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Wan-Yi Rao,1,&ast; Fang Xu,1,&ast; Shao-Bing Dai,1 Zhong Mei,2 Xiao-Ping Chen,1 Chang-Cheng Lv,1 Chun-Lei Liu,1 Warwick Ngan Kee,1 Xin-Zhong Chen1 1Department of Anesthesia, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Anesthesiology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin-Zhong Chen, Department of Anesthesia, Women’s Hospital, Zhejiang University School of Medicine, No. 1 Bachelor’s Road, Hangzhou, 310000, People’s Republic of China, Email chenxinz@zju.edu.cnPurpose: Catheter-based techniques such as combined spinal-epidural (CSE) anesthesia which are sometimes indicated for obstetric anesthesia have a complex mechanism of action. The application of the dural puncture epidural (DPE) anesthesia for cesarean section (CS) has not been well investigated. The present study compared the relatively novel DPE technique with epidural (EA) and CSE anesthesia.Patients and Methods: We randomly assigned 150 parturients who underwent elective CS to receive DPE, EA or CSE anesthesia. The primary outcome was the onset of sensory anesthesia to the T5 dermatome assessed using the Cox proportional hazards model. Secondary outcomes included median time to sensory block, quality of block, patient and surgeon satisfaction, APGAR scores and other side effects.Results: For DPE anesthesia versus EA anesthesia, the onset of anesthesia was faster (hazard ratio 2.47 [95% CI 1.56 to 3.90], adjusted P < 0.001) and the median time to surgical level was shorter (16 [IQR 14– 18] min versus 19 [15.5– 21] min, adjusted P < 0.001); the incidence of intraoperative pain was lower (7/48 versus 17/47, adjusted P = 0.046) and the median patient satisfaction score was higher (9 [IQR 9– 10] versus 8 [8– 9.5], adjusted P = 0.004). In the CSE group, the onset of anesthesia was faster than in the other two but the incidence of hypotension was higher (P < 0.001) and the phenylephrine requirement was greater (P < 0.001).Conclusion: DPE anesthesia had a faster onset and better quality of block than EA anesthesia and provided less influence to maternal hemodynamic parameters than CSE anesthesia for CS. These results suggest that the dural puncture plays a significant role in enhancing the effectiveness of epidural top-ups during CSE anesthesia and indicates enlightenment that contributes to the satisfaction of anesthetic effect in DPE technique labor analgesia transferred to CS.Keywords: anesthesia, dural puncture epidural, anesthesia, epidural, cesarean section

Bin-Yong Liang,1,&ast; Jin Gu,2,&ast; Min Xiong,3 Er-Lei Zhang,1 Zun-Yi Zhang,1 Wan-Yee Lau,4 Shao-Fa Wang,5 Yan Guan,1 Xiao-Ping Chen,1 Zhi-Yong Huang1 1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Faculty of Medicine, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, People’s Republic of China; 5Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Yong Huang, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, People’s Republic of China, Tel +86-27-83665392, Fax +86-27-83663432, Email huangzy@tjh.tjmu.edu.cnBackground: Hepatocellular carcinoma (HCC) is frequently associated with cirrhosis. The present study investigated the impact of histological severity of cirrhosis on surgical outcomes for HCC and further developed novel nomograms to predict postoperative recurrence and survival.Methods: A total of 1524 consecutive patients undergoing curative hepatectomy for HCC between 1999 and 2015 were retrospectively studied. Cirrhotic severity was histologically staged according to the Laennec staging system. Short- and long-term outcomes were investigated. Recurrence-free survival (RFS) and overall survival (OS) predictive nomograms were constructed based on the results of multivariate analysis. The predictive accuracy of the nomograms was measured by the concordance index (C-index) and calibration.Results: Patients in the severe cirrhosis group had significantly higher morbidity and mortality rates than patients in the no, mild, and moderate cirrhosis groups. The 5-year RFS and OS rates were 36.8% and 64.5%, respectively, in the no cirrhosis group, compared to 34.8% and 60.4% in the mild cirrhosis group, 17.3% and 43.4% in the moderate cirrhosis group, and 6.1% and 20.1% in the severe cirrhosis group. Long-term survival outcomes were significantly worse as cirrhotic severity was increased. The C-index was 0.727 for the RFS nomogram and 0.746 for the OS nomogram. Calibration curves showed good agreement between actual observations and nomogram predictions. The 2 nomograms had a superior discriminatory ability to predict RFS and OS compared to other staging systems.Conclusion: Histological severity of cirrhosis significantly affected surgical outcomes in HCC patients undergoing curative hepatectomy. The novel nomograms, including histological severity of cirrhosis, showed an accurate prediction of postoperative recurrence and survival.Keywords: hepatocellular carcinoma, Laennec staging system, prognosis, nomogram, hepatectomy

Jie Hu,1,2 Xin-juan Su,2 Hui-Ling Si,2 Rui-Xiang Song,3 Fang Zhang,3 Xiang-Jun Qiu,3 Xing-Peng Chen2 1Department of Anesthesiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 2Department of Anesthesiology, Luoyang Central Hospital, Luoyang, Henan Province, 471003, People’s Republic of China; 3School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, People’s Republic of ChinaCorrespondence: Xiang-Jun QiuSchool of Basic Medicine, Henan University of Science and Technology, Luoyang, 471023, People’s Republic of ChinaEmail lyxiangjun@126.comXing-Peng ChenLuoyang Central Hospital, Luoyang, Henan Province, 471003, People’s Republic of ChinaEmail lycxp2020@126.comBackground: An efficient, fast and sensitive ultra high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for simultaneous determination of celecoxib (CEL), dezocine (DEZ) and dexmedetomidine (DEX) in beagle plasma were established.Methods: The beagle dogs plasmawas precipitated by acetonitrile. The column was Acquity UPLC BEH C18 column and the mobile phase was acetonitrile-formic acid with gradient mode, and the flow rate was set at 0.4 mL/min. Under the positive ion mode, CEL, DEZ, DEX and Midazolam (internal standard, IS) were monitored by multiple reaction monitoring (MRM) as the following mass transition pairs: m/z 381.10→ 282.10 for CEL, m/z 246.20→ 147.00 for DEZ, m/z 201.10→ 94.90 for DEX, and m/z 326.10→ 291.10 for IS.Results: This UPLC-MS/MS method had good linearity for CEL, DEZ and DEX. The RSDs of inter-day and intra-day precision were the values of 0.31– 7.66% and 0.11– 9.63%, respectively; the RE values were from − 6.05% to 10.98%. The extraction recovery was more than 79%, and the matrix effect was around 100%. The RSDs of stability were less than 8.96%. All of them met the acceptance standard of biological analysis method recommended by FDA.Conclusion: This UPLC-MS/MS method is an effective tool for the simultaneous determination of CEL, DEX and DEX, and has been successfully applied to the study of pharmacokinetics in beagle dogs.Keywords: celecoxib, dezocine, dexmedetomidine, UPLC-MS/MS, pharmacokinetics, beagles

