OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective To construct mice hepatocellular carcinoma models with different tumor immune microenvironments(TIME)and explore the differences.Methods H22 and hepa1-6 were used to construct subcutaneous transplantation tumor model of C57 mice as homologous hepatocellular carcinoma cell lines(denoted as H22 group and hepal-6 group,each n=8),and the differences of TIME were evaluated.Immunohistochemistry was used to detect and quantify the infiltration of T cells,CD4+T cells,CD8+T cells,regulatory T cells and B cells in TIME.Flow cytometry was performed to detect the differences of composition of immune cell subpopulations in peripheral blood and tumor parenchyma.Gene expression profile characteristics of tumor tissue were analyzed based on high-throughput transcriptome sequencing technology,and enrichment analyses of immune-related signaling pathways were evaluated combined with gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG).Results H22 group showed cold and hepa1-6 group showed hot TIME characteristics.The number of T cells,CD4+T cells and CD8+T cells in tumor tissue of H22 group were all lower,while the proportion of T cells,CD4+T cells and CD8+T cells in peripheral blood were all higher than those of hepa1-6 group(all P＜0.05).Compared with H22 group,up-regulated genes of tumor tissue in hepa1-6 group expressed significantly enriched in tumor immune activation-related signaling pathways.Conclusion H22 and hepa1-6 hepatocellular carcinoma models showed distinct TIME characteristics of cold and hot tumors,respectively,and the amount of immune cells in tumor tissue of the former were significantly lower than those in the latter.

This is a case report of bilateral Gustilo ⅢC fracture with tibial defects in both legs and combined with defects of soft tissue. The injury was treated by emergency surgery in November 2021 in the Hand and Foot Microsurgery Hospital, Xi'an Fengcheng Hospital. It was found that annular avulsion injury with partial defect of soft tissue in left leg from under the knee to ankle (10.0 cm × 4.0 cm, 14.0 cm × 8.0 cm), distal tibia-fibula fractures and partial bone defect of tibia (6.0 cm), anterior tibial artery and posterior tibial artery rupture, and posterior tibial nerve and foot were both intact. Of the right leg, it was found that there was an annular avulsion injury with partial defect of soft tissue between 1/3 of proximal leg and above ankle (25.0 cm × 10.0 cm), distal tibia-fibula fractures and partial tibial defect (4.0 cm), anterior tibial artery was ruptured and the posterior tibial artery was embolised, but posterior tibial nerve and foot were both intact. There was no blood supply in both feet. A chimeric fibular flap of right peroneal artery (15.0 cm × 6.0 cm, and the excised fibula was 13.0 cm long) was harvested and further divided into 2 chimeric flaps for reconstruction of the defects of bilateral tibia and soft tissue. A chimeric flap pedicled with descending branch of left lateral circumflex femoral artery (29.0 cm × 8.0 cm) was harvested and further divided into 2 chimeric tissue flaps pedicled with the descending branch of lateral circumflex femoral artery to cover the remaining wounds of both calves. The proximal peroneal artery was anastomosed with anterior tibial artery, and the distal peroneal artery was anastomosed with the lateral circumflex femoral artery carried by chimeric flap, and bilateral posterior tibial arteries were bridge anastomosed with the great saphenous veins. All patients were entered in the scheduled follow-up at 4, 8 and 12 weeks after surgery. The walking and the movement of ankles and toes were gradually recovered. At 1 year after surgery, the patient was able to get of the bed by himself. Plantar sensation regained to S 4 and there was a slight limb in walking, but without pain, wear or ulceration in feet.

