The plateau region is known for its unique environmental characteristics of low oxygen, low pressure, strong radiation, cold and dryness. Under the low oxygen environment, human physiological functions and drug metabolism are significantly affected. In order to gain a deeper understanding of drug metabolism in the plateau hypoxic environment and to guide the rational use of drugs in the plateau region, the effects of plateau hypoxia on drug metabolism were reviewed in this paper, which focused on changes in metabolic profiles, enzyme activity and expression, and probed the relevant mechanisms in depth.

The plateau region is known for its unique environmental characteristics of low oxygen, low pressure, strong radiation, cold and dryness. Under the low oxygen environment, human physiological functions and drug metabolism are significantly affected. In order to gain a deeper understanding of drug metabolism in the plateau hypoxic environment and to guide the rational use of drugs in the plateau region, the effects of plateau hypoxia on drug metabolism were reviewed in this paper, which focused on changes in metabolic profiles, enzyme activity and expression, and probed the relevant mechanisms in depth.

B and T lymphocyte attenuator (BTLA) is an inhibitory immune checkpoint, which typically interacts with herpesvirus entry mediator (HVEM) and plays a crucial role in regulating immune balance. BTLA interacts with its ligand HVEM in a cis manner on the surface of the same immune cell to maintain immune tolerance, while trans interactions on the surface of different immune cells mediate immunosuppressive effects. Dysregulation of the BTLA/HVEM axis can impair the functions of immune cells, particularly T lymphocytes, promoting immune escape of tumor cells and ultimately leading to tumor progression. Researchers have found that BTLA and HVEM are abnormally expressed in various tumors and are associated with prognosis, suggesting that they may be potential targets for tumor immunotherapy. This review summarizes the molecular structures of BTLA and HVEM, immunomodulatory mechanisms, recent advances in hematologic malignancies, potential inhibitors of BTLA/HVEM interaction, and their applications in immunotherapy for hematologic malignancies.
Humans ; Receptors, Tumor Necrosis Factor, Member 14/chemistry* ; Receptors, Immunologic/immunology* ; Hematologic Neoplasms/genetics* ; Immunotherapy/methods* ; Animals