Xiao-ping Chen, Yi Li, Yu Zhang, Gao-wei Li Department of Oncology, Beibei District Hospital of Traditional Chinese Medicine, Chongqing, People’s Republic of ChinaCorrespondence: Yi LiBeibei District Hospital of Traditional Chinese Medicine, No. 380, General Road, Beibei District, Chongqing 400711, People’s Republic of ChinaTel/fax +86 23 68863618Email yili2a@sina.comBackground: Liver cancer is a major health problem facing mankind. Currently, the focus of research is to improve the treatment of liver cancer using a variety of treatment options such as providing chemotherapy drugs through nanocarriers.Purpose: The aim of this study was to prepare a curcumin-loaded (PLGA/TPGS) NPs delivery system by the emulsification-solvent evaporation method in order to achieve synergistic antitumor activity against liver cancer.Methods: Curcumin-loaded (PLGA/TPGS) NPs were prepared by the emulsification and solvent evaporation method. The physical and chemical characteristics of NPs such as size, morphology, and release profiles were discussed. In vitro and in vivo studies were carried out to evaluate its anti-tumor activity in target cells.Results: Curcumin-loaded (PLGA/TPGS) NPs could be successfully internalized by HepG2 cells and play a synergistic role in inhibiting the growth of hepatocellular carcinoma cells. They exhibited high target organ accumulation, superior antitumor efficiency, and lower toxicity in vivo.Conclusion: The present study indicates that the curcumin-loaded (PLGA/TPGS) NPs provide a promising platform for the treatment of liver cancer.Keywords: curcumin, PLGA, TPGS, nanoparticles, liver cancer

Bingbing Liu,1 Xueping Chen,1 Yang Li,1 Hui Liu,2 Shasha Guo,2 Ping Yu3 1Nursing Department, Qianjiang College, Hangzhou Normal University, Hangzhou, China; 2Medicine Department, Hangzhou Normal University, Hangzhou, China; 3School of Computing and Information Technology, Faculty of Engineering and Information Sciences, University of Wollongong, Wollongong, NSW, Australia Background: Dementia adds burden to society. As it is not curable, physical exercise activities are optimal to improve the physical strength and quality-of-life of people with dementia. Aim: Design, implementation, and examination of a set of passive finger exercises and their effects on improving grip strength and activities of daily living (ADL) for older people with dementia. Methods: Forty older people with dementia were recruited and randomly allocated into an experimental group and a control group, each with 20 people. The control group received routine nursing care. In addition to this, the experimental group received 25-minutes of passive finger exercises every day for 12 weeks. The health outcomes measured were grip strength and ADL, before and after the intervention. Grip strength was assessed by electrical hand muscle dynamometer. ADL were assessed with Barthel index. Results: Although there was no effect on grip strength, passive finger exercises led to significant improvements in urinary control, defecation function, and overall ADL in comparison with the control group. Implications for practice: Passive finger exercises can be integrated into physical exercise programs for older people with dementia to improve their urinary control, defecation function, and ADL. Keywords: physical exercise, passive finger exercise, grip strength, urinary control, defecation, activities of daily living, ADL, dementia

Objective: To assess the medical community's awareness and practice regarding delirium in the intensive care unit (ICU).Methods: One hundred and ten predesigned questionnaires were distributed to ICU practitioners in the affiliated hospitals of Zhejiang University.Results: A total of 105 valid questionnaires were collected. Totally, 55.3% of the clinicians considered that delirium was common in the ICU. Delirium was believed to be a significant or serious problem by 70.5% of respondents, and under-diagnosis was acknowledged by 56.2% of the respondents. The incidence of ICU delirium is even more under-estimated by the pediatric doctors compared with their counterparts in adult ICU (P less than 0.05). Primary disease of the brain (agreed by 82.1% of the respondents) was believed to be the most common risk factor for delirium. None of the ICU professionals screened delirium or used a specific tool for delirium assessment routinely. The vast majority (92.4%) of respondents had little knowledge on the diagnosis and the standard treatment of delirium.Conclusions: Although delirium is considered as a serious problem by a majority of the surveyed ICU professionals, it is still under-recognized in routine critical care practice. Data from this survey show a disconnection between the perceived significance of delirium and the current practices of monitoring and treatment in ICU in China. [ABSTRACT FROM AUTHOR]

In a Chinese myoclonus-dystonia syndrome (MDS) family presented with a phenotype including a typical MDS, cervical dystonia, and writer's cramp, genetic analyses revealed a novel 662 + 1insG heterozygous mutation in exon 5 in the epsilon-sarcoglycan (SGCE) gene, leading to a frameshift with a down stream stop codon. Low SGCE mRNA levels were detected in the mutation carriers by real-time PCR, suggesting that the nonsense mutation might interference with the stability of SGCE mRNA. This is the first report on Chinese with a SGCE mutation leading to MDS. Our data support the fact that same mutation of SGCE gene can lead to a varied phenotype, even in the same family. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Aspirin Decreases Systemic Exposure to Clopidogrel Through Modulation of P-Glycoprotein but Does Not Alter Its Antithrombotic Activity" by J. Oh and colleagues in a 2014 issue.

Liver metastases are commonly detected in the advanced stages of various malignant tumors, representing a significant clinical challenge. Throughout the process of liver metastases formation, immune cells play a pivotal role, particularly in the pre-metastatic and metastatic niches within the liver. Immune cells establish extensive and intricate interactions with tumor cells and other components in the liver, collectively promoting and sustaining the growth of liver metastases. Despite the limited efficacy of existing therapeutic modalities against some advanced liver metastases, novel immune-based treatment approaches are continuously being explored and validated. Building on the systematic elucidation of the immunosuppressive characteristics of liver metastases, we explored the potential of novel immunotherapies applicable to patients with liver metastases from multiple dimensions., Competing Interests: Declarations Ethical approval Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

A retention time (RT)-independent strategy for nontargeted screening of pesticide residues in herbs was exploited using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF MS). The core of this strategy is a fingerprint database coupled with a data-independent acquisition (DIA) scan mode of all ion fragmentation (AIF). In the fingerprint database, a total of 150 pesticides with quasimolecular ions and fragment ions at five-level collision energies were collected as qualified ions for screening. During the data acquisition, the AIF scan was performed via real unbiased full-spectrum MS/MS acquisition. Six herb matrices spiked with 30 banned pesticides were used to evaluate the applicability of the strategy in real samples. The use of the narrow ion mass extraction window (10 mDa) and the narrow RT window (0.1 min) enabled the effective extraction of spectra from noisy backgrounds and the discovery of suspected pesticides via similarity matching of filtered qualified ions. On average, more than 11/30 of pesticides at 1 ng mL -1 and more than 23/30 of pesticides at 10 ng mL -1 or lower could be screened out in each matrix using at least two qualified ions. In addition, the AIF mode exhibited superior anti-interference capability compared to data-dependent acquisition (DDA) and sequential window acquisition of all theoretical mass spectra (SWATH), as determined by comparing the limits of screening (LOSs) of 30 banned pesticides spiked into Isatidis Folium . Finally, the developed strategy was applied to screen pesticide residues in extracts of Ganoderma and Foeniculi Fructus . Phorate-sulfone and phorate-sulfoxide were found in Ganoderma , as well as terbufos-sulfone and terbufos-sulfoxide were found in Foeniculi Fructus . In conclusion, the developed RT-independent strategy based on a fingerprint database and AIF acquisition with LC-QTOF MS seems to be one of the most efficient tools for the analysis of nontargeted pesticide residues in complicated matrices.