AIM:This study aims to investigate the impact of chronic kidney disease(CKD)on the growth,development,and cognitive function of offspring rats,and to evaluate the effects of esaxerenone(ESAX)intervention.METHODS:Thirty female non-pregnant Wistar rats were randomly assigned to three groups:sham operation+pregnancy(control group),UUO+pregnancy(model group),and UUO+pregnancy+esaxerenone(treatment group),with 10 rats in each group.CKD was induced in the UUO+pregnancy and UUO+pregnancy+esaxerenone groups by performing uni-lateral ureteral obstruction(UUO),while the sham operation+pregnancy group underwent a non-ligated and non-clipped ureter procedure.Rats in the treatment group received esaxerenone at a dosage of 1 mg·kg-1·d-1.Vaginal smears were per-formed weekly from the 8th week post-UUO to monitor the estrous cycle.Female and male rats in pre-estrus or estrus were paired in a 2∶1 ratio,and the day with the first appearance of sperm in vaginal smears was recorded as the first day of preg-nancy.Offspring were delivered 21 to 22 days post-gestation,and 10 offspring from each group were selected for further experimentation:sham-offspring(sham-offspr)group,UUO-offspro group,and esaxerenone treatment offspring(ESAX-offspr)group.At 21 days of age,offspring weight and tail length were measured.Behavioral tests,including the open field test,Y maze test,and Morris water maze test,assessed learning and memory abilities.Serum levels of aldosterone,5-hydroxytryptamine(5-HT),and brain-derived neurotrophic factor(BDNF)were measured using ELISA.Serum creati-nine(SCr)and blood urea nitrogen(BUN)levels were assessed using conventional biochemical methods.Renal pathology was examined using Hematoxylin-Eosin(HE)staining.RESULTS:Offspring in the UUO-offspr group had reduced body weight and tail length compared to the sham-offspr group(P＜0.05).Behavioral tests indicated that exploration and memo-ry abilities were significantly impaired in the UUO-offspr group compared to the sham-offspr group(P＜0.05),while the ESAX-offspr group showed improved behavioral development compared to the UUO-offspr group(P＜0.05).ELISA results revealed decreased levels of serum 5-HT,BDNF,and aldosterone in the UUO-offspr group compared to the sham-offspr group(P＜0.01),with increased levels in the ESAX-offspr group(P＜0.05).Renal function tests showed elevated SCr and BUN levels in the UUO-offspr group compared to the sham-offspr group(P＜0.01),while levels in the ESAX-offspr group were reduced(P＜0.01).HE staining demonstrated mild tubular dilation and inflammatory cell infiltration in the UUO-offspr group,whereas the ESAX-offspr group had well-arranged tubules with reduced inflammation.CONCLU-SION:Chronic kidney disease adversely affects the growth,development,and cognitive function of offspring rats by 21 days of age.Esaxerenone intervention can mitigate these detrimental effects on growth,development,and cognitive abili-ties in offspring rats.

