Gut microbiota modulating intestinal stem cell differentiation.

Proliferation and differentiation of intestinal stem cell (ISC) to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation. However, when this disordered proliferation continues, it induces the ISC to enter a cancerous state. The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis. Microbiota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors, while in steady state, differentiated colonocytes are able to break down such metabolites, thereby protecting stem cells at the gut crypt. In the future, the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.

The optimal atropine concentration for myopia control in Chinese children: a systematic review and network Meta-analysis.

AIM: To figure out whether various atropine dosages may slow the progression of myopia in Chinese kids and teenagers and to determine the optimal atropine concentration for effectively slowing the progression of myopia. METHODS: A systematic search was conducted across the Cochrane Library, PubMed, Web of Science, EMBASE, CNKI, CBM, VIP, and Wanfang database, encompassing literature on slowing progression of myopia with varying atropine concentrations from database inception to January 17, 2024. Data extraction and quality assessment were performed, and a network Meta-analysis was executed using Stata version 14.0 Software. Results were visually represented through graphs. RESULTS: Fourteen papers comprising 2475 cases were included; five different concentrations of atropine solution were used. The network Meta-analysis, along with the surface under the cumulative ranking curve (SUCRA), showed that 1% atropine (100%)>0.05% atropine (74.9%) >0.025% atropine (51.6%)>0.02% atropine (47.9%)>0.01% atropine (25.6%)>control in refraction change and 1% atropine (98.7%)>0.05% atropine (70.4%)>0.02% atropine (61.4%)>0.025% atropine (42%)>0.01% atropine (27.4%)>control in axial length (AL) change. CONCLUSION: In Chinese children and teenagers, the five various concentrations of atropine can reduce the progression of myopia. Although the network Meta-analysis showed that 1% atropine is the best one for controlling refraction and AL change, there is a high incidence of adverse effects with the use of 1% atropine. Therefore, we suggest that 0.05% atropine is optimal for Chinese children to slow myopia progression.

Characteristics and treatment of midlife-onset epilepsy: A 24-year single-center, retrospective study.

OBJECTIVE: This study aimed to analyze the clinical characteristics, etiology, and treatment of midlife-onset epilepsy in a real-world setting at a single center in China. METHODS: The clinical data of patients who attended the epilepsy clinic of the Department of Neurology, First Medical Center of Chinese PLA General Hospital from February 1999 to March 2023 were retrospectively analyzed. The clinical characteristics, etiology, and risk factors for midlife-onset epilepsy over the past 24 years were analyzed. RESULTS: Of the 969 patients with onset at 45-64 years of age, 914 were diagnosed with epilepsy with at least two unprovoked seizures 24 h apart. Of those, 99.7% (911) were of focal origin. The median duration from the initial seizure to follow-up treatment was 2 months (interquartile range [IQR]: 1.0-6.0 months). Before commencing treatment, 30.2% (207/683) of patients experienced more than two seizures. A structural etiology was found in 66.3% (606/914) of patients. Cerebrovascular disease (CVD) and traumatic brain injury (TBI) accounted for 19.9% (182/914) and 16.6% (152/914) of the cases, respectively. Logistic regression analysis showed that patients with abnormal imaging (odds ratio [OR] 2.04; 95% confidence interval [CI] 1.25-3.32; p = .004), focal seizures (OR 2.98; 95%CI 1.82-4.87; p < .001), and seizure clusters (OR 2.40; 95%CI 1.21-4.73; p = .01) had poor drug responses. Treatment outcomes were generally better in patients with epilepsy after CVD (OR .49; 95%CI .28-.85; p = .01). Treatment initiation after two seizures (OR .70; 95%CI .42-1.15; p = .16) or 6 months after the first seizure (OR 1.17; 95%CI .66-2.09; p = .58) did not result in poor drug effectiveness. SIGNIFICANCE: Midlife-onset epilepsy is typically of focal etiology, with CVD being the most common cause, and tends to respond well to medication. The median duration from the initial seizure to follow-up treatment was 2 months. Over 30% of patients experienced more than two seizures before commencing treatment, but this did not affect subsequent outcomes.

