In recent years, the rising prevalence of obesity and its associated metabolic syndromes has emerged as a critical global public health concern. Sustained weight loss exceeding 10% of total body weight has been shown to ameliorate obesity-related comorbidities, including type 2 diabetes mellitus, hypertension, and hepatic steatosis. Recently, the potential of brown adipose tissue (BAT) to improve metabolism has garnered significant attention. However, evidence regarding weight loss therapies that promote BAT activation remains limited in preclinical models and is even scarcer in clinical studies, partly due to the paucity of appropriate BAT assessment techniques. This review aims to explore the potential impact of various weight loss therapies on BAT, with the goal of providing novel insights and strategies for the treatment of obesity.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To compare the efficacy of robot system-assisted versus freehand screw revision for ankylosing spondylitis (AS) with lower cervical fractures.Methods:A multicenter retrospective cohort study was conducted to analyze the clinical data of 57 patients with AS combined with lower cervical fractures admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University School of Medicine, Henan Provincial People's Hospital, Zhengzhou Orthopedic Hospital, and Qilu Hospital of Shandong University, including 46 males and 11 females, aged 38-77 years [(65.4±9.5)years]. Injury segments involved C 3 in 7 patients, C 4 in 13, C 5 in 25, C 6 in 10, and C 7 in 2. All the patients underwent revision surgery, among whom, 22 patients were treated with robot system-assisted cervical pedicle screw placement (robot nailing group, with 190 screws), and 35 with freehand cervical pedicle screw placement (freehand nailing group, with 300 screws). The operative duration, intraoperative bleeding volume, frequency of intraoperative fluoroscopy, incision length, and length of hospital stay of the two groups were compared; the time of single nscrew insertion, the number of single nail revisions, the distance between screws and the anterior cortex, the accuracy of screw placement of grade 0 and grade 0+1 were recorded in the two groups. The visual analogue scale (VAS), Japanese Orthopedic Society (JOA) score, neck dysfunction index (NDI), American Spine Injury Association (ASIA) classification before operation, at 3 days, 3 months after operation and at the last follow-up were compared between the two groups. The complication rate was also noted. Results:All the patients were followed up for 12-16 months [(14.3±2.1)months]. The operative duration, intraoperative bleeding volume, and frequency of intraoperative fluoroscopy were (186.4±12.9)minutes, (486.1±68.6)ml, and (3.4±1.3)times in the robot nailing group, which were shorter or less than (206.7±14.4)minutes, (660.3±45.2)ml, and (13.5±3.6)times in the freehand nailing group ( P<0.01). The incision length was (9.4±2.4)cm in the robot nailing group, longer than (5.6±1.2)cm in the freehand nailing group ( P<0.01), and the length of hospital stay was (3.7±0.4)days, shorter than (4.4±1.4)days in the freehand nailing group ( P<0.01). The length of single nail insertion, the number of single nail revision, and the distance between the screws and the front cortex were (6.5±0.4)minutes, (1.1±0.1)times, and (3.5±1.3)mm in the robot nailing group, which were shorter or less than (11.6±0.2)minutes, (1.5±0.2)times, and (12.4±4.7)mm in the freehand nailing group ( P<0.01). The accuracy of the screw placement in the robot nailing group was 90.0% (171/190) and 95.8% (182/190) with level 0 and 0+1 screws, better than 80.0% (240/300) and 89.0% (267/300) in the freehand nailing group ( P<0.05). There was no significant difference in VAS, JOA score, NDI, or ASIA grading between the two groups before operation ( P>0.05). The VAS, JOA, and NDI scores at 3 days after operation were (3.1±0.6)points, (12.1±1.2)points, and (15.6±2.9)points, respectively in the robot nailing group, which were better than (5.0±1.4)points, (11.3±1.1)points and (22.5±3.7)points, respectively in the freehand nailing group ( P<0.05). No statistically significant difference was observed in the ASIA grade between the two groups at 3 days after operation ( P>0.05). There were no significant differences in VAS, JOA, NDI scores, or ASIA grading between the two groups at 3 months after operation and at the last follow-up ( P>0.05). Compared with those before operation, the VAS, JOA, NDI scores, and ASIA grading were significantly improved at 3 days, 3 months after operation and at the last follow-up in the two groups, which were further improved with the passage of time. Two patients in the robot nailing group had pneumonia, with a complication rate of 9% (2/22), while 2 patients in the freehand nailing group had dural sac rupture and cerebrospinal fluid leakage and 3 had lung infection after operation, with a complication rate of 14% (5/35) ( P<0.05). Conclusion:Compared with freehand nailing, the robot system-assisted nailing revision for AS with lower cervical fracture has more advantages in terms of the operative duration, length of hospital stay, intraoperative bleeding volume, frequency of intraoperative fluoroscopy nailing speed and accuracy, screw holding force, early pain relief, function restoration, and complication rate, despite longer surgical incision.

