Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

ObjectiveTo elucidate the epidemiological characteristics, evolution of the pathogen spectrum, and spatial distribution patterns of other infectious diarrheal diseases (excluding cholera, typhoid fever, paratyphoid fever, and bacillary dysentery) in Yangpu District of Shanghai from 2005 to 2024, thereby providing a scientific basis for the formulation of targeted prevention and control strategies. MethodsInformation on other infectious diarrhea cases with a current address in Yangpu District of Shanghai, and onset dates from January 1, 2005 to December 31, 2024, was extracted from the Chinese Center for Disease Control and Prevention Information System. Data on cases, including gender, age, occupation, and pathogen testing results, were collected. Descriptive epidemiological methods were employed to analyze the temporal, spatial, and demographic distribution of reported incidence rates and the epidemiological characteristics of pathogens for other infectious diarrheal diseases in Yangpu District from 2005 to 2024. Spatial autocorrelation analyses of reported incidence rates for viral and bacterial diarrhea were conducted using Moran’s Index (Moran’s I）. Local spatial autocorrelation analyses were performed using local indicators of spatial association (LISA), with a first-order Queen contiguity spatial weight matrix, and significance was tested via 999 random permutations. Time-series and radar chart analyses were used to examine the temporal patterns of other infectious diarrhea cases caused by major pathogens. ResultsFrom 2005 to 2024, a total of 5 211 cases of other infectious diarrhea were reported in Yangpu District. The cases were predominantly males (2 714 cases, accounting for 52.08%) and children under 5 years of age (1 639 cases, accounting for 31.45%). The primary occupational groups were scattered children (1 433 cases, accounting for 27.50%) and retired personnel (1 403 cases, accounting for 26.92%). The annual average reported incidence rate was 20.36/100 000, showing an overall fluctuating trend with peaks around 2009 and 2024. Peak incidence occurred in summer and autumn (July‒September), with the highest reported incidence rate observed in summer (June‒August) (7.31/100 000). Children under 5 years of age (116.00/100 000) and adults aged 60 and older (21.39/100 000) were the top two age groups in terms of reported incidence. Global spatial autocorrelation analyses showed that the reported incidence rates of viral diarrhea across the sub-districts in Yangpu District in 2020 exhibited a significant positive spatial correlation (Moran’s I =0.30, P=0.016). The spatial autocorrelation of reported incidence rates of viral diarrhea in each sub-district for the periods 2008‒2019 and 2021‒2024 was not statistically significant (all P>0.05). Local spatial autocorrelation analyses of viral diarrhea incidence in 2020 revealed that Xinjiangwancheng Sub-district exhibited a low‑low clustering trend (local Moran’s I =0.49, P=0.018), while Dinghai Road Sub-district exhibited a high‑high clustering trend (local Moran’s I =1.33, P=0.024). The global spatial autocorrelation of reported incidence rates of bacterial diarrhea across the sub-districts of Yangpu District from 2005 to 2024 was not statistically significant (all P>0.05). Among the 5 211 cases, 4 049 had definitive pathogen test results. Bacterial diarrhea accounted for a relatively high proportion (55.52%, 2 248/4 049). The pathogens with the highest proportions were rotavirus (32.33%, 1 309/4 049), Vibrio spp. (31.69%, 1 283/4 049), Salmonella spp. (19.63%, 795/4 049), and norovirus (9.16%, 371/4 049). The radar chart showed that diarrhea cases caused by norovirus had no obvious seasonality, rotavirus cases were mainly concentrated in winter, and cases caused by Salmonella spp. and Vibrio spp. were mainly concentrated in summer and autumn. Among cases under 20 years of age, rotavirus accounted for a relatively high proportion, especially in children under 5 years of age. Among cases aged 20 years and older, Vibrio spp. and Salmonella spp. accounted for relatively high proportions. ConclusionFrom 2005 to 2024, other infectious diarrhea in Yangpu District of Shanghai was most prevalent in summer and autumn. Children under 5 years of age and adults aged 60 years and older were high-risk groups. In 2020, Dinghai Road Sub-district was a high-risk area