Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

OBJECTIVE: To explore the construction of a canine model of vascularized allogeneic spinal cord transplantation (vASCT) and preliminarily evaluate its therapeutic efficacy for spinal cord injury (SCI). METHODS: Sixteen female Beagle dogs aged 8-12 months were randomly selected, with 8 dogs serving as donors for the harvesting of spinal cord tissue with a vascular pedicle [dorsal intercostal artery (DIA) at the T₁₀ level and accompanying vein]. The remaining 8 dogs underwent a 1.5-cm-length spinal cord defect at the T₁₀ level, followed by transplantation of the donor spinal cord tissue for repair. Polyethylene glycol (PEG) was applied to both ends to spinal cord graft; then, using a random number table method, the dogs were divided into an experimental group (n=4) and a control group (n=4). The experimental group received immunosuppressive intervention with oral tacrolimus [0.1 mg/(kg∙d)] postoperatively, while the control group received no treatment. The operation time and ischemia-reperfusion time of two groups were recorded. The recovery of hind limb function was estimated by Olby score within 2 months after operation; the motor evoked potentials (MEP) was measured through neuroelectrophysiological examination, and the spinal cord integrity was observed through MRI. RESULTS: There was no significant difference in the operation time and ischemia-reperfusion time between the two groups (P>0.05). All dogs survived until the completion of the experiment. Within 2 months after operation, all dogs in the control group failed to regain the movement function of hind limbs, and Olby scores were all 0. In the experimental group, the movement and weight-bearing, as well as walking abilities of the hind limbs gradually recovered, and the Olby scores also showed a gradually increasing trend. There was a significant difference between the two groups from 3 to 8 weeks after operation (P<0.05). Neuroelectrophysiological examination indicated that the electrical signals of the experimental group passed through the transplanted area, and the latency was shortened compared to that at 1 month after operation (P<0.05), showing continuous improvement, but the amplitude did not show significant improvement (P>0.05). The control group was unable to detect any MEP changes after operation. MRI examination showed that the transplanted spinal cord in the experimental group survived and had good continuity with normal spinal cord tissue, while no relevant change was observed in the control group. CONCLUSION The vASCT model of dogs was successfully constructed. This surgical procedure can restore the continuity of the spinal cord. The combination of tacrolimus anti-immunity is a key factor for the success of transplantation.
Animals ; Dogs ; Female ; Spinal Cord/blood supply* ; Spinal Cord Injuries/surgery* ; Transplantation, Homologous ; Disease Models, Animal ; Recovery of Function ; Plastic Surgery Procedures/methods* ; Tacrolimus ; Immunosuppressive Agents

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

This article systematically studied the moxibustion methods embedded in the 15 medical books of the Mawangdui medical literature. Starting from the origin of the medical moxibustion culture in Mawangdui， this paper comprehensively analyzed the records of moxibustion. By analyzing the Classic of Moxibustion to Eleven Foot-arm Channels （《足臂十一脉灸经》） and Classic of Moxibustion to Eleven Yin-yang Channels （《阴阳十一脉灸经》） as well as Formulas for Fifty-two Diseases （《五十二病方》）， which have relatively rich records of moxibustion， it is found that moxibustion involves more than 170 diseases and syndromes， covering 12 categories such as limb diseases related to meridians and collaterals， lung system diseases， and heart and brain diseases. In summary， the distinctive characte-ristics of moxibustion in Mawangdui medical books include primitive simplicity， combination of witch culture and medical practices， philosophical deduction， centripetal circulation， diverse moxibustion materials， extensive cove-rage of diseases and syndromes， taboos in moxibustion， and the integration of prevention and treatment. The ideas and applications of moxibustion mainly manifest in preventing diseases before they occur and preventing changes in existing diseases， distinguishing and treating each disease based on different causes， and combining treatment based on meridians， collaterals and comprehensive diseases.

