The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans ; Tumor Microenvironment/drug effects* ; Neoplasms/therapy* ; Animals ; Medicine, Chinese Traditional ; Disease Progression ; Drugs, Chinese Herbal

OBJECTIVE: To explore clinical efficacy of membrane-induced technique combined with gastrocnemius muscle flap transposition in treating traumatic osteomyelitis of the upper tibia. METHODS: A retrospective analysis was conducted on 7 patients with traumatic osteomyelitis of the upper tibia who were treated with membrane-induced technique combined with gastrocnemius muscle flap transposition from January 2022 to December 2023. Among them, there were 4 males and 3 females; aged from 29 to 57 years old; 4 patients were treated after open fracture, 2 patients were treated after closed fracture, and 1 patient was treated after scalding; the courses of disease ranges from 2 weeks to 8 years; sinus tracts were present in all patients, and the lesion range of the tibia ranged from 5 to 9 cm. The results of deep tissue bacterial culture showed that 2 patients were negative, 3 patients were staphylococcus aureus, 1 patient was methicillin-resistant staphylococcus aureus, and 1 patient was pseudomonas aeruginosa and 1 patient was klebsiella pneumoniae. After debridement, the range of bone defect ranged from 8 to 12 cm, and the cortical defect accounted for approximately 30% of the circumference. The area of soft tissue defect ranged from 8.0 cm×2.0 cm to 10.0 cm×6.0 cm. At the first stage, vancomycin-loaded/meropenem/gentamicin-loaded bone cement was implanted. The gastrocnemius muscle flap was repositioned to cover the wound surface and free skin grafting was performed. After an interval of 7 to 10 weeks, the stageⅡsurgery was performed to remove bone cement. Autologous iliac bone mixed with vancomycin/gentamicin and calcium sulfate artificial bone was transplanted, and the wound was sutured. One patient retained the original internal plants, one patient removed the internal plants and replaced them with steel plate external fixation, one patient replaced the internal plants and added steel plate external fixation, and three patients were simply fixed with steel plate external fixation. One year after operation, the recovery of knee joint and ankle joint functions was evaluated by using Hospital for Special Surgery (HSS) knee joint score and Kofoed ankle joint function score respectively. RESULTS: All patients had their wounds closed simultaneously with bone cement implantation and healed well. All patients were followed up for 12 to 17 months after operation, and satisfactory bone healing was achieved at 6 months after stageⅡsurgery. Twelve months after operation, all patients had good bone healing without obvious limping was observed when walking. At 12 months after operation HSS knee joint score ranged from 93 to 100 points, and Kofoed ankle function score ranged from 96 to 100 points. CONCLUSION For traumatic osteomyelitis of the upper tibia, a staged treatment plan combining membrane-induced technique and gastrocnemius flap transposition on the basis of thorough debridement could safely cover the wound surface, effectively control bone infection and achieve satisfactory bone healing, without adverse effects on limb function.
Humans ; Male ; Female ; Middle Aged ; Osteomyelitis/surgery* ; Adult ; Surgical Flaps ; Retrospective Studies ; Tibia/injuries* ; Muscle, Skeletal/surgery*

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Purpose: To investigate the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL) in Asian men with all stages of prostate cancer. Materials and Methods: READT (real-life evaluation of the effect of ADT in prostate cancer patients in Asia) was a multi-center, prospective observational study involving six sites across four Asian populations. We enrolled eligible prostate cancer patients, who opted for ADT alone or in combination without prior neoadjuvant or adjuvant ADT within 12 months. The EuroQoL-5 dimensions, 5 level scale (EQ-5D-5L) utility index scores and visual analog scale (VAS) were evaluated at baseline, month 6 and month 12. Results: A total of 504 patients were recruited into READT between September 2016 and May 2020 with 52.9% diagnosed with metastatic prostate cancer. The EQ-5D-5L was evaluable in 442/504 (87.7%) of patients. Overall baseline EQ-5D-5L utility index score was 0.924 (interquartile range [IQR] 0.876–1.000). We observed a statistically significant difference in baseline EQ-5D-5L utility index score among different populations with a median EQ-5D-5L utility index score of 1 for Taiwan & Hong Kong, 0.897 for China and 0.838 for Malaysia. Similar trend was observed throughout multiple treatment time-points. Stage IV prostate cancer were significantly associated with a lower baseline EQ-5D-5L utility index score compared to stage I–III prostate cancer, producing a median disutility value of -0.080. Participants had a high median VAS (80, IQR 70–90), indicating good overall health on average during ADT initiation. Conclusions The study highlights the differences in health state utility index scores among various Asian prostate cancer patients receiving ADT at real-world setting. Our findings will be informative and useful in cost-effectiveness evaluation and policy decision making.