Objective:To evaluate the feasibility and safety of performing multi-procedure remote urological surgeries by integrating 5G communication technology with domestically manufactured robotic surgical systems.Methods:Patients requiring urological laparoscopic surgery for benign lesions or tumors were prospectively enrolled at Gansu Provincial Hospital from May 2023 to June 2024. Inclusion criteria included age ≥18 years, body mass index (BMI) between 18 and 30 kg/m 2, and American Society of Anesthesiologists (ASA) classification Ⅰ-Ⅲ. Tumor-related surgical indicators were as follows: renal tumors staged ≤T 2, solitary tumors, or maximum diameter ≤10 cm; intermediate- to low-risk prostate cancer (clinical stage ≤T 2b), with preoperative prostate-specific antigen (PSA) ≤20 ng/ml or Gleason score ≤7; adrenal tumors with a diameter ≤7 cm or ≥3 cm for non-functional adenomas; and bladder tumors staged ≤T 2. Exclusion criteria included participation in other investigational drug or device clinical trials within the past 1 month, pregnancy or breastfeeding, and patients requiring emergency surgery. Patients with severe cardiovascular or circulatory diseases contraindicating surgery, and individuals with epilepsy, psychiatric disorders, or cognitive impairments were also excluded. Additionally, patients with active bleeding, coagulation disorders, or platelet counts <80×10 9/L were excluded. A 5G communication link was established between the main campus and the new branch of Gansu Provincial Hospital, approximately 70 km apart. Remote surgeries were performed using the domestically manufactured robotic surgical system (Toumai MT-1000). Perioperative key indicators, intraoperative network conditions, and robotic system performance were systematically recorded. Results:This study involved 14 patients, comprising 3 cases of renal cysts, 3 cases of renal tumors, 3 cases of nonfunctional kidneys, 2 cases of adrenal tumors, 1 case of bladder tumor, 1 case of prostate cancer, and 1 case of ureteral-bladder wall thickening with pelvic ureteral stones. The cohort included 7 male and 7 female patients, with an average age of (57.4±12.3) years, a BMI of (24.6±3.0) kg/m 2, and ASA classifications of grade Ⅱ in 9 cases and grade Ⅲ in 5 cases. All remote surgeries were successfully completed without the need for conversion to alternative surgical methods. Three renal cyst unroofing decompression procedures were performed, with an average console operation time of (32.0±6.6) minutes and intraoperative blood loss of (13.3±2.9) ml. Two partial nephrectomies were conducted, with console operation times of 140 and 160 minutes, intraoperative blood loss of 20 ml each, and warm ischemia times of 19 and 25 minutes, respectively. The preoperative estimated glomerular filtration rates (eGFR) for these cases were 115.2 and 107.3 ml/(min·1.73m 2), and postoperative eGFR were 102.0 and 95.5 ml/(min·1.73m 2), respectively. Four radical nephrectomies were completed, with an average console operation time of (50.2±13.7) minutes and intraoperative blood loss of (20.5±13.2) ml. Two adrenal tumor resections were performed, each with console operation times of 45 and 50 minutes and intraoperative blood loss of 10 ml. Additionally, one partial bladder resection was conducted, requiring a console operation time of 60 minutes and resulting in intraoperative blood loss of 10 ml. A single radical prostatectomy was carried out, with a console operation time of 180 minutes, intraoperative blood loss of 120 ml, and pre- and postoperative PSA levels of 11.7 ng/ml and 0.06 ng/ml, respectively. One ureteral-bladder reimplantation was also performed, with a console operation time of 240 minutes and intraoperative blood loss of 10 ml. The average total delay for the 14 remote surgeries ranged from 194 to 250 ms, while the average network transmission delay ranged from 13 to 55 ms. During the procedures, six instances of sudden large fluctuations in network transmission delay were observed, ranging from 333 to 654 ms. These fluctuations resolved automatically within approximately 10 seconds but resulted in temporary disruptions: 2 cases of master-slave console lock (reset process lasted around 5 seconds) and 1 case of switching to the local console for emergency hemostasis (lasting approximately 7 minutes). These interruptions did not significantly affect the surgical process. Postoperative complications in all patients were classified as Clavien-Dindo grade Ⅰ and were unrelated to the surgical procedures or equipment. No cancer was detected in the resection margins of malignant tumors. Follow-up evaluations at three months, including blood tests, liver and kidney function tests, and CT scans of the surgical sites, revealed no significant abnormalities or adverse events. Conclusions:5G communication technology, with an average total latency of less than 250 ms, enables domestic surgical robots to perform multi-procedural remote urological surgeries effectively. However, during procedures requiring extensive suturing for urological reconstruction or managing unplanned intraoperative bleeding, network latency fluctuations exceeding 333 ms can extend the operation time and may necessitate switching to local control for emergency hemostasis.

This article presents the diagnosis and treatment processes, and morphological and genetic testing of Gongylonema pulchrum in a case with G. pulchrum found in the oral mucosa. In addition, this article reviews publications pertaining to G. pulchrum human infections by Chinese scientists during the recent 10 years and summarizes the demographic and clinical characteristics, location and number of parasites, diagnosis and treatment processes, and epidemiological surveys of cases infected with G. pulchrum, so as to provide insights into improving the diagnostic capability among clinicians.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