Pepper (Capsicum spp.) is an important fruit vegetable worldwide, and it is a rich dietary source of minerals for human being. Yet, the spatio-temporal distribution of pepper fruit mineral composition and the factors influencing such variations at global scale remain unknown. A global meta-analysis of 140 publications providing 649, 562, 690, 811 datapoints was conducted to quantify and evaluate the nutritional quality, comprising potassium (K), magnesium (Mg), iron (Fe) and zinc (Zn), of pepper fruits and its influencing variables. The analysis showed that the global average of K, Mg, Fe and Zn content in pepper fruits was 20-25 g kg -1 , 1-1.5 g kg -1 , 80-100 mg kg -1 , and 20-40 mg kg -1 , respectively. There had been a downward trend in pepper fruit nutritional quality over the last decade, especially for Fe and Zn. And, the concentration of all these four nutrients were at lower levels in less developed regions, especially in Africa. Our results showed that the vegetable "green pepper" contains more K, Mg, Fe and Zn than the "hot pepper" used as spice. The concentration of K, Mg, Fe and Zn were increased with fruit yield but that of Fe and Zn were decreased with increase in single fruit weight. Nutritional quality was optimal at mean annual temperature of 10 ℃ - 20 ℃, and was adversely affected when mean annual precipitation was < 500 mm. Pepper fruits produced at pH 6.5-7.5 had higher fruit K concentration while acidic soils (pH<6.5) favored higher Fe and Zn concentrations. The higher soil organic matter (SOM) generally improved the nutritional quality of the pepper. Our results suggest that systematic selection of superior varieties and soil amelioration (adjusting pH and SOM) of the soil-crop system are needed to achieve higher nutritional quality of pepper fruit., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Although multidisciplinary clinics improve outcomes in chronic limb-threatening ischemia (CLTI), their role in addressing socioeconomic disparities is unknown. Our institution treats patients with CLTI at both traditional general vascular clinics and a multidisciplinary Limb Preservation Program (LPP). The LPP is in a minority community, providing expedited care at a single facility by a consistent team. We compared outcomes within the LPP with our institution's traditional clinics and explored patients' perspectives on barriers to care to evaluate if the LPP might address them., Methods: All patients undergoing index revascularization for CLTI from 2014 to 2023 at our institution were stratified by clinic type (LPP or traditional). We collected clinical and socioeconomic variables, including Area Deprivation Index (ADI). Patient characteristics were compared using χ 2 , Student t, or Mood median tests. Outcomes were compared using log-rank and multivariable Cox analysis. We also conducted semi-structured interviews to understand patient-perceived barriers., Results: From 2014 to 2023, 983 limbs from 871 patients were revascularized; 19.5% of limbs were treated within the LPP. Compared with traditional clinic patients, more LPP patients were non-White (43.75% vs 27.43%; P < .0001), diabetic (82.29% vs 61.19%; P < .0001), dialysis-dependent (29.17% vs 13.40%; P < .0001), had ADI in the most deprived decile (29.38% vs 19.54%; P = .0061), resided closer to clinic (median 6.73 vs 28.84 miles; P = .0120), and had worse Wound, Ischemia, and foot Infection (WIfI) stage (P < .001). There were no differences in freedom from death, major adverse limb event (MALE), or patency loss. Within the most deprived subgroup (ADI >90), traditional clinic patients had earlier patency loss (P = .0108) compared with LPP patients. Multivariable analysis of the entire cohort demonstrated that increasing age, heart failure, dialysis, chronic obstructive pulmonary disease, and increasing WIfI stage were independently associated with earlier death, and male sex was associated with earlier MALE. Ten traditional clinic patients were interviewed via convenience sampling. Emerging themes included difficulty understanding their disease, high visit frequency, transportation barriers, distrust of the health care system, and patient-physician racial discordance., Conclusions: LPP patients had worse comorbidities and socioeconomic deprivation yet had similar outcomes to healthier, less deprived non-LPP patients. The multidisciplinary clinic's structure addresses several patient-perceived barriers. Its proximity to disadvantaged patients and ability to conduct multiple appointments at a single visit may address transportation and visit frequency barriers, and the consistent team may facilitate patient education and improve trust. Including these elements in a multidisciplinary clinic and locating it in an area of need may mitigate some negative impacts of socioeconomic deprivation on CLTI outcomes., Competing Interests: Disclosures None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Applying conductive hydrogels in electronic skin, health monitoring, and wearable devices has aroused great research interest. Yet, it remains a significant challenge to prepare conductive hydrogels simultaneously with superior mechanical, self-recovery, and conductivity performance. Herein, a dual ionically cross-linked double network (DN) hydrogel is fabricated based on K + and Fe 3+ ion cross-linked κ-carrageenan (κ-CG) and Fe 3+ ion cross-linked poly(sodium acrylate-co-acrylamide) P(AANa-co-AM). Benefiting from the abundance of hydrogen bonds and metal coordination bonds, the conductive hydrogel has excellent mechanical properties (fracture strain up to 1420 %, fracture stress up to 2.30 MPa, and toughness up to 20.63 MJ/m 3 ) and good self-recovery performance (the recovery rate of the toughness can reach 85 % after waiting for 1 h). Meanwhile, due to the introduction of dual metal ions of K + and Fe 3+ , the ionic conductivity of conductive hydrogel is up to 1.42 S/m. Furthermore, the hydrogel strain sensor has good sensitivity with a gauge factor (GF) of 2.41 (0-100 %). It can be a wearable sensor that monitors different human motions, such as sit-ups. This work offers a new synergistic strategy for designing a hydrogel strain sensor with high mechanical, self-recovery, and conductive properties., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Transition metal oxides (TMOs) are important anode materials in sodium-ion batteries (SIBs) due to their high theoretical capacities, abundant resources, and cost-effectiveness. However, issues such as the low conductivity and large volume variation of TMO bulk materials during the cycling process result in poor electrochemical performance. Nanosizing and compositing with carbon materials are two effective strategies to overcome these issues. In this study, spherical MnFe 2 O 4 @xC nanocomposites composed of MnFe 2 O 4 inner cores and tunable carbon shell thicknesses were successfully prepared and utilized as anode materials for SIBs. It was found that the property of the carbon shell plays a crucial role in tuning the electrochemical performance of MnFe 2 O 4 @xC nanocomposites and an appropriate carbon shell thickness (content) leads to the optimal battery performance. Thus, compared to MnFe 2 O 4 @1C and MnFe 2 O 4 @8C, MnFe 2 O 4 @4C nanocomposite exhibits optimal electrochemical performance by releasing a reversible specific capacity of around 308 mAh·g -1 at 0.1 A·g -1 with 93% capacity retention after 100 cycles, 250 mAh·g -1 at 1.0 A g -1 with 73% capacity retention after 300 cycles in a half cell, and around 111 mAh·g -1 at 1.0 C when coupled with a Na 3 V 2 (PO 4 ) 3 (NVP) cathode in a full SIB cell.