Cathartic colon （CC） is a common and refractory digestive system disease， with the pathogenesis not fully clarified. The effective therapies other than laxatives and surgery remain to be developed for CC. Therefore， establishing the CC animal models that fit the disease characteristics of western medicine and syndrome characteristics of traditional Chinese medicine （TCM） is an important link to promote the research on this disease. The fitting degree of animal models with the latest Chinese and western medical diagnostic criteria is an indicator to assess the effectiveness of the animal models in simulating the disease characteristics of western medicine and syndrome characteristics of TCM. The literature review showed that the model animals， drugs and their dosage forms， doses， administration methods， and modeling period of CC varied in different studies， and the available CC animal models presented different fitting degrees with the disease characteristics of western medicine and syndrome characteristics of TCM. Rats were the preferred animals for the modeling of CC. Rhei Radix et Rhizoma preparations were commonly used for model inducing， which， however， may cause water electrolyte disorders， decreased immunity， and even death of animals at the late stage of modeling. The animals were modeled by gradually increasing the starting dose， while the starting dose and increasing dose varied. The maintenance dose was determined based on 50% of the animals having loose stools， and the end for a cycle was determined as the time when loose stools disappeared in 80% of animals. The modeling always lasted for 2-3 cycles， approximately 2-4 months. The CC models established with Rhei Radix et Rhizoma granules and rhein had high fitting degrees with the disease and syndrome characteristics. In addition， the CC animal models of TCM syndromes were still in the exploration stage. There were only the animal models of four TCM syndromes： liver depression and spleen deficiency， both Qi and Yin deficiency， Qi stagnation and blood stasis， and spleen and kidney deficiency. Efforts should be made to establish the animal models that meet the characteristics of disease of western medicine and syndromes of TCM， so as to facilitate the research on CC mechanism and drug development.

The UPLC fingerprint of colistimethate sodium was established for the study of quality consistency.The chromatographic column was Acquity UPLC? Peptide CSH C18 (2.1 mm × 150 mm, 1.7 μm).The mobile phase A was phosphate buffer-acetonitrile (19∶1), and the mobile phase B was phosphate buffer-acetonitrile (1∶1).The mobile phase was in gradient elution at a flow rate of 0.3 mL/min.The column temperature was set at 30 °C and the detection wavelength was 210 nm.The similarity of the fingerprints was analyzed with the Similarity Evaluation System for Chromatographic Fingerprint of Tradition Chinese Medicine (Version 2012) in combination with content determination of multiple index components to evaluate the quality consistency of imported and domestic bulk drugs.The result showed that both the original and generic bulk drugs met the specified limit requirements in the European Pharmacopoeia standards, and that their UPLC fingerprints were highly similar, indicating that the quality of the two substances was consistent.Establishing a fingerprint for similarity evaluation and combining it with the results of indicator component content determination as a comprehensive evaluation method for the study of drug quality consistency of complex components has the characteristics of fast, accurate, and comprehensive, which is helpful for drug quality evaluation and provides ideas for the evaluation of antibiotic quality consistency of complex components.

Objective:To investigate the effects of ultrasound-guided serratus anterior plane block (SAPB) on hemodynamics in children with microtia undergoing auricular reconstruction.Methods:This research was a prospective randomized control study. Patients were prospectively recruited from March 2022 to July 2022 at the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Children with microtia undergoing auricular reconstruction with costal cartilage were randomly included in either a SAPB-pre group(SAPB pre-rib harvest group) or a SAPB-post group(SAPB post-rib harvest group). Both groups of children were anesthetized with combined intravenous and inhalation anesthesia. Anesthesia maintenance was provided with i. v. propofol 4-6 mg·kg -1·h -1 and remifentanil 0.1-0.3 μg·kg -1·min -1, sevoflurane at 1% concentration, and a flow rate of 2.5 L/min. During the operation, bispectral index(BIS) was maintained between 40-60, and alterations in mean arterial pressure (MAP) and heart rate (HR) were <20%, compared to the basic values. During the operation, 1% sevoflurane was inhaled to maintain anesthesia. The fluctuation of BIS, MAP, and HR was adjusted by the intraoperative infusion of remifentanil and propofol. Ultrasound-guided SAPB in the SAPB-pre group was performed by an anesthesiologist after tracheal intubation of general anesthesia. In the SAPB-post group, ultrasound-guided SAPB was performed by the same anesthesiologist before the tracheal catheter was removed at the end of the operation, and the concentration of ropivacaine was 0.25% (3 mg/kg). MAP, HR, and BIS were recorded at each time point of admission, pre-rib harvest, during-rib harvest, post-rib harvest, anesthesia extubation, leaving the room. The consumptions of propofol and remifentanil during the operation were also recorded. Continuous data were presented as Mean±SD. Non-repeated measurement parametric variables were compared using the independent samples t-test. Repeated measurement parametric variables were assessed using repeated measures analysis of variance. The same data at varying time points were compared using Dunnett- t test of multiple comparison procedures. Categorical data were compared using the Chi-square test. Results:Sixty children were randomized to SAPB-pre group and SAPB-post group and 30 in each group. The data of gender (boy 22/ girl 8 vs. boy 23/ girl 7), age[(8.03±1.07)years vs. (8.33±1.16)years], body mass index [(17.46±2.79)kg/m 2 vs. (17.23±2.11)kg/m 2], operation time[(185.33±16.29)min vs. (190.00±16.50)min] and length of costocartilage[(23.13±1.46)cm vs. (23.63±1.27)cm] between the two groups showed no significant differences ( P>0.05). There was no significant difference in MAP, HR and BIS values at the time of pre-rib harvest, during-rib harvest, and post-rib harvest in the SAPB-pre group ( P>0.05). In the SAPB-post group, the fluctuations of MAP, HR and BIS values at the time of pre-rib harvest, during-rib harvest and post-rib harvest were obvious ( P<0.01). The consumptions of propofol and remifentanil during the operation in the SAPB-pre group were significantly less than that in the SAPB-post group[(555.67±150.90)mg vs. (788.50±191.02)mg, P<0.01; (745.33±183.56)μg vs. (1 080.00±247.26)μg, P<0.01]. Conclusion:Ultrasound-guided serratus anterior plane block can stabilize the hemodynamics during auricular reconstruction using costal cartilage and reduce the consumption of general anesthetic.

