molecular biology and bioinformatics have led to a deeper and more comprehensive understanding of the mechanism behind nephrolithiasis. Kidney stone formation is a complex, multi-step and long-term process involving the transformation of stone-forming salts from free ions into asymptomatic or symptomatic stones influenced by physical, chemical and biological factors. Among the various types of kidney stones observed in clinical practice, calcareous nephrolithiasis is currently the most common and exhibits the most intricate formation mechanism. Extensive research suggests that calcareous nephrolithiasis primarily originates from interstitial subepithelial calcified plaques and/or calcified blockages in the openings of collecting ducts. These calcified plaques and blockages eventually come into contact with urine in the renal pelvis, serving as a nidus for crystal formation and subsequent stone growth. Both pathways of stone formation share similar mechanisms, such as the drive of abnormal urine composition, involvement of oxidative stress and inflammation, and an imbalance of stone inhibitors and promoters. However, they also possess unique characteristics. Hence, this review aims to provide detailed description and present recent discoveries regarding the formation processes of calcareous nephrolithiasis from two distinct birthplaces: renal interstitium and tubule lumen.

Macrophage-to-myofibroblast transition promotes pulmonary fibrosis occurred in LPS-induced acute lung injury of mouse models / 基础医学与临床

Objective To explore the impact of macrophage-to-myofibroblast transition(MMT)on pulmonary fibro-sis induced by acute lung injury by LPS.Methods Totally 21 male mice were randomly classified into 7 groups:control group,model group(LPS-PF)at different time points and intervention group of clodronate-liposomes(CL-LIP)treatement at different time points(n=3).Pulmonary fibrosis was identified by HE and Masson staining microscopy.The immuno-fluorescence technology was used for the evaluation of numbers of macrophage-to-myofi-broblast transition cells(MMT cell which co-expressed CD68 and α-SMA).Bone marrow-derived macrophages(BMDMs)were randomly classified into two group:control(Ctrl)group and TGF-β1-treated group induced by transforming growthfactor-β1.α-SMA,FN and Col1 were detected by RT-qPCR.The expression of α-SMA,Smad3 and p-Smad3 protein was evaluated by Western blot.Results At day 7,the Ashcroft score of lung tissue in LPS-PF mouse model was significantly increased when compared with the Ctrl group(P＜0.01);While the score signifi-cantly declined when the model was pretreated with CL-LIP(P＜0.05).As detected by immuno-fluorescence stai-ning,in CL-LIP group the number of CD68-positive cells co-labeled with α-SMA was obviously less then that of LPS-PF group of the corresponding time point(P＜0.01).When the BMDMs were stimulated by TGF-β1 at 24 h,48 h and 96 h respectively,a higher expression of α-SMA,FN,Col1,were found in TGF-β1-treated group than that in Ctrl group at the corresponding time point(P＜0.01).The expression of Smad3,p-Smad3 significantly higher in LPS-PF group(at both day 7 and day 10)and TGF-β1-treated group(at both 48 h and 96 h)as compared to cor-responding control group(P＜0.01).Conclusions MMT promotes pulmonary fibrosis induced by ALI via LPS.Smad3 is proved to be involved in the MMT process.

Ultra-high dose rate FLASH irradiation reduces radiation-induced intestinal injury in mice / 中华放射肿瘤学杂志