Objective Based on the traditional Chinese medicine theory of"simultaneous regulation of the liver and kidney,"this study integrated network pharmacology prediction,molecular docking,and animal experimental validation to analyze the multi-target regulatory network of Duzhong Xionghua(the male flower of Eucommia ulmoides)-Sanqi Hua(Sanchi flower)herb pair(hereinafter called"herb pair")in modulating glucolipid metabolic disorders in type 2 diabetes mellitus(T2DM),thereby elucidating its underlying molecular mechanism.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,China National Knowledge Infrastructure,VIP Database for Chinese Technical Periodicals,and Wanfang Data were used to obtain the active ingredients of the male flower of Eucommia ulmoides and Sanchi flower.PubChem Compound,SwissTargetPrediction,and SuperPred were used to screen and predict the targets of the drugs;The Human Gene Database,The Online Mendelian Inheritance in Man,and Therapeutic Target Database were used to screen the key gene targets of T2DM.A"component-target-pathway"network diagram was constructed using Cytoscape software,and Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were employed to identify the functions of the relevant target genes and pathways.Molecular docking was used to verify the binding activities of the core components and the key targets.For animal experiments,spontaneous T2DM model mice were used,in which the normal group consisted of six mice(wild type)from the same litter,and the 24 successfully modeled mice were randomly divided into model,metformin(0.26 g/kg),high-dose herb pair(2.6 g/kg),and low-dose herb pair groups(1.3 g/kg)according to the blood glucose levels and body weights,with six mice per group.The drugs were administered by gavage daily for six consecutive weeks.The body weight and fasting blood glucose(FBG)levels were measured weekly,and an oral glucose tolerance test was performed in the fifth week.At the end of drug administration,body weight,naso-anal length,liver and bilateral epididymal adipose mass were measured;pathological changes in the liver were observed using HE staining;serum levels of aspartate transaminase(AST),alanine amino-transferase(ALT),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected using colorimetric assay;and liver tissue phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3β(GSK-3β)signaling pathway protein expressions were determined using Western blotting.Results Network pharmacology screening identified 38 active components and 669 potential targets of the herb pair.Intersection analysis with 1,275 T2DM-related targets yielded 185 common targets.Protein-protein interaction network analysis and pathway enrichment revealed the PI3K/AKT signaling pathway as a key mechanism.Molecular docking confirmed the strong binding affinity of the core components to key targets such as AKT1,suggesting that the herb pair may activate the PI3K/AKT pathway and inhibit GSK-3β activity via beta-sitosterol etc.Animal experiments demonstrated that,compared with the model group,the metformin group exhibited reduced FBG,AST,and ALT levels(P<0.01),but failed to improve body weight,Lee's index,or epididymal fat coefficient.Both herb pair doses significantly lowered Lee's index,hepatic index,and the epididymal fat coefficient(P<0.01),with the low-dose herb pair group showing attenuated body weight gain in mice.In contrast,the high-dose herb pair group exhibited decreased FBG,improved glucose tolerance,reduced TC,TG,and LDL-C levels,and increased HDL-C level(all P<0.01).HE staining revealed that all metformin and the herb pair markedly restored hepatic structure and alleviated steatosis in model mice,with more pronounced effects in the high-dose group than in the low-dose group.Western blotting result indicated that in the low-dose herb pair group,phospho-PI3K(p-PI3K),AKT,and phospho-GSK-3β(p-GSK-3β)protein expressions significantly increased(P<0.05 or P<0.01),whereas GSK-3β decreased(P<0.05).The high-dose group exhibited enhanced PI3K,p-PI3K,AKT,phospho-AKT,and p-GSK-3β protein expressions(all P<0.01),accompanied by reduced GSK-3β expression(P<0.01).Conclusion The male flower of Eucommia ulmoides-Sanchi flower herb pair may ameliorate T2DM-related glucolipid metabolic disorders by modulating the PI3K/AKT/GSK-3β pathway.

Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.

Objective To explore the characteristics and prognosis of follicular lymphoma(FL)with bulky disease under rituximab-based first-line treatment.Methods A retrospective analysis was conducted on 525 FL patients diagnosed between September 2009 and September 2021 who received rituximab as a first-line treat-ment[342 patients received rituximab combined with chemotherapy(R-chemo),183 patients received rituximab plus lenalidomide(R2)].The clinicopathologic characteristics,gene mutations,and prognosis of bulky FL patients were analyzed.Results Compared to non-bulky FL patients,bulky FL patients had a significantly higher proportion of lymph node≥5 sites,≥2 extranodal involvement,bone marrow involvement,elevated LDH,and a higher proportion in the high-risk group of FLIPI1 and FLIPI2.Gene sequencing revealed a significantly higher mutation rate of ZNF608 in bulky FL patients compared to non-bulky FL patients.In patients receiving R-chemo as the first-line treatment,there was no significant difference in progression-free survival(PFS)and overall survival(OS)between bulky and non-bulky FL patients.However,in patients treated with R2,the PFS and OS of bulky FL patients was significantly shorter.Conclusions Bulky FL patients compared to non-bulky FL patients have a significantly higher proportion of high-risk baseline characteristics.For bulky FL at diagnosis,chemo-free regimens require further exploration on the basis of R2.