Odorant-binding protein CrufOBP1 in Cotesia ruficrus females plays a pivotal role in the detection of Spodoptera frugiperda larvae.

Cotesia ruficrus presents a promising local natural enemy for controlling the invasive fall armyworm Spodoptera frugiperda in China. However, the mechanisms underlying how C. ruficrus locates its target pest remain unclear. In this study, we analyzed the expression patterns of 18 CrufOBPs across different developmental stages of C. ruficrus, and found that CrufOBP1 exhibited consistent and high expression levels in female adults. CrufOBP1 transcript was predominantly localized in sensilla placodea and sensilla trichodea on the antennae. Additionally, we confirmed the binding properties of CrufOBP1 protein to various cuticular compounds of S. frugiperda larvae. Subsequent electroantennogram and behavioral assays revealed that 1-(2-hydroxy-5-methylphenyl)-ethanone attracted female C. ruficrus, consequently increased the parasitism rate. However, upon silencing CrufOBP1, females exhibited reduced attraction towards 1-(2-hydroxy-5-methylphenyl)-ethanone, indicating the crucial role of CrufOBP1 in the chemoreception of C. ruficrus. These findings shed light on the kairomone-based mechanism employed by C. ruficrus to locate S. frugiperda larvae and hold a promise for the development of environmentally friendly pest management strategies.

Research progress in the treatment of schistosomiasis with traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health. Schistosomiasis has been a widespread issue in China for at least 2000 years. Traditional Chinese medicine (TCM) has a rich history of treating this disease, and the significant theoretical and practical knowledge attained therein may be useful in modern practice. AIM OF THE STUDY: To comprehensively review TCM for the treatment of schistosomiasis, summarize the molecular basis, mechanism of action, active ingredients and formulas of TCM, and clarify the value of TCM for expanding drug options for the clinical treatment of schistosomiasis. MATERIALS AND METHODS: In PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases, "Schistosomiasis", "Schistosoma mansoni", "Schistosoma japonicum", "Liver fibrosis" and "Granuloma" were used as the key words. Information related to in vivo animal studies and clinical studies of TCM for the treatment of schistosomiasis in the past 25 years was retrieved, and the inclusion criteria focused on medicinal plants that had a history of use in China. RESULTS: In this study, we collected and organized a large amount of literature on the treatment of schistosomiasis by TCM. TCM exerts therapeutic effects through antischistosomal and immunomodulatory effects, suppresses HSC activation and proliferation, reduces ECM deposition, and inhibits oxidative stress and other activities. The treatment of schistosomiasis by TCM has a unique advantage, especially for the treatment of schistosomal liver fibrosis, and the treatment of schistosomiasis with TCM in combination with praziquantel is superior to monotherapy. CONCLUSION: Schistosomiasis remains a global public health problem, and TCM has made significant progress in the prevention and treatment of schistosomiasis and is a potential source of drugs for the treatment of schistosomiasis. However, research on drug screening and the mechanism of action of TCM for the treatment of schistosomiasis is lacking, and further studies and research are needed.

MiRNA-224-5p regulates the defective permeability barrier in sensitive skin by targeting claudin-5.

BACKGROUND: Sensitive skin is hypersensitive to various external stimuli and a defective epidermal permeability barrier is an important clinical feature of sensitive skin. Claudin-5 (CLDN5) expression levels decrease in sensitive skin. This study aimed to explore the impact of CLDN5 deficiency on the permeability barrier in sensitive skin and the regulatory role of miRNAs in CLDN5 expression. MATERIALS AND METHODS: A total of 26 patients were retrospectively enrolled, and the CLDN5 expression and permeability barrier dysfunction in vitro were assessed. Then miRNA-224-5p expression was also assessed in sensitive skin. RESULTS: Immunofluorescence and electron microscopy revealed reduced CLDN5 expression, increased miR-224-5p expression, and disrupted intercellular junctions in sensitive skin. CLDN5 knockdown was associated with lower transepithelial electrical resistance (TEER) and Lucifer yellow penetration in keratinocytes and organotypic skin models. The RNA-seq and qRT-PCR results indicated elevated miR-224-5p expression in sensitive skin; MiR-224-5p directly interacted with the 3`UTR of CLDN5, resulting in CLDN5 deficiency in the luciferase reporter assay. Finally, miR-224-5p reduced TEER in keratinocyte cultures. CONCLUSION: These results suggest that the miR-224-5p-induced reduction in CLDN5 expression leads to impaired permeability barrier function, and that miR-224-5p could be a potential therapeutic target for sensitive skin.