Objectives: Both age and CYP2C19 genotypes affect voriconazole plasma concentration; the interaction of age and CYP2C19 genotypes on voriconazole plasma concentration remains unknown. This study aims to investigate the combined effects of age and CYP2C19 genotypes on voriconazole plasma concentration in Chinese patients., Methods: A total of 480 patients who received voriconazole treatment were recruited. CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) polymorphisms were genotyped. Patients were divided into the young and the elderly groups by age of 60 years old. Influence of CYP2C19 genotype on steady-state trough concentration (C ss-min ) in overall patients and in age subgroups was analyzed., Results: Voriconazole C ss-min correlated positively with age, and mean voriconazole C ss-min was significantly higher in the elderly group ( P  < 0.001). CYP2C19 poor metabolizers showed significantly increased mean voriconazole C ss-min in the young but not the elderly group. The percentage of patients with subtherapeutic voriconazole C ss-min (<1.0 mg/l) was higher in the young group and that of supratherapeutic voriconazole C ss-min (>5.5 mg/l) was higher in the elderly patients. When the average C ss-min in the CYP2C19 normal metabolizer genotype was regarded as a reference, CYP2C19 genotypes showed greater impact on voriconazole C ss-min in the young group, while the influence of age on voriconazole C ss-min exceeded CYP2C19 genotypes in the elderly., Conclusion: CYP2C19 genotypes affects voriconazole exposure is age dependent. Influence of CYP2C19 poor metabolizer genotype on increased voriconazoleexposure is prominent in the young, while age is a more important determinant factor for increased voriconazole exposure in the elderly patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: According to the theory of traditional Chinese medicine (TCM), the spleen and stomach are the basis of acquired nature and the source of qi and blood biochemistry. After surgery and chemotherapy, patients with colorectal cancer often develop spleen and stomach qi deficiency syndrome, leading to decreased immune function. Buzhong Yiqi decoction, a classic TCM prescription, has the effect of tonifying middle-jiao and invigorating qi, boosting Yang, and suppressing immune-related inflammation. Moreover, it is widely used in the treatment of spleen and stomach qi deficiency syndrome., Aim: To investigate the effect of Buzhong Yiqi decoction on spleen and stomach qi deficiency in patients with colorectal cancer., Methods: One hundred patients with colorectal cancer who underwent preoperative chemotherapy and laparoscopy at The First TCM Hospital of Changde from January 2022 to October 2023 were retrospectively analyzed. The patients were divided equally into control and observation groups. Both groups underwent conventional rehabilitation surgery, and the observation group was supplemented with Buzhong Yiqi decoction. SPSS 26.0 was used for statistical analyses. The χ 2 test was used for univariate analysis; independent sample t -tests were used in all cases., Results: No significant differences were observed preoperatively in the general characteristics of the two groups. Fourteen days post-surgery, the abdominal distension, emaciation, loose stool, loss of appetite, and vomiting scores were significantly lower in the observation group than in the control group ( P < 0.05). Immune function and interleukin (IL)-10 levels in the observation group were significantly higher than those of the control group, whereas IL-6, tumor necrosis factor-α, and C-reactive protein levels, tumor biological indexes, and adverse reactions in the observation group were significantly lower than those of the control group ( P < 0.05). One month after surgery, the patients' quality of life in the observation group was significantly higher than that of the patients in the control group ( P < 0.05)., Conclusion: Buzhong Yiqi decoction can regulate inflammatory responses and metabolic processes by enhancing immune function, thereby promoting overall immune nutrition and restoring the body's balance., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To establish the diagnostic accuracy of RASSF1A (Ras association domain family 1 isoform) methylation using bronchial aspirates as an auxiliary method for diagnosing lung cancer through a systematic review and meta-analysis., Methods: Studies published prior to October 30, 2022, were retrieved from the Embase, PubMed, Web of Science, and Wan Fang databases using the keywords "lung cancer", "RASSF1A", "methylation", and "bronchial aspirates". A fixed or random effect model was used to calculate the combined sensitivity, specificity, positive likelihood ratios (LR), negative LR, diagnostic odds ratio (DOR), along with the respective 95% confidence intervals (CIs) and the area under the curve (AUC) with Q index. The threshold effect was defined by using the Spearman correlation coefficient, and the Deeks funnel plot was generated to evaluate publication bias., Results: Among the 12 trials that met the inclusion criteria, a total of 2388 participants were involved. The pooled results for the diagnosis of lung cancer were as follows, when compared to the pathological diagnosis: sensitivity of 0.47 (95% CI: 0.45-0.50), specificity of 0.96 (95% CI: 0.95-0.97), positive LR of 12.18 (95% CI: 8.96-16.55), negative LR of 0.56 (95% CI: 0.52-0.61), DOR of 24.05 (95% CI: 17.29-33.47), and AUC of 0.78 (Q index = 0.72), respectively. The sensitivity of the RASSF1A methylation assay was relatively low in a detailed subgroup analysis, fluctuating between 0.39 and 0.90, indicating a limitation in its diagnostic value for lung cancer. The RASSF1A methylation assay, on the other hand, demonstrated excellent specificity, suggesting a high exclusion value. Of note, the diagnostic sensitivity, specificity, DOR, and AUC for small cell lung cancer were 0.90 (0.84-0.94), 0.95 (0.94-0.97), 249.5 (103.94-598.8), and 0.98, respectively, showing that RASSF1A methylation was a promising biomarker for diagnosing small cell lung cancer with both high diagnostic and exclusion value. Furthermore, RASSF1A methylation using bronchial washings and bronchial aspirates showed a high AUC of 0.998 and 0.93, respectively, indicating excellent diagnostic performance., Conclusions: The methylation of RASSF1A in bronchial aspirates demonstrated a high level of diagnostic accuracy and has the potential to be a valuable supplementary diagnostic method, especially for identifying small cell lung cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Clarifying the matching degree and the trade-offs and synergies between supply and demand of ecosystem services is of significance for scientific division of management zoning and sustainable urban development. We calculated the supply and demand of ecosystem services at the sub-district (town) scale of Taiyuan based on multi-source data, explored the coldspots and hotspots area of the supply-demand ratio and the trade-offs and synergies of six ecosystem services using the Getis-Ord Gi * tool and correlation analysis, and proposed strategies based on the regional characteristics of natural-resource and socio-economy. Results showed the distribution of the supply and demand of ecosystem services had a spatial heterogeneity. In terms of supply, the area with high supply of carbon storage, air purification, thermal environment regulation and recreation service were located in the east and west parts, that of soil conservation in the west and water yield in the south part. In terms of demand, the demand distribution of carbon storage, thermal environment regulation, water yield and recreation service were characterized by high in the central and east-south area, and low in the periphery, and high demand of air purification in south and north parts, soil conservation in west part. There were substantial mismatches between the demand and supply of ecosystem services. The risk levels of the supply and demand of six ecosystem services showed a decreasing pattern from the Fenhe River to the eastern and western mountains. There were trade-offs between water yield and other five ecosystem services in their supply, while air purification and soil conservation had trade-offs with other four ecosystem services in demand. Based on the regional ecological management framework, we divided the study area into three primary zones and eight secondary zones, and proposed differentiated ecological management strategies to provide theoretical support for ecological zoning. The results could provide a basis for balancing the relationship of supply and demand of ecosystem services and promoting the sustainable development of the city.

