Biliary tract carcinoma （BTC） is a type of gastrointestinal tumor with a low incidence rate and a strong invasive ability， mainly including intrahepatic cholangiocarcinoma （ICC）， extrahepatic cholangiocarcinoma （ECC）， and gallbladder carcinoma （GC）， often accompanied by local progression or distant metastasis. Surgery is often the preferred treatment method for patients with local resectable tumor； however， there is still a high risk of recurrence after radical surgery. Therefore， multiple treatment modalities are often required for BTC patients， including surgical resection， systemic treatment （such as targeted therapy， chemotherapy， and immunotherapy）， and/or a combination of local treatment methods. With the development of the field of BTC， it is critical for surgical oncologists to understand and master the latest surgical strategies and the best patient selection and management systems. In view of the complexity of treatment and the continuous development of diagnosis and treatment techniques， Annals of Surgical Oncology， an authoritative American journal of cancer surgery， recently published the practical diagnosis and treatment guidelines for hepatobiliary tumors， including hepatocellular carcinoma （HCC）， ICC， ECC， and GC， aiming to provide more evidence-based evidence for the clinical management and decision-making of patients with hepatobiliary tumors. Due to the limitations of length and different emphases， this article mainly introduces the recommendations for the evaluation points and clinical treatment of ECC and GC in the guidelines， so as to provide a reference for clinical practice.

OBJECTIVE To compare the efficacy and safety of lacosamide （LCM） and carbamazepine （CAR） as monotherapy in the treatment of adult patients with newly diagnosed epilepsy. METHODS By methods of retrospective analysis， 84 adult patients with newly diagnosed epilepsy， were admitted to the Department of Neurology， Huaihe Hospital of Henan University during Sept. 2020-Jun. 2022， were divided into the control group （40 cases， receiving CAR treatment） and the observation group （44 cases， receiving LCM treatment） according to different medication regimens. Total response rate， epilepsy seizure frequency， blood lipid levels， and the occurrence of adverse events （AEs） of patients were compared between the 2 groups. RESULTS In the first month after treatment， there was no statistically significant difference in the total response rate between the observation group （63.64%） and the control group （55.00%， P＞0.05）； the frequency of epilepsy seizure in both groups was significantly reduced compared to before treatment （P＜0.05）， but there was no statistically significant difference between 2 groups （P＞0.05）. In the third month after treatment， the total response rate of the observation group （90.91%） was significantly higher than control group （67.50%， P＜0.05）； the frequencies of epilepsy seizure in both groups were significantly reduced compared to before treatment， and the observation group was significantly lower than the control group （P＜0.05）. In the third month after treatment， the levels of total cholesterol （TC）， triglyceride （TG） and low-density lipoprotein cholestrol （LDL-C） in the control group and the level of LDL-C in the observation group were significantly higher than before treatment， and the levels of TC， TG and LDL-C in the observation group were significantly lower than those in the control group （P＜0.05）. There was no statistically significant difference in the incidence of AEs between the observation group （15.91%） and the control group （17.50%， P＞0.05）. CONCLUSIONS Both LCM and CAR have certain effects in the treatment of newly diagnosed epilepsy in adults， which can reduce the frequency of epilepsy seizure in patients and have comparable safety. Meanwhile， LCM has better long-term efficacy than CAR in treating newly diagnosed epilepsy in adults， and its impact on the patient’s blood lipid is smaller than CAR.

Pathogenesis and treatment methods of qi-ying fen transformation in warm diseases are explored.It is believed that warm diseases are caused by yang pathogenic factors and are most likely to damage the organs and body fluids.Body fluids,as important components of human body's healthy qi,are usually present in the lungs as lung fluids,in the stomach as stomach fluids,in the intes-tines as intestinal fluids,and in blood vessels as nutrient yin.During the transformation from qi fen syndrome to ying fen syndrome,vis-ceral parenchymal damage acts as its important pathological mechanism and fluid depletion in blood vessels is an important reason for exacerbating qi-ying fen transformation.Excessive fire-toxicity,as an initial factor,promotes qi-ying fen transformation.Fluid deple-tion is the pathological basis for exacerbating qi-ying fen transformation.Clearing heat and protecting fluids,with sweet-flavored and cold-natured drugs to generate fluids,salty-flavored and cold-natured drugs to clear heat,and combination of sweet-flavored and bit-ter-flavored drugs,is an inevitable treatment method for preventing and treating qi-ying fen transformation in warm diseases,and it al-so has important clinical guidance value for internal miscellaneous diseases and acute severe cases.