Global prevalence of depression in menopausal women: A systematic review and meta-analysis.

BACKGROUND: An association between the menopause and depression is widely reported. This review aims to determine the global prevalence of depression in menopausal women (this includes women in perimenopause and postmenopause). METHODS: PubMed, Web of Science, Embase, and PsycINFO databases were systematically searched from database inception until March 1, 2024. Studies with validated methods for assessing the prevalence of depression in perimenopausal and postmenopausal women were included. Two authors independently extracted relevant data. Random effects meta-analysis and Meta-regression analysis were performed using Stata software. RESULTS: Total of 55 studies (76,817 participants) were included in the review. A random effects model was used to calculate pooled prevalence. The pooled depression prevalence in menopausal women was 35.6 % (95 % CI: 32.0-39.2 %), with 33.9 % (95 % CI: 27.8-40.0 %) in perimenopausal women, and 34.9 % (95 % CI: 30.7-39.1 %) in postmenopausal women. Subgroup analyses indicated that region, screening tool, study design, and setting moderated the prevalence of depression. Meta-regression indicated that smaller sample sizes and poorer study quality were significantly associated with a higher prevalence. LIMITATIONS: There was a high degree of heterogeneity across the included studies. Only articles published in English were included. There was significant publication bias in this meta-analysis. There is insufficient information about many risk factors of menopausal depression in current meta-analysis. CONCLUSIONS: Depression is common among menopausal women worldwide. To reduce the negative impact of depression on health outcomes in menopausal women, regular screening and the availability of effective prevention and treatment measures should be made available for this population.

Yingxiang Acupoint Embedding Improves Mucosal Barrier Function in Rats with Local Allergic Rhinitis.

INTRODUCTION: Epithelial barrier disruption is the initial cause of various diseases. We previously reported that acupoint catgut embedding (AE) improves tight junction proteins (TJs) in rats with allergic rhinitis. However, whether AE improves the epithelial barrier in local allergic rhinitis (LAR) remains unknown. METHODS: A total of 36 Sprague Dawley (SD) male rats aged 5-7 weeks were divided into 6 groups with 6 rats each: control group, LAR model group, false acupoint embedding + LAR group, acupoint embedding + LAR group, capsaicin + LAR group, and tunicamycin + acupoint embedding + LAR group. Behavioral observation, ELISA to detect inflammatory factors in nasal lavage fluid and serum IgE, nasal mucosal permeability test, hematoxylin-eosin staining, PCR to detect Substance P (SP), Western blot, and immunofluorescence to detect endoplasmic reticulum stress (ERS) index and TJs were used to investigate the mechanism of AE in LAR. RESULTS: AE improved the symptoms and pathological features of nasal mucosa of LAR rats, reduced the inflammatory factors (IL4, IL5, IL13) of nasal lavage fluid, and showed no significant change in serum IgE levels in all groups. In addition, AE decreased the expression of SP in nasal mucosa of LAR rats, inhibited ERS, increased the expression of tight junction protein, reduced the permeability of nasal mucosa, and improved the function of nasal mucosal barrier. CONCLUSION: This study confirms that AE can improve the nasal mucosal barrier function of LAR by reducing the expression of SP, inhibiting ERS and increasing the expression of TJs, thus enhancing the nasal mucosal barrier function.

Clinical and structural characteristics of NEU1 variants causing sialidosis type 1.

Purpose: Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying NEU1 variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. Methods: First, whole-exome sequencing and detailed clinical examination were performed on the family. Second, structural analysis, including energy, flexibility and polar contacts, was conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. Results: We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by sialidase activity assay. The cherry-red spot was more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal EEGs and VEPs had a relatively early age of onset, whereas patients with myoclonus had a late onset. Conclusion: Changes in flexibility and local polar contacts may be indicators of the NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.