Objective:To investigate the management of cancer pain and the clinical practices of hospice care across 11 cities in Zhejiang Province.Methods:From May 22 to 29, 2023, the Zhejiang Provincial Health Commission conducted a survey to assess the current status of hospice care practitioners regarding cancer pain management, the practices employed by medical staff in managing cancer pain, and the understanding of medical personnel concerning self-controlled analgesia for cancer pain treatment in Zhejiang Province.Results:A total of 505 questionnaires were collected from 198 hospitals across 11 cities in the province.Among the medical staff in secondary and tertiary medical institutions, 85.71%(198 out of 231)participated in the management of cancer pain in patients.Oral analgesics emerged as the most commonly used treatment for pain outbreaks, accounting for 38.53%(89 out of 231)of cases.Additionally, 37.66%(87 out of 231)of medical personnel were involved in the development of self-controlled analgesia devices within their institutions.Conclusions:In the management of cancer pain within hospice care, it is essential to enhance the theoretical training of medical staff, ensure the availability of basic analgesic medications, and establish standardized management protocols for the entire process as promptly as possible.

Objective:To investigate the effects of oxycodone on perioperative pain and cognitive function in elderly patients with colorectal cancer.Methods:A prospective randomized-controlled trial was conducted. A total of 88 elderly patients with colorectal cancer who underwent elective laparoscopic surgery at Benxi Central Hospital from June 2022 to December 2023 were selected. According to random number table method, all patients were randomly divided to the experimental group and the control group, with 44 cases in each group. Anesthesia in the experimental group was induced with oxycodone 0.2-0.3 mg/kg, intraoperative oxycodone was maintained at 0.1-0.15 mg·kg -1·h -1; oxycodone was intravenously injected with analgesia pump after surgery. In the control group, anesthesia was induced with sufentanil 0.2-0.3 μg/kg, remifentanil was intraoperatively maintained at 0.1-0.3 μg·kg -1·min -1, sufentanil was intravenously injected with analgesia pump after surgery. Blood pressure and heart rate before anesthesia induction (T 0), at tracheal intubation (T 1), at skin incision (T 2), and at extubation (T 3) of both groups were compared; numerical rating scale (NRS) at 30 minutes, 6 h, 24 h, and 48 h after surgery were scored, the confusion assessment method (CAM) and the mini-mental state examination (MMSE) score at day 1, 3, 7 after surgery were used to assess the postoperative early cognitive decline and other adverse reactions. Results:Finally, 81 patients were included in the study. There were 41 cases in the experimental group including 20 males and 21 females with the age of (76±3) years, and 40 cases in the control group including 19 males and 21 females with the age of (75±2) years. There were no statistically significant differences in gender composition, age, body mass index, operative time, intraoperative blood loss (all P > 0.05). There were statistically differences in blood pressure [(91±8) mmHg (1 mmHg = 0.133 kPa) vs. (89±10) mmHg at T 0, (92±9) mmHg vs. (90±8) mmHg at T 2, (93±9) mmHg vs. (92±9) mmHg at T 3] and heart rate [(70± 15) times/min vs.(69±16) times/min at T 0, (68±12) times/min vs. (67±12) times /min at T 2, (70± 15) times/min vs. (69±14) times/min at T 3] between the experimental group and the control group (all P > 0.05). Blood pressure and heart rate [(101±9) mmHg, (83±15) times /min] at T 1 in the experimental group were higher than those in the control group [(93±11) mmHg, (70±17) times /min], and the differences were statistically significant ( t values were 3.73, 3.77; all P < 0.001). There were no statistically significant differences in NRS scores [(2.6±1.2) scores vs. (2.8±1.1) scores at 30 min, (2.8±1.6) scores vs. (2.9±1.3) scores at 6 h, (1.8±1.2) scores vs. (2.1±1.3) scores at 24 h, and (1.5±0.7) scores vs. (1.5±0.7) scores at 48 h after surgery] between the experimental group and the control group (all P > 0.05). The incidence of postoperative early cognitive decline [4.9% (2/41) vs. 22.5% (9/40)], nausea and vomiting after surgery [7.3% (3/41) vs. 25.0% (10/40)] in the experimental group was lower than that in the control group, and the difference was statistically significant ( χ2 values were 5.36, 4.70; P values were 0.021, 0.030, respectively). Conclusions:The application of oxycodone during laparoscopic surgery can meet the needs of perioperative analgesia and improve the postoperative early cognitive function of elderly patients with colorectal cancer.