Objective:To construct a risk prediction model for hemorrhagic transformation (HT) in elderly patients with acute cerebral infarction (ACI) complicated by cerebral small vessel disease (CSVD) based on thromboelastography (TEG) and coagulation function indicators.Methods:Clinical data of 120 elderly ACI patients with CSVD admitted to the First Affiliated Hospital of Xi′an Jiaotong University from June 2021 to June 2024 were retrospectively analyzed. Patients were divided into HT group (42 cases) and non-HT group (78 cases) according to the occurrence of HT within 7 days of admission. TEG parameters, coagulation function indicators, and general data were compared between the two groups. Multivariate logistic regression analysis was used to screen the influencing factors of HT, and a nomogram model was constructed accordingly. The receiver operating characteristic (ROC) curve was used to evaluate its predictive efficacy.Results:Compared with the non-HT group, the HT group had significantly longer coagulation reaction time (R), higher 30-minute clot lysis rate (LY30), longer activated partial thromboplastin time (APTT), older age, higher prevalence of diabetes mellitus, higher National Institutes of Health Stroke Scale (NIHSS) score, and larger infarct size, while the fibrinogen (FIB) level was lower (all P<0.05). Multivariate stepwise logistic regression showed that R ( OR=3.295, 95% CI: 1.226-8.848), LY30 ( OR=6.118, 95% CI: 3.111-12.030), FIB ( OR=0.213, 95% CI: 0.085-0.527), NIHSS score ( OR=4.061, 95% CI: 1.431-11.520), and infarct size ( OR=5.314, 95% CI: 2.588-10.909) were independent influencing factors for HT in elderly ACI patients with CSVD (all P<0.05). The C-index of the nomogram model constructed based on the above factors was 0.836, and the calibration curve for predicting HT was close to the ideal curve ( P>0.05). ROC curve analysis showed that the model had a sensitivity of 85.70%, specificity of 83.30%, and area under the curve (AUC) of 0.879 (95% CI: 0.810-0.949, P<0.05) for predicting HT. Conclusions:R, LY30, and FIB levels are influencing factors for HT in elderly ACI patients with CSVD. The nomogram model constructed based on these factors can effectively predict the risk of HT.

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Purpose To investigate the incidence and risk of malignancy(ROM)of the Bethesda class Ⅰ/Ⅲ di-agnosis of thyroid nodules due to insufficient number of follicular cells,and to analyze the correlation between their in-sufficient cell volume and the characteristics of the nodules themselves from the perspective of ultrasound and histology.Methods Clinical data were collected from fine needle aspiration cytology(FNAC)of the thyroid gland.Review and statistical analysis was performed on cases with the Bethesda class Ⅰ/Ⅲ diagnosis due to insufficient cell volume.The incidence and the ROM of Bethesda class Ⅰ/Ⅲ diagnosis were calculated.BRAF V600E(+)or postoperative patho-logical indicating papillary thyroid carcinoma(PTC)was used as the criterion for malignancy.Then,we matched the Bethesda class Ⅱ/Ⅵ cases with sufficient cell volume as the control group.The ultrasound characteristics and histo-logical images of the two groups were compared and analyzed in order to reveal the correlation between the insufficient amount of penetrating cells and the objective characteristics of the nodule itself.Results There were 39 solid thyroid nodules with the Bethesda class Ⅰ diagnosis,with an incidence of 3.3％and a ROM of 38.5％,and 160 nodules with the Bethesda class Ⅲ diagnosis,with an incidence of 13.5％and a ROM of 59.4％.The incidence and ROM of nod-ules with C-TIRADS ≥4b(22.4％,67.6％)were higher than those of C-TIRADS ≤4a(12.7％,39.8％),and the differences were statistically significant(P＜0.001).Compared to the Bethesda class Ⅱ/Ⅵ nodules with sufficient cell volume,occurrence of the Bethesda class Ⅰ/Ⅲ nodules were significantly correlated with small nodules(maximal diameter＜5 mm),vertical growth(aspect ratio ≥ 1)and poor blood supply(no or little blood flow signals)(r=0.131,-0.230,0.237,P=0.008,＜0.001,＜0.001).They were also significantly correlated with the pathologic histologic structure of diffuse significant fibrosis of the interstitium and low parenchyma/interstitium composition ratio(about 1:1)(r=-0.269,-0.396,P=0.019,＜0.001).Conclusion Thyroid Bethesda class Ⅰ/Ⅲ nodules have a high ROM,and BRAF V600E detection is recommended as a tool of tiered management.Bethesda class Ⅰ/Ⅲ diagnosis of insufficient cell volume is more likely when the nodules are too small,grow vertically and lack blood sup-ply,presumably associated with extensive interstitial fibrosis and sparse parenchymal cells.