Objective:To investigate whether ultra-high dose rate (FLASH) irradiation can reduce radiation-induced intestinal injuries of mice compared to conventional dose rate (CONV) irradiation.Methods:Both FLASH and CONV irradiation were delivered with electron beam, with dose rates of 750 Gy/s and 0.5G y/s, respectively. A total of 105 mice were randomly divided into groups using a simple randomization method. Twenty-one mice were selected for weight observation, 7 mice in each group. After 9 Gy FLASH and CONV irradiation on the abdomen, the weight changes of mice were measured every other day, and compared among three groups. Twenty-four mice were selected for pathological examination including 5 mice in the control group. Three-and-a-half-day days after 12 Gy FLASH ( n=10) and CONV irradiation ( n=9) on the abdomen, the intestines of the mice were taken. Pathological sections were stained with hematoxylin-eosin (HE) to compare the number and percentage of regenerated crypts of the small intestine between two groups. After 12 Gy FLASH ( n=10) and CONV irradiation ( n=10) on the abdomen, the survival of 20 mice was observed. After FLASH using 4.5 Gy×2 times ( n=10) and CONV irradiation at 9 Gy×1 time ( n=10) on the abdomen, the weight changes were observed. After FLASH using 6 Gy×2 times ( n=10) and CONV irradiation at 12 Gy×1 time ( n=10) on the abdomen, the survival of mice was observed. The time interval between two irradiation was 1 min. EBT3 film was employed to monitor the actual exposure dose of the mice. The variables conforming to normal distribution were expressed by Mean±SD. Inter group comparison was performed by independent t-test. The survival of mice among different groups was compared by log-rank test. Results:After 9 Gy of abdominal irradiation, the mean weight of mice in the FLASH group was significantly higher than that in the CONV group. The weight of mice in the FLASH and CONV groups was (19.8±0.8) g and (18.0±1.8)g ( P=0.036) at 7 days after irradiation, (22.0±1.0)g and (21.2±0.5)g ( P=0.075) at 15 days after irradiation, and (24.2±1.4)g and (22.0±1.2)g ( P=0.012) at 25 days after irradiation, respectively. After 12 Gy irradiation, the mean survival of mice in FLASH and CONV groups was 4 days and 4.7 days ( P=0.029). After 12 Gy total abdominal irradiation, the mean number of intestinal regenerative crypts in the FLASH and CONV groups was 2.9/mm and 1.2/mm ( P=0.041), and the percentage of intestinal regenerative crypts was 34.1% and 14.1%, respectively. The survival of mice irradiated by FLASH using 6 Gy×2 times was longer compared with that of mice after CONV irradiation at 12 Gy×1 time. The weight of mice after 4.5 Gy×2 times irradiation was higher than that of mice after CONV irradiation at 9 Gy×1 time. Conclusion:Weight, survival and the number of intestinal regenerative crypts in the FLASH group are higher than those in the CONV group after irradiation, indicating that radiation-induced intestinal injury caused by FLASH irradiation is slighter than that of CONV irradiation.

Research progress in moderately hypofractionated radiotherapy for cancer / 中华放射肿瘤学杂志

Radiotherapy is one of the important treatment modalities for malignant tumors. Conventional fractionation is the most commonly-used radiotherapy mode, but it has disadvantages such as long treatment time and low efficiency, etc. With the advancement of radiotherapy equipment and technology, moderately hypofractionated radiotherapy has become the standard treatment for tumors such as breast cancer and prostate cancer, etc. However, the efficacy and safety of moderately hypofractionated radiotherapy have not been fully confirmed in a wider range of tumors. In this article, the application, efficacy, and safety of moderately hypofractionated radiotherapy in malignant tumors were reviewed.

Research progress of ozone therapy in treatment of novel coronavirus infection / 中华全科医师杂志

Recent studies have shown that ozone therapy, a widely used immunotherapy in various diseases, can play a therapeutic role in the novel coronavirus infection by enhancing lung function, reducing inflammatory reactions, and bolstering immune system performance. This article reviews the pathophysiological basis of novel coronavirus infection and the mechanisms involved in ozone therapy for its treatment, also summarizes the clinical evidence and safety assessment of ozone therapy in combating novel coronavirus infections.

Transcutaneous Electrical Acupoint Stimulation Promotes PGC-1α Mediated Mitochondrial Biogenesis and Antioxidant Stress to Protect Cognitive Function in Vascular Dementia Rats / 生物化学与生物物理进展

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

Intravenous immunoglobulin for treatment of hospitalized COVID-19 patients: an evidence mapping and meta-analysis.