Objective:To investigate the effects of ultrasound-guided serratus anterior plane block (SAPB) on hemodynamics in children with microtia undergoing auricular reconstruction.Methods:This research was a prospective randomized control study. Patients were prospectively recruited from March 2022 to July 2022 at the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Children with microtia undergoing auricular reconstruction with costal cartilage were randomly included in either a SAPB-pre group(SAPB pre-rib harvest group) or a SAPB-post group(SAPB post-rib harvest group). Both groups of children were anesthetized with combined intravenous and inhalation anesthesia. Anesthesia maintenance was provided with i. v. propofol 4-6 mg·kg -1·h -1 and remifentanil 0.1-0.3 μg·kg -1·min -1, sevoflurane at 1% concentration, and a flow rate of 2.5 L/min. During the operation, bispectral index(BIS) was maintained between 40-60, and alterations in mean arterial pressure (MAP) and heart rate (HR) were <20%, compared to the basic values. During the operation, 1% sevoflurane was inhaled to maintain anesthesia. The fluctuation of BIS, MAP, and HR was adjusted by the intraoperative infusion of remifentanil and propofol. Ultrasound-guided SAPB in the SAPB-pre group was performed by an anesthesiologist after tracheal intubation of general anesthesia. In the SAPB-post group, ultrasound-guided SAPB was performed by the same anesthesiologist before the tracheal catheter was removed at the end of the operation, and the concentration of ropivacaine was 0.25% (3 mg/kg). MAP, HR, and BIS were recorded at each time point of admission, pre-rib harvest, during-rib harvest, post-rib harvest, anesthesia extubation, leaving the room. The consumptions of propofol and remifentanil during the operation were also recorded. Continuous data were presented as Mean±SD. Non-repeated measurement parametric variables were compared using the independent samples t-test. Repeated measurement parametric variables were assessed using repeated measures analysis of variance. The same data at varying time points were compared using Dunnett- t test of multiple comparison procedures. Categorical data were compared using the Chi-square test. Results:Sixty children were randomized to SAPB-pre group and SAPB-post group and 30 in each group. The data of gender (boy 22/ girl 8 vs. boy 23/ girl 7), age[(8.03±1.07)years vs. (8.33±1.16)years], body mass index [(17.46±2.79)kg/m 2 vs. (17.23±2.11)kg/m 2], operation time[(185.33±16.29)min vs. (190.00±16.50)min] and length of costocartilage[(23.13±1.46)cm vs. (23.63±1.27)cm] between the two groups showed no significant differences ( P>0.05). There was no significant difference in MAP, HR and BIS values at the time of pre-rib harvest, during-rib harvest, and post-rib harvest in the SAPB-pre group ( P>0.05). In the SAPB-post group, the fluctuations of MAP, HR and BIS values at the time of pre-rib harvest, during-rib harvest and post-rib harvest were obvious ( P<0.01). The consumptions of propofol and remifentanil during the operation in the SAPB-pre group were significantly less than that in the SAPB-post group[(555.67±150.90)mg vs. (788.50±191.02)mg, P<0.01; (745.33±183.56)μg vs. (1 080.00±247.26)μg, P<0.01]. Conclusion:Ultrasound-guided serratus anterior plane block can stabilize the hemodynamics during auricular reconstruction using costal cartilage and reduce the consumption of general anesthetic.