Background: Juvenile hemochromatosis (JH) is an early-onset, rare autosomal recessive disorder of iron overload observed worldwide that leads to damage in multiple organs. Pathogenic mutations in the hemojuvelin ( HJV ) gene are the major cause of JH., Case Summary: A 34-year-old male Chinese patient presented with liver fibrosis, diabetes, hypogonadotropic hypogonadism, hypophysis hypothyroidism, and skin hyperpigmentation. Biochemical test revealed a markedly elevated serum ferritin level of 4329 μg/L and a transferrin saturation rate of 95.4%. Targeted exome sequencing and Sanger sequencing revealed that the proband had a novel mutation c.863G>A (p.R288Q) in the HJV gene which was transmitted from his father, and two known mutations, c.18G>C (p.Q6H) and c.962&#95;963delGCinsAA (p.C321*) in cis, which were inherited from his mother. The p.R288W mutation was previously reported to be pathogenic for hemochromatosis, which strongly supported the pathogenicity of p.R288Q reported for the first time in this case. After 72 wk of intensive phlebotomy therapy, the patient achieved a reduction in serum ferritin to 160.5 μg/L. The patient's clinical symptoms demonstrated a notable improvement., Conclusion: This study highlights the importance of screening for hemochromatosis in patients with diabetes and hypogonadotropic hypogonadism. It also suggests that long-term active phlebotomy could efficiently improve the prognosis in severe JH., Competing Interests: Conflict-of-interest statement: The authors who have taken part in this study declare that they do not have anything to disclose regarding funding or conflicts of interest with respect to this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: This study aimed to evaluate the effects of varying auxiliaries on tooth movement and stress distribution when maxillary central incisors were torqued 1° with a clear aligner through finite element analysis., Methods: Three-dimensional finite element models, including maxillary alveolar bone, periodontal ligament, dentition, and clear aligner, were constructed. According to the auxiliaries designed on the maxillary central incisor, 5 models were created: (1) without auxiliaries (control model), (2) with the power ridge, (3) with the semi-ellipsoid attachment, (4) with the horizontal rectangular attachment, and (5) with the horizontal cylinder attachment. The tooth movement and periodontal ligament stress distribution after a palatal root torque of 1° were analyzed for each of the 5 models., Results: With 1° torque predicted, the maxillary central incisor without auxiliaries showed a tendency of labial tipping, mesial tipping, and intrusion. The rotation center moved occlusally in the power ridge model. The labiolingual inclination variation increased in the semi-ellipsoid attachment model but decreased in the power ridge model. The maxillary central incisor is twisted in the distal direction in the power ridge model. The maxillary central incisor of the horizontal rectangular attachment and the horizontal cylinder attachment model behaved similarly to the control model. Periodontal stresses were concentrated in the cervical and apical areas. The maximum von Mises stresses were 11.6, 12.4, 3.81, 1.14, and 11.0 kPa in the 5 models. The semi-ellipsoid attachment model exhibited a more uniform stress distribution than the other models., Conclusions: Semi-ellipsoid attachment performed better efficacy on labiolingual inclination, and power ridge performed better efficacy on root control. However, a distal twist of maxillary incisors could be generated by the power ridge., (Copyright © 2024 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Humans are exposed to various chemical elements that have been associated with the development and progression of diseases such as coronary artery disease (CAD). Unlike previous research, we employed a multi-element approach to investigate CAD patients and those with comorbid conditions such as diabetes (CAD-DM2), high blood pressure (CAD-HBP), or high blood lipids (CAD-HBL). Plasma concentrations of 21 elements, including lithium (Li), boron (B), aluminum (Al), calcium (Ca), titanium (Ti), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), strontium (Sr), cadmium (Cd), tin (Sn), stibium (Sb), barium (Ba), and lead (Pb), were measured in CAD patients (n = 201) and healthy subjects (n = 110) using inductively coupled plasma-mass spectrometry (ICP-MS). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were utilized to analyze the ionomic profiles. Spearman correlation analysis was employed to identify the interaction patterns among individual elements. We found that levels of Ba, Li, Ni, Zn and Pb were elevated in the CAD group compared to the healthy group, while Sb, Ca, Cu, Ti, Fe, and Se were lower. Furthermore, the CAD-DM2 group exhibited higher levels of Ni and Cd, while the CAD-HBP group showed lower levels of Co and Mn. In the CAD-HBL group, Ti was increased, whereas Ba, Cr, Cu, Co, Mn, and Ni were reduced. In conclusion, ionomic profiles can be utilized to differentiate CAD patients from healthy individuals, potentially providing insights for future treatment or dietary interventions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Schistosoma infection is one of the major causes of liver fibrosis. Emerging roles of hepatic progenitor cells (HPCs) in the pathogenesis of liver fibrosis have been identified. Nevertheless, the precise mechanism underlying the role of HPCs in liver fibrosis in schistosomiasis remains unclear. This study examined how autophagy in HPCs affects schistosomiasis-induced liver fibrosis by modulating exosomal miRNAs. The activation of HPCs was verified by immunohistochemistry (IHC) and immunofluorescence (IF) staining in fibrotic liver from patients and mice with Schistosoma japonicum infection. By coculturing HPCs with hepatic stellate cells (HSCs) and assessing the autophagy level in HPCs by proteomic analysis and in vitro phenotypic assays, we found that impaired autophagy degradation in these activated HPCs was mediated by lysosomal dysfunction. Blocking autophagy by the autophagy inhibitor chloroquine (CQ) significantly diminished liver fibrosis and granuloma formation in S. japonicum-infected mice. HPC-secreted extracellular vehicles (EVs) were further isolated and studied by miRNA sequencing. miR-1306-3p, miR-493-3p, and miR-34a-5p were identified, and their distribution into EVs was inhibited due to impaired autophagy in HPCs, which contributed to suppressing HSC activation. In conclusion, we showed that the altered autophagy process upon HPC activation may prevent liver fibrosis by modulating exosomal miRNA release and inhibiting HSC activation in schistosomiasis. Targeting the autophagy degradation process may be a therapeutic strategy for liver fibrosis during Schistosoma infection., (© 2024. Higher Education Press.)