ObjectiveSerum metabolomics of acute lung injury（ALI） in rats was conducted using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） to explore the similarities and differences in the mechanism of Qingqiao（harvested when the fruits of Forsythiae Fructus were initially ripe and still green in color） and Laoqiao（harvested when the fruits of Forsythiae Fructus were ripe） in the treatment of ALI. MethodA total of 24 SD male rats were acclimatized and fed for 1 week， 6 of them were randomly selected for the blank group and 18 for the experimental group. The ALI model was induced in the experimental group by tracheal intubation with lipopolysaccharide（LPS）. After successfully constructing the ALI model， these rats was randomly divided into model group， Qingqiao group and Laoqiao group， with 6 rats in each group. The Qingqiao and Laoqiao groups were administered orally once a day at a dose of 1.5 g·kg^-1， while the blank and model groups received an equivalent volume of saline for 3 consecutive days. The pathological conditions of rat lung tissues were comprehensively assessed by hematoxylin-eosin（HE） staining， wet-to-dry mass ratio（W/D） of lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. The levels of interleukin（IL）-6， IL-1β and tumor necrosis factor（TNF）-α in BALF were quantified using enzyme-linked immunosorbent assay（ELISA）. UPLC-Q-TOF-MS was used to identify and analyze the chemical compositions of Qingqiao and Laoqiao， and serum metabolomics of rats in each group was analyzed， combined with multivariate statistical analysis with variable importance in the projection（VIP） value>1， P<0.05 from t-test， and fold change（FC）≥1.5 or FC≤0.5 to screen the differential metabolites Qingqiao and Laoqiao for the treatment of ALI. The Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used in combination with MetaboAnalyst for the metabolic pathway analysis of the screened differential metabolites. ResultCompared with the blank group， rats in the model group exhibited enlarged alveolar lumen， ruptured alveoli， interstitial hemorrhage， bronchial exudation of a large number of neutrophils and erythrocytes， and a significant increase in the protein concentration in the BALF and the W/D value of the lung tissues（P<0.01）. In contrast， compared with the model group， rats in the Qingqiao group and the Laoqiao group showed reduced bronchial hemorrhage in the lungs， and the protein concentration in the BALF and the W/D value of the lung tissues were significantly decreased（P<0.01）， the lung injury was significantly alleviated， but more obvious in the Qingqiao group. Compared with the blank group， the expression levels of IL-6， IL-1β and TNF-α in the BALF of the model group were significantly higher（P<0.01）. Additionally， compared with the model group， the expression levels of IL-6， IL-1β and TNF-α in the Qingqiao and Laoqiao groups were significantly lower（P<0.01）. The chemical composition analysis of Qingqiao and Laoqiao revealed that 63 components were detected in Qingqiao and 55 components were detected in Laoqiao， with 47 common components， 16 components unique to Qingqiao and 8 components unique to Laoqiao. Characterizing the differences in serum metabolomics in rats， 19 and 12 metabolites were called back by Qingqiao and Laoqiao， respectively. The metabolic pathway enrichment analysis showed that Qingqiao exerted its therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， phenylalanine metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， glycerophospholipid metabolism， α-linolenic acid metabolism， and arachidonic acid metabolism， and Laoqiao exerted therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， arachidonic acid metabolism， sphingolipid metabolism， phenylalanine metabolism， ascorbate and aldarate metabolism， and glycerophospholipid metabolism. ConclusionQingqiao and Laoqiao have therapeutic effects on ALI， and Qingqiao is more effective. Both of them can play a therapeutic role in ALI by regulating amino acid metabolism and lipid metabolism， but the metabolic pathways affected by them are different.