BACKGROUND: The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. METHODS: Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. RESULTS: We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI - 2.56, 3.31) and ICU (MD 0.36; 95% CI - 0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). CONCLUSION: Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted.

Tandem Addition/Cyclization/Halogenation Reaction of Difluoromethylated N-Acylhydrazones with Allyltrimethylsilanes.

As novel difluoromethyl building blocks, difluoromethylated N-acylhydrazones react with allyltrimethylsilanes and the halogen source via a tandem addition/cyclization/halogenation strategy, which produces various difluoromethylpyrazoline compounds in good yields. The method features mild reaction conditions, broad substrate scopes, and a transition metal-free process with easy operation. It also proves that difluoromethylated N-acylhydrazones are useful difluoromethyl building blocks for the construction of difluoromethylated nitrogen heterocycles.

The cyclization/rearrangement of α-hydroxy ketones with trifluoromethyl N-acylhydrazones to synthesize multi-substituted trifluoromethyloxazolines.

A highly efficient and metal-free [3+2] cyclization/rearrangement reaction toward the synthesis of multisubstituted trifluoromethyloxazolines from α-hydroxyketones and trifluoromethyl N-acylhydrazones has been developed. The unprecedented rearrangement of the amide fragment under acidic conditions after cleavage of the N-N bond of acylhydrazones has opened up new avenues for the development of reactions involving trifluoromethyl N-acylhydrazones. DFT calculations show that the mechanism involves multiple proton transfer processes.

International experts consensus guidelines on robotic liver resection in 2023.

The robotic liver resection (RLR) has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system, however, controversies still exist. Based on the foundation of the previous consensus statement, this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice. The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine (EBM). Relevant literature was reviewed and analyzed by the evidence evaluation group. According to the WHO Handbook for Guideline Development, the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022, a total of 14 recommendations were generated. Among them were 8 recommendations formulated by the GRADE method, and the remaining 6 recommendations were formulated based on literature review and experts' opinion due to insufficient EBM results. This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.

Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese and Western medicine.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Melatonin exerts a protective effect in ameliorating nephrolithiasis via targeting AMPK/PINK1-Parkin mediated mitophagy and inhibiting ferroptosis in vivo and in vitro.

Hyperoxaluria-induced damage to renal tubular epithelial cells (RTECs) is considered the most significant contributor to kidney stone formation. However, the precise regulatory mechanism underlying this damage, particularly its association with mitophagy dysfunction, remains unclear. Additionally, effective preventive medications for kidney stones are lacking. Melatonin, a hormone secreted by the pituitary gland that primarily regulates circadian rhythm, has been found to modulate mitophagy in recent research. Therefore, this investigation aims to examine the impact of melatonin on mitophagy and cellular impairment in the formation of kidney stone. The results of this study reveal that melatonin can alleviate the formation of kidney stones and reduce oxalate-induced renal injuries. In the RTECs of kidney stone model, mitophagy was found to be impaired, leading to increased oxidative stress, inflammation, and ferroptosis both in vivo and in vitro. Melatonin was shown to have a restorative potential in enhancing PINK1-Parkin-regulated mitophagy through AMPK phosphorylation, reducing excessive ROS release and inhibiting oxidative stress, inflammation and ferroptosis. Further experiments demonstrated that the protective effect of melatonin was diminished by PINK1 knockdown and AMPK pathway blockade. This study is the first to reveal the interplay between mitophagy and ferroptosis in kidney stone models and establish the protective role of melatonin in restoring mitophagy to inhibit ferroptosis.

Building a nomogram plot based on the nanopore targeted sequencing for predicting urinary tract pathogens and differentiating from colonizing bacteria.