Two tryptophan compound classes 5- and 6-borono PEGylated boronotryptophan derivatives have been prepared for assessing their aqueous solubility as formulation of injections for boron neutron capture therapy (BNCT). The PEGylation has improved their aqueous solubility thereby increasing their test concentration in 1 mM without suffering from toxicity. In-vitro uptake assay of PEGylated 5- and 6-boronotryptophan showed that the B-10 concentration can reach 15-50 ppm in U87 cell whereas the uptake in LN229 cell varies. Shorter PEG compound 6-boronotryptophanPEG200[ 18 F] was obtained in 1.7 % radiochemical yield and the PET-derived radioradioactivity percentage in 18 % was taken up by U87 tumor at the limb of xenograft mouse. As high as tumor to normal uptake ratio in 170 (T/N) was obtained while an inferior radioactivity uptake of 3 % and T/N of 8 was observed in LN229 xenografted mouse., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Robotic surgery is increasingly utilized and common in general surgery training programs. This study sought to better understand the factors that influence resident operative autonomy in robotic surgery. We hypothesized that resident seniority, surgeon work experience, surgeon robotic-assisted surgery (RAS) case volume, and procedure type influence general surgery residents' opportunities for autonomy in RAS as measured by percentage of resident individual console time (ICT)., Methods: General surgery resident ICT data for robotic cholecystectomy (RC), inguinal hernia (RIH), and ventral hernia (RVH) operations performed on the dual-console Da Vinci surgical robotic system between July 2019 and June 2021 were extracted. Cases with postgraduate year (PGY) 2-5 residents participating as a console surgeon were included. A sequential explanatory mixed-methods approach was undertaken to explore the ICT results and we conducted secondary qualitative interviews with surgeons. Descriptive statistics and thematic analysis were applied., Results: Resident ICT data from 420 robotic cases (IH 200, RC 121, and VH 99) performed by 20 junior residents (PGY2-3), 18 senior residents (PGY4-5), and 9 attending surgeons were extracted. The average ICT per case was 26.8 % for junior residents and 42.4 % for senior residents. Compared to early-career surgeons, surgeons with over 10 years' work experience gave less ICT to junior (18.2 % vs. 32.0 %) and senior residents (33.9 % vs. 56.6 %) respectively. Surgeons' RAS case volume had no correlation with resident ICT (r = 0.003, p = 0.0003). On average, residents had the most ICT in RC (45.8 %), followed by RIH (36.7 %) and RVH (28.6 %). Interviews with surgeons revealed two potential reasons for these resident ICT patterns: 1) Surgeon assessment of resident training year/experience influenced decisions to grant ICT; 2) Surgeons' perceived operative time pressure inversely affected resident ICT., Conclusions: This study suggests resident ICT/autonomy in RC, RIH, and RVH are influenced by resident seniority level, surgeon work experience, and procedure type, but not related to surgeon RAS case volume. Design and implementation of an effective robotic training program must consider the external pressures at conflict with increased resident operative autonomy and seek to mitigate them., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Theresa Wang reports equipment, drugs, or supplies was provided by Intuitive Foundation. Michael P. Meara reports a relationship with Intuitive Surgical Inc that includes: consulting or advisory., (© 2024 The Authors.)

The aims of our study were to examine whether initial or subsequent adiposity status had a greater effect on hypertension. We collected data in 1992 and again in 2007 from the same group of 597 individuals in the middle age. The subjects were classified into four groups: individuals with a normal body mass index (BMI) in 1992 and 2007 were in Group I; those with a normal BMI in 1992, but became overweight or obese in 2007 were in Group II; those who were overweight or obese in 1992, but had a normal BMI in 2007 were in Group III; and those who were overweight or obese in 1992 and 2007 were in Group IV. Their demographic data were recorded. The relationship between adiposity status and hypertension was analyzed using logistic regression model. The cumulative incidence of hypertension was 35.5%, 56.3%, 50.0%, and 65.1% for Group I to IV, respectively. Compared with Group I, after adjusted factors, the hazard ratio (HR) was 1.80 for Group II (P = .001), 1.40 for Group III (P = .150), and 2.31 for Group IV (P < .001). Adiposity status in 2007 could predict hypertension (OR = 2.5, P < .001), as opposed to the initial adiposity status (P = .148). Subsequently adiposity status could have major effects on hypertension. Our society is very short of public health resources, particularly in developing countries, we should pay more attention to current adiposity status and encourage middle-aged people to lose weight., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Objective: Recombinase-aided polymerase chain reaction (RAP) is a sensitive, single-tube, two-stage nucleic acid amplification method. This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Acinetobacter baumannii (AB) in the bloodstream based on recombinant human mannan-binding lectin protein (M1 protein)-conjugated magnetic bead (M1 bead) enrichment of pathogens combined with RAP., Methods: Recombinant plasmids were used to evaluate the assay sensitivity. Common blood influenza bacteria were used for the specific detection. Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR (M-RAP) and quantitative PCR (qPCR) assays. Kappa analysis was used to evaluate the consistency between the two assays., Results: The M-RAP method had sensitivity rates of 1, 10, and 1 copies/μL for the detection of SA, PA, and AB plasmids, respectively, without cross-reaction to other bacterial species. The M-RAP assay obtained results for < 10 CFU/mL pathogens in the blood within 4 h, with higher sensitivity than qPCR. M-RAP and qPCR for SA, PA, and AB yielded Kappa values of 0.839, 0.815, and 0.856, respectively ( P < 0.05)., Conclusion: An M-RAP assay for SA, PA, and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances., Results: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-β promoted cytostasis and partial epithelial-mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-β activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFβ-Smad signaling induced growth inhibition and partial EMT, whereas TGFβ-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-β was mutually restricted in LPCs. Mechanistically, we found that TGF-β activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFβ-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-β-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-β-induced cytostasis and partial EMT., Conclusion: These results suggested that TGF-β downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-β under fibrotic conditions and maintain partial EMT and progenitor phenotypes.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data., Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF., Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram., Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram., Trial Registration: Clinicaltrials.gov Identifier: NCT04076631., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-22-410/coif). The authors have no conflicts of interest to declare., (2024 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Objective: Operative coaching (OC) may facilitate improvement of surgery residents' competencies by optimizing learning and teaching. We investigated how residents' operative skills and prospective entrustment (PE) progress throughout the chief year in our OC program, how OC is perceived by participants, and how OC may facilitate learning and teaching., Design, Setting, and Participants: This is a mixed-methods study conducted within the Ohio State University Wexner Medical Center General Surgery residency. Validated performance evaluations with procedural-specific skill, general skill (GS), step-specific guidance required (SSG) (an autonomy measure), and PE measures completed by chiefs, faculty coaches, and attending surgeons from 7/2018 to 6/2022 were reviewed. We also interviewed OC participants to understand their experience. Descriptive statistical and qualitative content analysis were applied., Results: 441 evaluations from 147 OC cases completed by 22 chiefs, 5 faculty coaches, and 24 attendings were included. Overall, resident GS (p = 0.036), SSG (p = 0.023), and PE (p = 0.002) significantly improved throughout the year. PE significantly correlated (all p < 0.0001) with SSG (r = 0.73), followed by procedural-specific skill (r = 0.59), then GS (r = 0.57). On average, chiefs underestimated their surgical skills while attendings overestimated autonomy they permitted to residents. Chiefs, coaches, and attendings reached consensus on chiefs' PE upon graduation. Five graduated chiefs and 5 attendings were interviewed. Chiefs described OC as effective in improving their self-regulated learning and particularly valued 3 OC elements: neutral authentic feedback, third-party real-time observation, and actionable feedback. Attendings noted OC promoted their engagement in skills assessment and teaching., Conclusions: Our findings suggest chief residents' skills, autonomy, and PE progress steadily along their OC journey. Despite differences in residents', coaches', and attendings' perceptions of skill, measures of autonomy reliably correlate with entrustment. OC promotes resident learning, faculty teaching, and assessment of resident skills, autonomy, and PE in the OR., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear whether laparoscopic hepatectomy (LH) for hepatolithiasis confers better clinical benefit and lower hospital costs than open hepatectomy (OH). This study aim to evaluate the clinical and economic value of LH versus OH., Methods: Patients undergoing OH or LH for primary hepatolithiasis at Yijishan Hospital of Wannan Medical College between 2015 and 2022 were divided into OH group and LH group. Propensity score matching (PSM) was used to balance the baseline data. Deviation-based cost modelling and weighted average median cost (WAMC) were used to assess and compare the economic value., Results: A total of 853 patients were identified. After exclusions, 403 patients with primary hepatolithiasis underwent anatomical hepatectomy (OH n=143; LH n=260). PSM resulted in 2 groups of 100 patients each. Although LH required a longer median operation duration compared with OH (285.0 versus 240.0 min, respectively, P<0.001), LH patients had fewer wound infections, fewer pre-discharge overall complications (26 versus 43%, respectively, P=0.009), and shorter median postoperative hospital stays (8.0 versus 12.0 days, respectively, P<0.001). No differences were found in blood loss, major complications, stone clearance, and mortality between the two matched groups. However, the median overall hospital cost of LH was significantly higher than that of OH (CNY¥52,196.1 versus 45,349.5, respectively, P=0.007). Although LH patients had shorter median postoperative hospital stays and fewer complications than OH patients, the WAMC was still higher for the LH group than for the OH group with an increase of CNY¥9,755.2 per patient undergoing LH., Conclusion: The overall clinical benefit of LH for hepatolithiasis is comparable or even superior to that of OH, but with an economic disadvantage. There is a need to effectively reduce the hospital costs of LH and the gap between costs and diagnosis-related group reimbursement to promote its adoption., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells., Methods: In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059). The binding capacity of GenSci059 to CD47 was evaluated using flow cytometry and surface plasmon resonance (SPR) methods, the inhibitory effect of GenSci059 on the CD47-SIRPα interaction was evaluated through competitive ELISA assays. The anti-tumor activity of GenSci059 was assessed using in vitro macrophage models and in vivo patient-derived xenograft (PDX) models. To evaluate the safety profile of GenSci059, binding assays were conducted using blood cells. Additionally, we investigated the underlying mechanisms contributing to the weaker binding of GenSci059 to erythrocytes. Finally, toxicity studies were performed in non-human primates to assess the potential risks associated with GenSci059., Results: GenSci059 displayed strong binding to CD47 in both human and monkey, and effectively inhibited the CD47-SIRPα interaction. With doses ranging from 5 to 20 mg/kg, GenSci059 demonstrated potent inhibition of the growth of subcutaneous tumor with the inhibition rates ranged from 30.3% to complete regression. Combination of GenSci059 with 2.5 mg/kg Rituximab at a dose of 2.5 mg/kg showed enhanced tumor inhibition compared to monotherapy, exhibiting synergistic effects. GenSci059 exhibited minimal binding to hRBCs compared to Hu5F9-G4. The binding of GenSci059 to CD47 depended on the cyclization of N-terminal pyroglutamic acid and the spatial conformation of CD47, but was not affected by its glycosylation modifications. A maximum tolerated dose (MTD) of 450 mg/kg was observed for GenSci059, and no significant adverse effects were observed in repeated dosages up to 10 + 300 mg/kg, indicating a favorable safety profile., Conclusion: GenSci059 selectively binds to CD47, effectively blocks the CD47/SIRPα axis signaling pathway and enhances the phagocytosis effects of macrophages toward tumor cells. This monoclonal antibody demonstrates potent antitumor activity and exhibits a favorable safety profile, positioning it as a promising and effective therapeutic option for cancer., (© 2024. The Author(s).)