[Identification and visual analysis of ginsenosides in multi-steamed roots of Panax quinquefolium based on UPLC-Q-TOF-MS/MS and MALDI-MSI].

This study aims to investigate the component variations and spatial distribution of ginsenosides in Panax quinquefolium roots during repeated steaming and drying. Ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to identify the ginsenosides in the root extract. Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) was employed to visualize the spatial distribution and spatiotemporal changes of prototype ginsenosides and metabolites in P. quinquefolium roots. The UPLC results showed that 90 ginsenosides were identified during the steaming process of the roots, and polar ginsenosides were converted into low polar or non-polar ginsenosides. The content of prototype ginsenosides decreased, while that of rare ginsenosides increased, which included 20(S/R)-ginsenoside Rg_3, 20(S/R)-ginsenoside Rh_2, and ginsenosides Rk_1, Rg_5, Rs_5, and Rs_4. MALDI-MSI results showed that ginsenosides were mainly distributed in the epidermis and phloem. As the steaming times increased, ginsenosides were transported to the xylem and medulla. This study provides fundamental information for revealing the changes of biological activity and pharmacological effect of P. quinquefolium roots that are caused by repeated steaming and drying and gives a reference for expanding the application scope of this herbal medicine.

Probing cell metabolism using the two-photon excitation autofluorescence lifetime of tryptophan.

Compared to intensity detection, fluorescence lifetime has the advantage of being unaffected by variations in excitation intensity, fluorophore concentration, or attenuation due to biological absorption and scattering. In this Letter, to the best of our knowledge, we present the use of the two-photon excitation autofluorescence lifetime imaging of tryptophan (TRP) to probe cell metabolism for the first time. Tests of pure chemical samples showed that the fluorescence lifetime of TRP was highly sensitive to changes in molecular conformation and the environment. In in vitro cell experiments, we successfully utilized the fluorescence lifetime of TRP to distinguish tumor cells from healthy cells, track the therapeutic effect of the tumor immunotherapy drug 1-MT for HeLa cells, and monitor cells in response to carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced cell apoptosis. These results reveal that the two-photon excitation autofluorescence lifetime of TRP could be a sensitive natural probe of cell metabolism in living cells.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Comparison of midterm efficacy of Kirschner wires and elastic intramedullary nails after closed reduction of Judet type 3 radial neck fractures in children: a multicenter study.

Objective: The objective of this study was to compare the midterm efficacy of Kirschner wires and elastic intramedullary nails after the closed reduction treatment of Judet 3 radial neck fractures in children. Methods: This was a retrospective multicenter study of patients diagnosed with Judet type 3 radial neck fractures who underwent closed reduction and internal fixation at four tertiary hospitals from January 2019 to December 2021. Gender, age, fracture type, operation time, follow-up time, x-ray results and complications were collected. The recovery of elbow joint between the two internal fixation methods, elbow motion and complications at the last follow-up were compared. Results: The average operation time of EIN group was statistical significantly increased compared with KW group. There were no significant differences in MEPS score and ROM 3 months after surgery between the two groups, but the ROR Angle of EIN group was statistical significantly increased compared with KW group 3 months after surgery. There were no significant differences in MEPS score, ROM and ROR at the last follow-up. The incidence of complications in EIN group was significantly lower than that in KW group. Conclusion: The use of elastic intramedullary nails fixation or Kirschner wires fixation in the treatment of radial neck fractures in children can both achieve satisfactory fracture reduction and healing. Compared with elastic intramedullary nails, the operation time of Kirschner wires fixation is shorter, and the internal fixation does not need to be removed under anesthesia again, but the complication rate is higher.

Facile synthesis of hydroxylated triazine-based magnetic microporous organic network for ultrahigh adsorption of phenylurea herbicides: An experimental and density-functional theory study.