for viral diarrhea. Rotavirus, Vibrio spp., Salmonella spp., and norovirus were the dominant pathogens. Prevention and control efforts for other infectious diarrhea should be strengthened among key populations (e.g., children under 5 years of age and adults aged 60 years and older) and in high-risk areas such as Dinghai Road Sub-district. During summer and autumn, priority should be given to the prevention and control of bacterial diarrhea caused by Salmonella spp. and Vibrio spp., especially among individuals aged 20 years and older (particularly those aged 60 and above). During winter, priority should be given to the prevention and control of diarrhea caused by rotavirus infection among individuals under 20 years of age, particularly children under 5 years of age.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To investigate the complications, along with their diagnosis and management, that follow local excision for rectal cancer after neoadjuvant therapy.Methods:The clinical data of 53 patients with rectal cancer who underwent local resection after neoadjuvant treatment in Peking Union Medical College Hospital from January, 2010 to December, 2024 were retrospectively collected for this descriptive case series study. Indications for local resection were: (1) age ≥ 18 years; (2) American Society of Anesthesiologists (ASA) classification I-III; (3) pathologically confirmed rectal adenocarcinoma; (4) distance from the lower edge of the tumor to the anal edge of less than 8 cm; and (5) use of preoperative neoadjuvant therapy. Contraindications of local resection were: (1) multiple primary colorectal cancer and (2) intestinal obstruction, intestinal perforation, or and gastrointestinal bleeding that required emergency surgery. There were 36 males and 17 females, and the median age was 62 (26-85) years. After neoadjuvant therapy, the median distance from the tumor to the anal margin was 4.5 (range, 2.2-6.9) cm. The main outcome measures included: surgical details, pathological findings, postoperative complications, anorectal function, and oncological outcomes (recurrence and survival).Results:Surgical methods included transanal endoscopic microsurgery (TEM) in 47 cases, transanal minimally invasive surgery (TAMIS) in 3 cases, and traditional transanal local resection in 3 cases. Of the 53 patients, 29 (54.7%) had pathological complete response (pCR), namely pT0 stage; 8 cases were pT1, 15 cases were pT2, and 1 case was pT3. Twenty-four cases (45.3%) had 33 complications. Clavien-Dindo grade I-II accounted for 97.0% (32/33), including 14 cases (26.4%) of wound dehiscence. Low anterior resection syndrome (LARS) occurred in 7 cases (13.2%), including 5 minor cases and 2 major cases. Postoperative fever occurred in 7 cases (13.2%); urinary retention occurred in 3 cases (5.7%); and diarrhea occurred in 1 case (1.9%). Clavien Dindo grade III was observed in only 3.0% (1/33) of patients, which was a rectovaginal fistula. Among the 14 patients with wound dehiscence, 7 cases only suffered anal pain and were cured after symptomatic analgesic treatment. Five cases suffered anal pain with hematochezia but improved after treatment with essential diet, hemostasis, intravenous antibiotics, pain relief, and sitz bath. Two cases of secondary perianal infection were treated with intravenous antibiotics, local drainage, parenteral nutrition support, and symptomatic treatment, and the wounds healed within 2 months. One patient with rectovaginal fistula underwent transverse colostomy. After six months, the fistula healed and stoma reversal was performed. Seven patients with LARS received anal lifting exercise and defecation reflex training, and anal function recovered to the preoperative level after 1 year. Other complications improved after symptomatic treatment, pain relief, or catheter replacement. The median follow-up time was 60 months. Local recurrence occurred in 4 patients (7.5%) and distant metastasis occurred in 12 patients (22.6%). Seven patients (13.2%) died. The 5-year disease-free survival rate was 75.5%, and the 5-year overall survival rate was 86.8%.Conclusions:Local excision for rectal cancer following neoadjuvant therapy has a high incidence of complications, mainly wound-related, due to the decline of rectal wound healing ability after radiotherapy. However, most of the complications were relieved after symptomatic treatment, and the risk was controllable.