ObjectiveTo explore the differences in the accumulation of secondary metabolites of Dendrobium nobile cultivated on epiphytic stones and trees， so as to elucidate the scientific connotation of "only those that grow on stones has superior quality"， and provide a direction for the cultivation and quality evaluation of D. nobile. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS）-based widely targeted metabolomics was used to detect the metabolites of D. nobile cultivated on epiphytic stones and trees. And the combination of principal component analysis（PCA）， hierarchical cluster analysis（HCA）， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was performed for multivariate statistical analysis of metabolites. Differential metabolites were screened by variable importance in the projection（VIP） value≥1 and log₂fold change（FC）≥1 or ≤-1， and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis was conducted. ResultsA total of 1 267 metabolites were identified in the stems of D. nobile from the two cultivation modes， dominated by flavonoids（292）， phenolic acids（284）， and alkaloids（189）. Through OPLS-DA screening， 473 differential metabolites were obtained. Compared to epiphytic tree-cultivated D. nobile， epiphytic stone-cultivated D. nobile exhibited upregulation of flavonoids， phenolic acids， alkaloids， lignans and coumarins， while quinones and terpenoids were down-regulated. The differential metabolites mainly included flavonoid glycosides and alkaloids， and these differential metabolites significantly contributed to characterizing the two cultivation patterns. KEGG enrichment analysis revealed significant enrichment in pathways of flavone and flavonol biosynthesis， flavonoid biosynthesis， tyrosine metabolism， and phenylalanine metabolism in epiphytic stone-cultivated D. nobile. ConclusionEpiphytic stone cultivation is beneficial for the accumulation of phenolic acids， flavonoids， and alkaloids in D. nobile， indicating that the "only those that grow on stones has superior quality" documented in the materia medica has certain scientific basis， and the findings also provide a reference for quality evaluation and discrimination research between epiphytic stone and tree cultivated D. nobile.

BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

Microplastics and nanoplastics(MPs/NPs)are ubiquitous environmental pollutants that act as endocrine-disrupting chemicals(EDCs),raising significant concerns about their impact on human health,Research highlights the hazardous effects of MPs/NPs on both male and female reproductive systems,influencing germ cells,embryo development,and progeny.Additionally,studies show that MPs/NPs affect the gene expression of anabolic steroid hormones in vitro and in vivo,inducing reproductive toxicity through mechanisms such as oxidative stress and inflammation,Considering these adverse effects,identifying natural compounds that can mitigate the toxicity of MPs/NPs is increasingly important.Plants offer a wealth of antioxidants and anti-inflammatory compounds that can counteract these harmful effects.Among these,anthocyanins,natural colorants responsible for the vibrant hues of fruits and flowers,exhibit a wide range of biological activities,including antioxidant,anti-inflammatory,and anti-neoplastic properties.Moreover,anthocyanins can modulate sex hormone levels and alleviate reproductive toxicity.Cyanidin-3-glucoside(C3G),one of the most extensively studied anthocyanins,shows promise in reducing reproductive toxicity,particularly in females,and in protecting male reproductive organs,including the testis and epididymis.This protective effect is believed to result from its interaction with steroid receptors,specifically the androgen and estrogen receptors(ERs).These findings highlight the need to explore the mechanisms by which anthocyanins mitigate the reproductive toxicity caused by MPs/NPs.This review provides novel insights into how natural compounds can be leveraged to lessen the impact of environmental contaminants on human health,especially concerning reproductive health.