Microporous organic networks (MONs) are highly porous materials that are particularly useful in analytical chemistry. However, the use of these materials is often limited by the functional groups available on their surface. Here, we described the polymerization of a sea urchin-like structure material at ambient temperature, that was functionalized with hydroxyl, carboxyl, and triazine groups and denoted as OH-COOH-MON-TEPT. A substantial proportion of OH-COOH-MON-TEPT was intricately decorated EDA-Fe3O4, creating a well-designed configuration (EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC) for superior adsorption of the target analytes phenylurea herbicides (PUHs) via magnetic solid-phase extraction (MSPE). The proposed method showed remarkably low limits of detection ranging from 0.03 to 0.22 ng·L-1. Experimental investigations and theoretical analyses unveiled the adsorption mode between EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC and PUHs. These findings establish a robust foundation for potential applications of EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC in the analysis of various polar contaminants.

Accurate piecewise centroid calculation algorithm for wavefront measurement in adaptive optics.

Adaptive optics using direct wavefront sensing (direct AO) is widely used in two-photon microscopy to correct sample-induced aberrations and restore diffraction-limited performance at high speeds. In general, the direct AO method employs a Sharked-Hartman wavefront sensor (SHWS) to directly measure the aberrations through a spot array. However, the signal-to-noise ratio (SNR) of spots in SHWS varies significantly within deep tissues, presenting challenges for accurately locating spot centroids over a large SNR range, particularly under extremely low SNR conditions. To address this issue, we propose a piecewise centroid calculation algorithm called GCP, which integrates three optimal algorithms for accurate spot centroid calculations under high-, medium-, and low-SNR conditions. Simulations and experiments demonstrate that the GCP can accurately measure aberrations over a large SNR range and exhibits robustness under extremely low-SNR conditions. Importantly, GCP improves the AO working depth by 150 µm compared to the conventional algorithm.

Adult-onset combined oxidative phosphorylation deficiency type 14 manifests as epileptic status: a new phenotype and literature review.

BACKGROUND: Combined oxidative phosphorylation deficiency (COXPD) is a severe disorder with early onset and autosomal recessive inheritance, and has been divided into 51 types (COXPD1-COXPD51). COXPD14 is caused by a mutation in the FARS2 gene, which encodes mitochondrial phenylalanyl-tRNA synthetase (mt-PheRS), an enzyme that transfers phenylalanine to its cognate tRNA in mitochondria. Since the first case was reported in 2012, an increasing number of FARS2 variations have been subsequently identified, which present three main phenotypic manifestations: early onset epileptic encephalopathy, hereditary spastic paraplegia, and juvenile-onset epilepsy. To our knowledge, no adult cases have been reported in the literature. METHODS: We report in detail a case of genetically confirmed COXPD14 and review the relevant literature. RESULTS: Approximately 58 subjects with disease-causing variants of FARS2 have been reported, including 31 cases of early onset epileptic encephalopathy, 16 cases of hereditary spastic paraplegia, 3 cases of juvenile-onset epilepsy, and 8 cases of unknown phenotype. We report a case of autosomal recessive COXPD14 in an adult with status epilepticus as the only manifestation with a good prognosis, which is different from that in neonatal or infant patients reported in the literature. c.467C > T (p.T156M) has been previously reported, while c.119_120del (p.E40Vfs*87) is novel, and, both mutations are pathogenic. CONCLUSIONS: This case of autosomal recessive COXPD14 in an adult only presented as status epilepticus, which is different from the patients reported previously. Our study expands the mutation spectrum of FARS2, and we tended to define the phenotypes based on the clinical manifestation rather than the age of onset.

Highly sensitive analysis of trace germanium derived from the efficient electrosynthesis and spectral introduction of GeH4 on foam electrode.