Background: The identification of uropathogens (UPBs) and urinary tract colonizing bacteria (UCB) conduces to guide the antimicrobial therapy to reduce resistant bacterial strains and study urinary microbiota. This study established a nomogram based on the nanopore-targeted sequencing (NTS) and other infectious risk factors to distinguish UPB from UCB. Methods: Basic information, medical history, and multiple urine test results were continuously collected and analyzed by least absolute shrinkage and selection operator (LASSO) regression, and multivariate logistic regression was used to determine the independent predictors and construct nomogram. Receiver operating characteristics, area under the curve, decision curve analysis, and calibration curves were used to evaluate the performance of the nomogram. Results: In this study, the UPB detected by NTS accounted for 74.1% (401/541) of all urinary tract microorganisms. The distribution of ln(reads) between UPB and UCB groups showed significant difference (OR = 1.39; 95% CI, 1.246-1.551, p < 0.001); the reads number in NTS reports could be used for the preliminary determination of UPB (AUC=0.668) with corresponding cutoff values being 7.042. Regression analysis was performed to determine independent predictors and construct a nomogram, with variables ranked by importance as ln(reads) and the number of microbial species in the urinary tract of NTS, urine culture, age, urological neoplasms, nitrite, and glycosuria. The calibration curve showed an agreement between the predicted and observed probabilities of the nomogram. The decision curve analysis represented that the nomogram would benefit clinical interventions. The performance of nomogram with ln(reads) (AUC = 0.767; 95% CI, 0.726-0.807) was significantly better (Z = 2.304, p-value = 0.021) than that without ln(reads) (AUC = 0.727; 95% CI, 0.681-0.772). The rate of UPB identification of nomogram was significantly higher than that of ln(reads) only (χ2 = 7.36, p-value = 0.009). Conclusions: NTS is conducive to distinguish uropathogens from colonizing bacteria, and the nomogram based on NTS and multiple independent predictors has better prediction performance of uropathogens.

Transversus thoracic muscle plane block for pain during cardiac surgery: a systematic review and meta-analysis.

STUDY OBJECTIVE: The role of transversus thoracic muscle plane blocks (TTMPBs) during cardiac surgery is controversial. We conducted a systematic review to establish the effectiveness of this procedure. DESIGN: Systematic review. We searched PubMed, Embase, Web of Science, CENTRAL, WanFang Data, and the China National Knowledge Infrastructure to June 2022, and followed the GRADE approach to evaluate the certainty of evidence. STUDY ELIGIBILITY CRITERIA: Eligible studies enrolled adult patients scheduled to undergo cardiac surgery and randomized them to receive a TTMPB or no block/sham block. MAIN RESULTS: Nine trials that enrolled 454 participants were included. Compared to no block/sham block, moderate certainty evidence found that TTMPB probably reduces postoperative pain at rest at 12 h [weighted mean difference (WMD) -1.51 cm on a 10 cm visual analogue scale for pain, 95% CI -2.02 to -1.00; risk difference (RD) for achieving mild pain or less (≤3 cm), 41%, 95% CI 17-65) and 24 h (WMD -1.07 cm, 95% CI -1.83 to -0.32; RD 26%, 95% CI 9-37). Moderate certainty evidence also supported that TTMPB probably reduces pain during movement at 12 h (WMD -3.42 cm, 95% CI -4.47 to -2.37; RD 46%, 95% CI 12-80) and at 24 h (WMD -1.73 cm, 95% CI -3.24 to -0.21; RD 32%, 95% CI 5-59), intraoperative opioid use [WMD -28 milligram morphine equivalent (MME), 95% CI -42 to -15], postoperative opioid consumption (WMD -17 MME, 95% CI -29 to -5), postoperative nausea and vomiting (absolute risk difference 255 less per 1000 persons, 95% CI 140-314), and intensive care unit (ICU) length of stay (WMD -13 h, 95% CI -21 to -6). CONCLUSION: Moderate certainty evidence showed TTMPB during cardiac surgery probably reduces postoperative pain at rest and with movement, opioid consumption, ICU length of stay, and the incidence of nausea and vomiting.