Objective To analyze the implementation effect of quality control on the homepage of inpatient medical re-cords based on the background of Disease Diagnosis Related Groups(DRG).Methods A retrospective study was conducted,including a total of 20,000 medical records from Dongguan People's Hospital from 2018 to 2022.Among them,10,000 medical records from January to December 2018,before the implementation of DRG-based quality control,were included as the control group;10,000 medical records from January to December 2022,after the implementation of DRG-based quality control,were in-cluded as the observation group.The implementation effect of quality control of hospital admission medical records among different groups based on DRG was explored.Results In the control group,there were 1,943 medical records with defects,accounting for 19.43％,which affected DRG grouping in 1,000 cases(51.47％)and did not affect DRG grouping in 943 cases(48.53％).In the observation group,there were 1,316 medical records with defects,accounting for 13.16％,among which 643 cases(48.86％)affected DRG grouping and 673 cases(51.14％)did not affect DRG grouping.The difference in the number of defective medical records between the groups was statistically significant(χ2=144.11,P<0.05).The missing rates of diagnos-tic and treatment information and cost information in the observation group were lower than those in the control group(P<0.05).The completeness and accuracy rates of diagnosis and surgical information in the observation group were higher than those in the control group(P<0.05).Conclusion The implementation of quality control of hospital admission medical records based on DRG can significantly improve the quality of medical records,increase the accuracy of diagnosis and surgical information in medi-cal records,and have higher comprehensive quality control value.It is recommended for clinical promotion and use.

Objective:To investigate the applied effect of airway lavage of fiberoptic bronchoscope under computed tomography(CT)location combined with ultrasound monitoring diaphragmatic movement in mechanical ventilation of pediatric severe pneumonia.Methods:A total of 70 pediatric patients with severe pneumonia who received mechanical ventilation in The People's Hospital of Liupanshui City and Liupanshui Maternal and Child Health Care Hospital from October 2022 to October 2023 were selected,and they were divided into a control group and an observation group according to the random number table method,with 35 cases in each group.The control group did not undergo CT examination for lung before lavage with bronchoscopy,while the observation group received CT examination before airway lavage.Both two groups simultaneously adopted B ultrasound to monitor diaphragm movement.Heart rate,respiration,oxygen saturation,respiratory mechanics index,pediatric early warning score(PEWS)and modified pneumonia survivor index(mPIRO)score were detected before and after lavage,and the movement and thickness of diaphragm of children were measured by B ultrasound.Results:The heart rate and respiratory frequency of two groups after treatment were significantly lower than those before treatment,and the blood oxygen saturation was significantly higher than that before treatment.The heart rate and respiratory frequency of the observation group were respectively(80.23±10.07)times/min and(18.11±5.03)times/min,which were significantly lower than those of the control group,and the blood oxygen saturation was significantly higher than that of the control group,and the differences were statistical significance(t=3.397,3.939,7.719,P<0.05),respectively.The pulmonary pressure,peak pressure,plateau pressure,average airway pressure,chest pressure and abdominal pressure of two groups after treatment were significantly lower than those before treatment,and the levels of the above indicators in the observation group were significantly lower than those in the control group,with statistical significances(t=12.323,8.141,16.733,12.298,11.375,18.248,P<0.05),respectively.The PEWS scores and total scores of body temperature,pulse,respiration and blood pressure of two groups after treatment were significantly lower than those after treatment,and the above scores in the observation group were significantly lower than those in the control group,with statistical significance(t=67.309,58.148,35.997,30.218,5.271,P<0.05),respectively.The mPRIO scores and total scores of age,test indicators of laboratory,symptom duration,respiratory distress index and treatment plan in two groups after treatment were significantly higher than those before treatment,and the above scores in the observation group were significantly higher than those in the control group,with statistical significances(t=7.432,7.153,7.268,5.088,4.645,4.091,P<0.05),respectively.The diaphragm movement and thickness of two groups after treatment were significantly higher than those before treatment,and the above indicators in the observation group were significantly higher than those in the control group,with statistical significances(t=63.444,6.803,P<0.05),respectively.Conclusion:Compared with conventional airway lavage,the airway lavage of fiberoptic bronchoscope under CT location combined with B ultrasound of monitoring diaphragm has higher accuracy and reliability.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.