This is a case report of bilateral Gustilo ⅢC fracture with tibial defects in both legs and combined with defects of soft tissue. The injury was treated by emergency surgery in November 2021 in the Hand and Foot Microsurgery Hospital, Xi'an Fengcheng Hospital. It was found that annular avulsion injury with partial defect of soft tissue in left leg from under the knee to ankle (10.0 cm × 4.0 cm, 14.0 cm × 8.0 cm), distal tibia-fibula fractures and partial bone defect of tibia (6.0 cm), anterior tibial artery and posterior tibial artery rupture, and posterior tibial nerve and foot were both intact. Of the right leg, it was found that there was an annular avulsion injury with partial defect of soft tissue between 1/3 of proximal leg and above ankle (25.0 cm × 10.0 cm), distal tibia-fibula fractures and partial tibial defect (4.0 cm), anterior tibial artery was ruptured and the posterior tibial artery was embolised, but posterior tibial nerve and foot were both intact. There was no blood supply in both feet. A chimeric fibular flap of right peroneal artery (15.0 cm × 6.0 cm, and the excised fibula was 13.0 cm long) was harvested and further divided into 2 chimeric flaps for reconstruction of the defects of bilateral tibia and soft tissue. A chimeric flap pedicled with descending branch of left lateral circumflex femoral artery (29.0 cm × 8.0 cm) was harvested and further divided into 2 chimeric tissue flaps pedicled with the descending branch of lateral circumflex femoral artery to cover the remaining wounds of both calves. The proximal peroneal artery was anastomosed with anterior tibial artery, and the distal peroneal artery was anastomosed with the lateral circumflex femoral artery carried by chimeric flap, and bilateral posterior tibial arteries were bridge anastomosed with the great saphenous veins. All patients were entered in the scheduled follow-up at 4, 8 and 12 weeks after surgery. The walking and the movement of ankles and toes were gradually recovered. At 1 year after surgery, the patient was able to get of the bed by himself. Plantar sensation regained to S 4 and there was a slight limb in walking, but without pain, wear or ulceration in feet.

AIM:To investigate the possible mechanism how orphan nuclear receptor 4A1(NR4A1)affects renal fibrosis in unilateral ureteral obstruction(UUO)mice.METHODS:(1)Specific pathogen-free(SPF)male C57BL/6J mice(5 to 6 weeks old)were randomly divided into sh-Con+sham group(n=6),sham+sh-NR4A1 group(n=6),sh-NR4A1+UUO group(n=6),and sh-NR4A1+UUO group(n=6).Renal NR4A1 knockdown mice were prepared by intrarenal injection of NR4A1 viral vector.(2)SPF male C57BL/6J mice(5 to 6 weeks old)were randomly assigned to in sham group,UUO group,and UUO+cytosporone-B(Csn-B)group.An animal model of renal fibrosis was prepared by UUO,and Csn-B was intervened for 14 days.HE,Masson,and Sirius red staining were used to observe renal pathological damage.Immunohistochemistry and Western blot were performed to detect the expression of NR4A1,interferon-γ(IFN-γ),α-smooth muscle actin(α-SMA)and vimentin.The purpose of this study is to observe the regulatory effect of NR4A1 on UUO-induced renal fibrosis.RESULTS:(1)The expression of NR4A1 was decreased in kidney tissues of UUO mice(P<0.05).(2)HE staining results showed that there are tubular dilation,atrophy,and massive inflammatory cell infiltra-tion in sh-Con+UUO group,and NR4A1 knockdown can aggravate UUO-induced kidney damage(P<0.05).The results of Masson and Sirius red staining showed a banded distribution of collagen deposition in the sh-Con+UUO group,and colla-gen deposition increased significantly after NR4A1 knockdown(P<0.05).Treatment with Csn-B could improve renal path-ological damage and reduce collagen deposition.(3)UUO could upregulate the expression of α-SMA and vimentin,and NR4A1 knockdown could significantly increase UUO-induced their expression(P<0.05).In addition,Csn-B could im-prove UUO-induced renal fibrosis(P<0.05).(4)The expression of IFN-γ was increased in UUO mice,and NR4A1 knockdown could upregulate UUO-induced IFN-γ expression(P<0.05).Moreover,Csn-B could down-regulate UUO-in-duced IFN-γ expression(P<0.05).CONCLUSION:NR4A1 can affect renal fibrosis by regulating IFN-γ in UUO mice.