Thermal ablative techniques such as radiofrequency and microwave ablation are minimally invasive and cost-effective approaches that are currently being adopted as alternatives to surgical resection for primary and metastatic liver malignancies. However, they are considered to be relatively contraindicated for tumors in high-risk locations due to technical difficulties and a perceived increased risk of perioperative complications. Several techniques, including artificial ascites, non-touch multibipolar ablation, and laparoscopically assisted ablation, can be used to improve the outcomes of ablation for high-risk tumors. This review aims to provide a comprehensive summary of the techniques currently used to improve thermal ablation outcomes for high-risk liver tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Cytarabine (Ara-C) is widely used in the induction chemotherapy for acute myeloid leukemia (AML). Association between LncRNA GAS5 genetic polymorphism and the recovery of hematopoietic function after Ara-C-based chemotherapy is observed. This study aimed to identify whether intervention of GAS5 expression and GAS5 genotype affect Ara-C-induced inhibition of hematopoietic stem cells (HSCs) differentiation. In this study, cord blood-derived CD34 + cells were cultured in vitro, and a cell model of myelosuppression was established by treatment of CD34 + cells with Ara-C. The effect of GAS5 overexpression, Ara-C treatment, and GAS5 rs55829688 genotype on the hematopoietic colony-forming ability of CD34 + cells was assessed using methylcellulose-based colony forming unit assay. GAS5 overexpression slowed down the proliferation of cord blood-derived CD34 + cells significantly (p < 0.05) and decreased their ability to form hematopoietic colonies in vitro. Ara-C significantly reduced the hematopoietic colony-forming ability of CD34 + cells in vitro (p < 0.0001), and overexpressing GAS5 further decreased the number of hematopoietic colonies. GAS5 expression was higher in CD34 + cells than in CD34 - cells, and positively correlated with GATA1 mRNA expression in CD34 + cells in vitro culture. However, GAS5 genotype had no effect on the total number of hematopoietic colonies formed from cord blood-derived CD34 + cells. In conclusion, our study highlights that GAS5 inhibited the in vitro proliferation and reduced the hematopoietic colony-forming ability of cord blood-derived CD34 + cells, with the most pronounced effect observed on CFU-GEMM formation. GAS5 also enhanced the inhibitory effect of Ara-C on the in vitro hematopoietic ability of CD34 + HSCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5 th edition of the World Health Organization Classification of Tumours of the Digestive System., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Objective: To compare the effects of ampulla-guided realignment and conventional gallbladder triangle anatomy in difficult laparoscopic cholecystectomy (DLC)., Methods: From June 2021 to August 2022, data from 100 patients undergoing DLC at Nanjing Hospital of Traditional Chinese Medicine were analyzed retrospectively. Patients were divided into two groups: the experimental group (LC with the ampulla-guided realignment) and the control group (conventional LC with triangular gallbladder anatomy), with 50 patients per group. The intraoperative blood loss, operation time, postoperative drainage tube indwelling time, hospitalization time, bile duct injury rate, operation conversion rate, and incidence of postoperative complications were recorded and compared between the two groups. The pain response and daily activities of the patients in the two groups were evaluated 48 h after the operation., Results: The amount of intraoperative blood loss, postoperative drainage tube indwelling time, hospital stay, operation conversion rate, pain degree at 24 and 48 h after operation, bile duct injury incidence, and total postoperative complication rate were shorter or lower in the experimental group than those in the control group (p < 0.05). The Barthel index scores of both groups were higher 48 h after the operation than before the operation, and the experimental group was higher than the control group (p < 0.05)., Conclusion: The ampulla-guided alignment in DLC surgery was more beneficial in promoting postoperative recovery, reducing postoperative pain response, reducing the incidence of postoperative complications, and reducing bile duct injury., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Rater-based assessment and objective assessment play an important role in evaluating residents' clinical competencies. We hypothesize that a cumulative sum (CUSUM) chart of operative time is a complement to the assessment of chief general surgery residents' competencies with ACGME Milestones, aiding residency programs' determination of graduating residents' practice readiness., Study Design: We extracted ACGME Milestone evaluations of performance of operations and procedures (POP) and 3 objective metrics (operative time, case type, and case complexity) from 3 procedures (cholecystectomy, colectomy, and inguinal hernia) performed by 3 cohorts of residents (N = 15) during their PGY4-5. CUSUM charts were computed for each resident on each procedure type. A learning plateau was defined as at least 4 cases consistently locating around the centerline (target performance) at the end of a CUSUM chart with minimal deviations (range 0 to 1)., Results: All residents reached the ACGME graduation targets for the overall POP by the end of chief year. A total of 2,446 cases were included (cholecystectomy N = 1234, colectomy N = 507, and inguinal hernia N = 705), and 3 CUSUM chart patterns emerged: skewed distribution, bimodal distribution, and peaks and valleys distribution. Analysis of CUSUM charts revealed surgery residents' development processes in the operating room towards a learning plateau vary, and only 46.7% residents reach a learning plateau in all 3 procedures upon graduation., Conclusions: CUSUM charts of operative time complement the ACGME Milestones evaluations. The use of both may enable residency programs to holistically determine graduating residents' practice readiness and provide recommendations for their upcoming career/practice transition., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Ventricular septal rupture (VSR) is a serious complication occurring after myocardial infarction (MI). Cardiogenic shock (CS) is a common complication of VSR and an important factor affecting its prognosis. CS can occur in either an immediate or delayed manner after VSR; however, studies on the risk factors associated with immediate or delayed CS are scarce., Methods: We retrospectively studied patients diagnosed with VSR after MI and admitted to the West China Hospital between September 2009 and August 2023. Demographic data, medical history, physical examination results, electrocardiograms, and echocardiographic and hematological data were extracted from electronic medical records or archived records. CS was defined as hypotension (<90 mmHg) and/or the requirement for catecholamines, pulmonary congestion, and signs of end-organ failure. The CS onset time was defined as the time at which catecholamines were initiated., Results: A total of 88 patients with VSR after MI, including 49 males (55.7%), were enrolled. The average age was 70.2 years. Of these patients, 32 (36.4%) who already had CS at the time of VSR discovery were defined as immediate CS, and 28 (31.8%) who developed CS within 2 weeks after VSR discovery were defined as delayed CS. A smaller left ventricular end-diastolic diameter (LVEDD) and VSR discovered after admission were independent risk factors for immediate CS. Elevated heart rate and higher levels of creatine kinase-MB isoenzyme on admission were independent risk factors for delayed CS in patients without immediate CS after VSR., Conclusions: The occurrence of CS in patients with VSR after MI has an evident time course. Thus, an early identification of patients at risk of immediate or delayed CS and optimization of treatment procedures may help improve the prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Wang, Zhang, Xiao, Liu, Xu, Chen, Wei and Peng.)