BACKGROUND: The electrochemical hydride generation technology, which uses electrolysis instead of chemical reagents to generate reducing species to achieve gaseous transformation and sample introduction of the tested elements, has received widespread attention in the field of atomic spectroscopy due to its simple, economical, and green characteristics. However, limited by the effective area of the electrode, the introduction efficiency and spectral signal of most elements (e.g., germanium) in practical applications are lower than traditional chemical hydride generation. RESULTS: In this paper, an efficient electrochemical hydride generation (EHG) method based on metal foam electrode for µg L-1 level germanium was constructed. Systematic electrochemical and spectral tests showed that the low charge transfer resistance and the high electrochemical activity of nickel-based foam electrodes jointly promoted the efficient electroreduction of Ge(IV). Besides, the porous network structure of the metal foam material improves the contact probability of reactants while reducing the gas-evolution effect caused by bubble accumulation. Interestingly, adequate reaction sites are crucial for the conversion of germanium, but large foam electrodes are not always compatible with analytical performance. After coupling atomic fluorescence spectroscopy, this new electrolysis method has been proven to be suitable for efficient conversion and quantitative detection of Ge over a wide concentration range (5-150 µg L-1). SIGNIFICANCE: Our proposal to improve the electrosynthesis efficiency of germanane (GeH4) by using metal foam electrode is extremely effective for the detection of trace or ultra-trace germanium. The exploration of electrode material, structure, and especially effective area will also provide ideas for the establishment of highly sensitive analysis methods in the future.

Recent advance of ATP citrate lyase inhibitors for the treatment of cancer and related diseases.

ATP citrate lyase (ACLY), a strategic metabolic enzyme that catalyzes the glycolytic to lipidic metabolism, has gained increasing attention as an attractive therapeutic target for hyperlipidemia, cancers and other human diseases. Despite of continual research efforts, targeting ACLY has been very challenging. In this field, most reported ACLY inhibitors are "substrate-like" analogues, which occupied with the same active pockets. Besides, some ACLY inhibitors have been disclosed through biochemical screening or high throughput virtual screening. In this review, we briefly summarized the cancer-related functions and the recent advance of ACLY inhibitors with a particular focus on the SAR studies and their modes of action. We hope to provide a timely and updated overview of ACLY and the discovery of new ACLY inhibitors.

Outcomes of Robotic Versus Laparoscopic Pancreatoduodenectomy Following Learning Curves of Surgeons: A Multicenter Study on 2255 Patients.

OBJECTIVE: This study aimed to compare robotic pancreatoduodenectomy (RPD) with laparoscopic pancreatoduodenectomy (LPD) in operative and oncologic outcomes. BACKGROUND: Previous studies comparing RPD with LPD have only been carried out in small, single-center studies with variable quality. METHODS: Consecutive patients from nine centers in China who underwent RPD or LPD between 2015 and 2022 were included. A 1:1 propensity score matching (PSM) was used to minimize bias. RESULTS: Of the 2,255 patients, 1158 underwent RPD and 1097 underwent LPD. Following PSM, 1006 patients were enrolled in each group. The RPD group had significantly shorter operative time (270.0 vs. 305.0 minutes, P<0.001), lower intraoperative blood transfusion rate (5.9% vs. 12.0%, P<0.001), lower conversion rate (3.8% vs. 6.7%, P=0.004), and higher vascular reconstruction rate (7.9% vs. 5.6%, P=0.040) than the LPD group. There were no significant differences in estimated blood loss, postoperative length of stay, perioperative complications, and 90-day mortality. Patients who underwent vascular reconstruction had similar outcomes between the two groups, although they had significantly lower estimated blood loss (300.0 vs. 360.0 mL; P=0.021) in the RPD group. Subgroup analysis on pancreatic ductal adenocarcinoma (PDAC) found no significant differences between the two groups in median recurrence-free survival (14.3 vs. 15.3 mo, P=0.573) and overall survival (24.1 vs. 23.7 mo, P=0.710). CONCLUSIONS: In experienced hands, both RPD and LPD are safe and feasible procedures with similar surgical outcomes. RPD had the perioperative advantage over LPD especially in vascular reconstruction. For PDAC patients, RPD resulted in similar oncological and survival outcomes as LPD.

Accessory navicular in children.

Accessory navicular (AN) is a developmental variation of the secondary ossification center of the navicular tuberosity. Ten percent of patients with AN will have pain symptoms that affect walking and life. As the AN changes the position of the posterior tibial tendon insertion, children with AN often have posterior tibial tendon function insufficiency and flexible flat foot. Surgical treatment is often required after failure of conservative treatment. This article reviewed the etiology, clinical manifestations, complications, and treatment methods of AN.