Objective:To investigate the complications, along with their diagnosis and management, that follow local excision for rectal cancer after neoadjuvant therapy.Methods:The clinical data of 53 patients with rectal cancer who underwent local resection after neoadjuvant treatment in Peking Union Medical College Hospital from January, 2010 to December, 2024 were retrospectively collected for this descriptive case series study. Indications for local resection were: (1) age ≥ 18 years; (2) American Society of Anesthesiologists (ASA) classification I-III; (3) pathologically confirmed rectal adenocarcinoma; (4) distance from the lower edge of the tumor to the anal edge of less than 8 cm; and (5) use of preoperative neoadjuvant therapy. Contraindications of local resection were: (1) multiple primary colorectal cancer and (2) intestinal obstruction, intestinal perforation, or and gastrointestinal bleeding that required emergency surgery. There were 36 males and 17 females, and the median age was 62 (26-85) years. After neoadjuvant therapy, the median distance from the tumor to the anal margin was 4.5 (range, 2.2-6.9) cm. The main outcome measures included: surgical details, pathological findings, postoperative complications, anorectal function, and oncological outcomes (recurrence and survival).Results:Surgical methods included transanal endoscopic microsurgery (TEM) in 47 cases, transanal minimally invasive surgery (TAMIS) in 3 cases, and traditional transanal local resection in 3 cases. Of the 53 patients, 29 (54.7%) had pathological complete response (pCR), namely pT0 stage; 8 cases were pT1, 15 cases were pT2, and 1 case was pT3. Twenty-four cases (45.3%) had 33 complications. Clavien-Dindo grade I-II accounted for 97.0% (32/33), including 14 cases (26.4%) of wound dehiscence. Low anterior resection syndrome (LARS) occurred in 7 cases (13.2%), including 5 minor cases and 2 major cases. Postoperative fever occurred in 7 cases (13.2%); urinary retention occurred in 3 cases (5.7%); and diarrhea occurred in 1 case (1.9%). Clavien Dindo grade III was observed in only 3.0% (1/33) of patients, which was a rectovaginal fistula. Among the 14 patients with wound dehiscence, 7 cases only suffered anal pain and were cured after symptomatic analgesic treatment. Five cases suffered anal pain with hematochezia but improved after treatment with essential diet, hemostasis, intravenous antibiotics, pain relief, and sitz bath. Two cases of secondary perianal infection were treated with intravenous antibiotics, local drainage, parenteral nutrition support, and symptomatic treatment, and the wounds healed within 2 months. One patient with rectovaginal fistula underwent transverse colostomy. After six months, the fistula healed and stoma reversal was performed. Seven patients with LARS received anal lifting exercise and defecation reflex training, and anal function recovered to the preoperative level after 1 year. Other complications improved after symptomatic treatment, pain relief, or catheter replacement. The median follow-up time was 60 months. Local recurrence occurred in 4 patients (7.5%) and distant metastasis occurred in 12 patients (22.6%). Seven patients (13.2%) died. The 5-year disease-free survival rate was 75.5%, and the 5-year overall survival rate was 86.8%.Conclusions:Local excision for rectal cancer following neoadjuvant therapy has a high incidence of complications, mainly wound-related, due to the decline of rectal wound healing ability after radiotherapy. However, most of the complications were relieved after symptomatic treatment, and the risk was controllable.