Objective To investigate the clinical effect of transhepatic arterial chemoembolization(TACE)combined with tyrosine kinase inhibitors(TKIs)and programmed death receptors-1(PD-1)inhibitors(TACE+TKIs+PD-1 antibody)in the treatment of moderate advanced unresectable hepatocellular carcinoma(HCC).Methods The clinical data of 65 patients with moderate advanced unresectable hepatocellular carcinoma admitted to the Affiliated Hospital of North Sichuan Medical College from January 2020 to January 2022 were analyzed retrospectively.65 patients were treated with TACE+TKIs+PD-1 antibody.The observation indexes were tumor response,objective response rate(ORR),disease control rate(DCR),total survival time,progression free survival time,conversion operation rate and adverse drug reaction.Results The ORR of 65 p-atients with hepatocellular carcinoma was 49.2％(32/65),and the DCR was 89.2％(58/65).Among them,there were 2 patients with complete remission(CR),30 patients with partial remission(PR),26 patients with stable disease(SD),and 7 patients with progression disease(PD).Among 65 patients with hepatocellular carcinoma,18 patients were transformed into resectable hepatocell-ular carcinoma and underwent RO surgery.The conversion rate was 27.6％(18/65).65 patients were followed up for 3 to 22.4 months,The median follow-up time was 16.5 months.The median overall survival time and median disease progression free survival time of 65 patients were 14.5 months(95％CI:12.3～16.6 months)and 8.8 months(95％CI:6.9～10.6 months),respectively.After treatment,65 patients all had post embolism syndrome(abdominal pain,fever,nausea,vomiting and other symptoms),and some patients had transient abnormal liver function.Adverse drug reactions below grade 3 recovered within a few days.Some patients were associated with multiple adverse drug reactions.1 patient(1.5％)stopped using TACE because of stubborn vomiting,and 5 patients(7.6％)stopped using Lenvatinib because of severe liver function damage during treatment,2 patients(3％)stopped using Camrelizumab because of severe reactive capillary hyperplasia,one patient(1.5％)stopped using Tislelizumab because of severe hypothyroidism,one patient(1.5％)stopped the treatment of Lenvatinib and Sintilimab due to severe gastrointestinal bleeding.The adverse drug reactions of grade 3～4 occurred in other patients were alleviated after drug reduction,symptomatic treatment and hormone treatment.Conclusion TACE+TKIs+PD-1 antibody can obtain reliable clinical efficacy and anti-tumor activity in the treatment of moderate advanced unresectable hepatocellular carcinoma.

Objective:To investigate the clinical efficacy of single-incision plus one-port three dimensional (3D) laparoscopic pancreaticoduodenectomy (SILPD+1).Methods:The retrospective cohort study was conducted. The clinicopathological data of 40 patients who underwent 3D laparos-copic pancreaticoduodenectomy in Affiliated Hospital of North Sichuan Medical College from January to October 2023 were collected. There were 24 males and 16 females, aged (63±10)years. Of the 40 patients, 18 cases undergoing SILPD+1 were divided into the SILPD+1 group, and 22 cases under-going conventional five-trocar 3D laparoscopic pancreaticoduodenectomy (CLPD) were divided into the CLPD group. Observation indicators: (1) surgical situations; (2) postoperative situations and complications. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney rank sum test. Results:(1) Surgical situa-tions. Seventeen patients of the SILPD+1 group completed surgery successfully, and the rest of one patient with an inflammatory mass of the pancreatic head was converted to open surgery due to unclear boundary with mesenteric blood vessels and severe adhesion of surrounding tissues. All patients of the CLPD group completed surgery successfully, without conversion to open surgery. There was no significant difference in conversion to open surgery between the two groups ( P>0.05), and there was no significant difference in the volume of intraoperative blood loss, intraoperative blood transfusion or operation time ( P>0.05). (2) Postoperative situations and complications. There was no significant difference in tumor diameter, the number of lymph node dissected, the number of positive lymph node, R 0 resection, tumor type, time to postoperative first flatus, time to postopera-tive first intake liquid food, tome to first out-of-bed activity, time to postoperative drainage tube removal, duration of postoperative hospital stay, postoperative bleeding, pancreatic fistula, chylous leakage, delayed gastric emptying, abdominal fluid collection, incision infection, classification of com-plications between the two groups ( P>0.05). Postoperative pain score of the SILPD+1 group and the CLPD group was 5.0(4.5,6.0) and 6.5(6.0,7.0), respectively, showing a significant difference ( Z=-3.61, P<0.05). Both groups of patients had no occurrence of biliary fistula or abdominal infection after surgery, and there was no readmission within 30 days after surgery or no death within 90 days after surgery. Conclusions:Compared with CLPD, SILPD+1 is safe and feasible, with less postoperative pain. While ensuring oncological outcomes, SILPD+1 does not increase surgical time, postoperative hospital stay, or incidence of postoperative complications.