Objective: Robotic-assisted surgery is an increasing part of general surgery training, but resident autonomy on the robotic platform can be hard to quantify. Robotic console time (RCT), the percentage of time the resident controls the console, may be an appropriate measure of resident operative autonomy. This study aims to characterize the correlation between objective resident RCT and subjectively scored operative autonomy., Methods: Using a validated resident performance evaluation instrument, we collected resident operative autonomy ratings from residents and attendings performing robotic cholecystectomy (RC) and robotic inguinal hernia repair (IH) at a university-based general surgery program between 9/2020-6/2021. We then extracted RCT data from the Intuitive surgical system. Descriptive statistics, t-tests and ANOVA were performed., Results: A total of 31 robotic operations (13 RC, 18 IH) performed by 4 attending surgeons and 8 residents (4 junior, 4 senior) were matched and included. 83.9% of cases were scored by both attending and resident. The average RCT per case was 35.6%(95% CI 13.0%,58.3%) for junior residents (PGY 2-3) and 59.7%(CI 51.1%,68.3%) for senior residents (PGY 4-5). The mean autonomy evaluated by residents was 3.29(CI 2.85,3.73) out of a maximum score of 5, while the mean autonomy evaluated by attendings was 4.12(CI 3.68,4.55). RCT significantly correlated with subjective evaluations of resident autonomy (r=0.61, p=0.0003). RCT also moderately correlated with resident training level (r=0.5306, p<0.0001). Neither attending robotic experience nor operation type significantly correlated with RCT or autonomy evaluation scores., Conclusions: Our study suggests that resident console time is a valid surrogate for resident operative autonomy in robotic cholecystectomy and inguinal hernia repair. RCT may be a valuable measure in objective assessment of residents' operative autonomy and training efficiency. Future investigation into how RCT correlates with subjective and objective autonomy metrics such as verbal guidance or distinguishing critical operative steps is needed to validate the study findings further., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

In this work, a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry (LC-MS) method was developed for metabolite profiling of the glutathione anabolic pathway (GAP) in cancer tissues and cells. The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate (DMMIC) was used to label the amino group of metabolites, and a reductant of dithiothreitol (DTT) was employed to stabilize the thiol group. By combining DMMIC derivatization with LC-MS, it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples, which had good linearity ( R 2 = 0.9981-0.9999), precision (interday precision of 1.6%-19.0% and intraday precision of 1.4%-19.8%) and accuracy (83.4%-115.7%). Moreover, the recovery assessments in tissues (82.5%-107.3%) and in cells (98.1%-118.9%) with GSH- 13 C2, 15 N, and Cys- 15 N demonstrated the reliability of the method in detecting tissues and cells. Following a methodological evaluation, the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma (ESCC) and the effect of p -hydroxycinnamaldehyde (CMSP) on the GAP in KYSE-150 esophageal cancer cells. The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes, which can contribute to research on drugs and diseases., (© 2023 The Author(s).)

Background: Waist circumference can be used as an anthropometric measure to assess central obesity and is easier and more convenient than the waist-to-hip ratio in identifying the risk of obesity and medical problems. Most studies showing an association between obesity and infertility in women have used BMI to measure obesity. Our goal was to examine any potential association between waist circumference and infertility., Methods: This cross-sectional study, which formed part of the National Health and Nutrition Examination Survey (NHANES), comprised women ages 18 to 45 between 2017 and 2020. Participants without waist circumference data or information on infertility were removed from the study. The independent relationship between waist circumference and infertility was investigated using weighted binary logistic regression and subgroup analysis., Results: We investigated 1509 participants and discovered that the prevalence of infertility rose as the WC trisection rose. (tertile 1, 7.55%; tertile 2, 10.56%; tertile 3, 15.28%; trend < 0.001). Multivariate logistic regression showed that after total adjustment, higher WC levels were associated with an increased likelihood of infertility in women (OR1.02; 95% CI 1.01-1.03), and There was a 2% rise in the incidence of infertility for every unit (cm) increased WC. Subgroup analysis and interaction tests showed no significant dependence of the effects of marital status, diabetes, hypertension, and high cholesterol on the association between WC and infertility ( p for all interaction tests > 0.05). The inflection point of the positive non-linear relationship between WC and infertility was 116.6 cm., Conclusion: Excessive waist circumference assessment may increase the probability of infertility, and more attention should be paid to the management of waist circumference should be given more attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yin, Zhou, Lu, Chen, Liu, Lu, Han and Wu.)