[Objective] To investigate the clinical characteristics of patients who underwent multiple platelet transfusions (≥2 times) in Suzhou over the past 5 years (2017-2022), as to provide new insights for patients requiring long-term and substantial platelet transfusions. [Methods] A retrospective analysis was conducted on the type of diseases, volume and frequency of platelet transfusions in patients who were hospitalized in Suzhou and received multiple (≥2 times) apheresis platelet transfusions from August 2017 to August 2022. Compatibility transfusions were also performed for a subset of acute myeloid leukaemia (AML) patients who completed HLA antibody testing and genotyping. [Results] From 2017 to 2022, the clinical consumption of platelets in Suzhou has increased annually (P<0.001), and patients who received apheresis platelets were mainly concentrated in hematological diseases represented by hematopoietic or lymphoid tissue tumors, especially AML patients (48.81%, 1 188/2 434). The age group with the highest per capita number of transfusions among AML patients was predominantly 21-30 years old (25 times per person). After genotype-compatible transfusion for eligible AML patients, the CCI significantly increased (P<0.001). [Conclusion] For male AML patients aged 21-30 and 61-70 in Suzhou, conducting platelet antibody screening and genetic testing before platelet transfusion can improve the efficiency of transfusion, reduce the incidence of PTR, and save blood resources through personalized matching transfusions.

Natural compounds demonstrate unique therapeutic advantages for cancer treatment, primarily through direct tumor suppression or interference with the tumor microenvironment (TME). Glycyrrhizic acid (GL), a bioactive ingredient derived from the medicinal herb Glycyrrhiza uralensis Fisch., and its sapogenin glycyrrhetinic acid (GA), have been recognized for their ability to inhibit angiogenesis and remodel the TME. Consequently, the combination of GL with other therapeutic agents offers superior therapeutic benefits. Given GL's amphiphilic structure, self-assembly capability, and liver cancer targeting capacity, various GL-based nanoscale drug delivery systems have been developed. These GL-based nanosystems exhibit angiogenesis suppression and TME regulation properties, synergistically enhancing anti-cancer effects. This review summarizes recent advances in GL-based nanosystems, including polymer-drug micelles, drug-drug assembly nanoparticles (NPs), liposomes, and nanogels, for cancer treatment and tumor postoperative care, providing new insights into the anti-cancer potential of natural compounds. Additionally, the review discusses existing challenges and future perspectives for translating GL-based nanosystems from bench to bedside.
Animals ; Humans ; Antineoplastic Agents/therapeutic use* ; Glycyrrhizic Acid/therapeutic use* ; Liposomes/chemistry* ; Micelles ; Nanoparticles/chemistry* ; Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Nanoparticle Drug Delivery System/therapeutic use*

Aluminum is a light metal which is rich in the earth's crust and widely used. Recently, the adverse health effects of environmental and occupational aluminum exposure on human have attracted more and more attention. Aluminum exposure has toxic effects on the central nervous system and is believed to be closely related to the development and progression of Alzheimer's disease. The neurotoxic mechanism of aluminum is complex, especially the role of regulated cell death (RCD) in aluminum-induced neuronal death remains to be further studied. RCD refers to all modes of cell death regulated by multiple intracellular signal transduction pathways under physiological and pathological conditions, including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. This review summarized the morphological characteristics and mechanisms of each RCD mode in the process of aluminum-induced neuronal death, and discussed the relationship and transformation between different RCD modes, providing a new scientific basis for future studies on the treatment and intervention of neurotoxicity induced by aluminum exposure.

Red blood cell transfusion is an important method to treat anemia of prematurity. HoWever,there are 3 areas of controversy:(1)complications associated With red blood cell transfusion in preterm infants;(2)indications of red blood cell transfusion in preterm infants;(3)Which kind of red blood cell products is more suitable for preterm infants. In recent years,With the deepening of research,these problems above have made some neW progress and they have been applied to clinic. The implementation of these ideas and measures makes the premature infants With anemia get reasonable treatment,and reduces incidence of complications associated With red blood cell transfusion in preterm infants,and improves the prognosis of those sick preterm infants. NoW,the neW progress of red blood cell transfusion in preterm infants Was revieWed.