To discover new structural hits, based on the important role of pyrazole ring and fragment of pyridinone carboxylic acid in drug design, novel title pyrazolo[3,4-b]pyridine-4-one-5-carboxylic acid derivatives (10a-10p) were designed and synthesized, the structures were confirmed by spectral data and elemental analyses. The antibacterial and antitumor activities were evaluated by the measured minimum inhibitory concentration (MIC) values against the tested four strains and half inhibitory concentration (IC₅₀) values against the tested four cancer cells, respectively. The results displayed markedly poor antibacterial activity and observably potent antitumor activity. In particularly, the title difluorophenyl (10d, 10e, 10f), pyridyl (10j), ethyl (10k) and cycloproyl (10l) compounds exhibited comparable activity against Capan-1 and A549 cells to that of the comparison doxorubicin. Thus, pyrazolo[3,4-b]pyridine-4-one-5-carboxylic acid derivatives as promising antitumor hits need to be developed.

Objective:To observe any therapeutic effect of combining early pulmonary rehabilitation training with acupuncture at the back-shu and front-mu acupoints in treating stroke-associated pneumonia (SAP).Methods:Eighty SAP patients were randomly divided into a treatment group and a control group, each of 40. Both groups were given routine symptomatic treatment for pneumonia, nutritional support, lipid-lowering and anti-infection measures, as well as acupuncture at the back-shu and front-mu acupoints. The treatment group additionally received pulmonary rehabilitation training. Before and after 14 days of the treatment, both groups were evaluated in terms of their forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak flow rate (PEF), white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT). Chinese medicine (TCM) scores for expectoration of phlegm, shortness of breath, pulmonary rales, cough, fever and weakness were also assigned. The duration of antibiotic use and intensive care unit (ICU) stay were compared between the two groups.Results:Treatment efficacy was significantly higher in the treatment group (97.5%) than in the control group (85.0%). The treatment group′s average duration of antibiotic use and ICU stay were significantly shorter than in the control group. The treatment improved the average FVC, FEV1, PEF, WBC, CRP and PCT of both groups significantly leaving the average FVC and PEF of the treatment group significantly higher than the control group′s average, but its average WBC, CRP, PCT and the total TCM syndrome score significantly lower.Conclusions:Combining early pulmonary rehabilitation training with acupuncture at the back-shu and front-mu acupoints has a definite therapeutic effect on SAP patients. It can significantly shorten the use of antibiotics and ICU stay, promote the recovery of lung function, reduce inflammation and relieve clinical symptoms.

BACKGROUND: Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 ( MTHFD1 ) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored. METHODS: A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF Cr ) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UF Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence. RESULTS: In the high fluoride group, children's IQ scores decreased by 2.502 when the UF Cr level increased by 1.0 mg/L (β = -2.502, 95% confidence interval [CI]:-4.411, -0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group ( P   <  0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05). CONCLUSION Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.
Child ; Creatinine ; Cross-Sectional Studies ; Fluorides/urine* ; Formate-Tetrahydrofolate Ligase ; Humans ; Intelligence/genetics* ; Methylenetetrahydrofolate Dehydrogenase (NADP) ; Methylenetetrahydrofolate Reductase (NADPH2)

A series of tacrine-phenol-bifendate hybrids (7a-7e, 8a-8e) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs) with low hepatotoxicity. All the compounds had potent ChEs inhibitory activity with half-inhibitory concentration (IC₅₀) values at the nanomolar range. Compound 8d exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC₅₀ value of 156.39 nmol·L^-1 and compound 7b showed the most potent inhibition for butyrylcholinesterase with IC₅₀ value of 16.33 nmol·L^-1. Kinetic and molecular modeling studies showed that 8d targeted both the catalytic active site and the peripheral anionic site of AChE. In addition, these compounds showed low toxicity to hepatocytes, and compound 8d did not increase the level of reactive oxygen species in HepG2 cells.