Objective:Acoustic neuroma(AN)is a benign tumor that usually affects a patient's hearing and balance function.For the screening and diagnosis of AN,the traditional approach mainly relies on audiological examination and magnetic resonance imaging(MRI),often ignoring the importance of vestibular function assessment in the affected area.As an emerging method of vestibular function detection,video head impulse test(vHIT)has been widely used in clinic,but research on its use in AN diagnosis is relatively limited.This study aims to explore the value of vHIT in the diagnosis of AN,vestibular dysfunction assessment,and postoperative compensation establishment in unilateral AN patients undergoing unilateral AN resection through labyrinthine approach. Methods:This retrospective study was conducted on 27 AN patients who underwent unilateral AN resection via labyrinthine approach from October 2020 to March 2022 in the Department of Otolaryngology-Head and Neck Surgery,the Second Xiangya Hospital,Central South University.vHIT was performed 1 week before surgery to assess vestibular function,pure tone audiometry(PTA)was used to assess hearing level,and ear MRI was used to assess tumor size.Follow-up vHIT was conducted at 1 week,1 month,6 months,and 1 year post-surgery.The correlation of vHIT with hearing and tumor size was analyzed. Results:Preoperative vHIT showed that the posterior semicircular canal on the affected side was the most common semicircular canal with reduced vestibulo-ocular reflex(VOR)gain.There was a correlation between the VOR gain of vHIT on the affected side and the hearing level(r=-0.47,P<0.05)or tumor size(r=-0.54,P<0.01).The results of vHIT on the affected side showed that the hearing level and mean VOR gain of the anterior semicircular canal increased slightly with time,and the amplitude and saccade percentage of the dominant saccades of the 3 semicircular canals increased,while the latency time decreased,with the most obvious changes occurring 1 week post-surgery. Conclusion:vHIT can effectively monitor the changes of vestibular function in AN patients before and after surgery and has application value in assisting the diagnosis of vestibular dysfunction in AN patients.

Objective To analyze the level of 25-hydroxyvitamin D[25(OH)D]in patients with type 2 diabetes mellitus,and preliminarily investigate the correlation between serum 25(OH)D level and metabolic indicators such as glycosylated hemoglobin(HbA1c)and pancreatic islet function in patients with type 2 diabetes mellitus.Methods A total of 459 patients with type 2 diabetes mellitus who were hospitalized in the Department of Endocrinology,Xinxiang First People's Hospital from January 2020 to December 2020 were selected as the research subjects.Clinical data of the patients were collected,including gender,age,serum 25(OH)D,fasting insulin,C-peptide,HbA1c,fasting blood glucose,postprandial blood glucose,urinary microalbumin,urinary albumin-to-creatinine ratio,blood calcium,blood uric acid(UA),triglyceride(TG),total cholesterol(TCH),low-density lipoprotein(LDL),and high-density lipoprotein(HDL).According to the serum 25(OH)D level,the patients were divided into sufficient group[n=20,25(OH)D≥30 μg·L-1],insufficient group[n=95,20 μg·L-125(OH)D＜30 μg·L-1],deficient group[n=231,10 μg·L-1 ≤25(OH)D＜20 μg·L-1],and severely deficient group[n=113,25(OH)D＜10 μg·L-1].Differences in metabolic indicators of patients in the four groups were compared,and the correlation between 25(OH)D level and metabolic indicators was analyzed by using the Pearson correlation.Results The serum 25(OH)D level of patients with type 2 diabetes mellitus was 3.00-46.59(15.75±0.35)μg·L-1;the serum 25(OH)D level of male patients was significantly higher than that of female patients(P＜0.05).The prevalence of 25(OH)D deficiency in patients with type 2 diabetes mellitus was 74.9％(344/459).The 25(OH)D deficiency mainly occurred in January,February,March,April,November,and December.Patients in the insufficient,deficient,and severely deficient groups had significantly higher HbA1c levels than those in the sufficient group(P＜0.05),and the HbA1c levels of patients in the deficient and severely deficient groups were significantly higher than those in the insufficient group(P＜0.05);there was no statistically significant difference in the HbA1c level between the deficient group and the severely deficient group(P＞0.05).There was no statistically significant difference in fasting blood glucose between the sufficient group and insufficient group,and between the deficient group and severely deficient group(P＞0.05);fasting blood glucose of patients in the deficient and severely deficient groups was significantly higher than that in the sufficient and insufficient groups(P＜0.05).There was no statistically significant difference in fasting insulin,urinary microalbumin,daily total urinary albumin,and urinary albumin-to-creatinine ratio of patients among the sufficient,insufficient,and deficient groups(P＞0.05);the fasting insulin of patients in the severely deficient group was significantly lower than that in the sufficient,insufficient,and deficient groups(P＜0.05);the urinary microalbumin,daily total urinary albumin,and urinary albumin-to-creatinine ratio of patients in the severely deficient group were significantly higher than those in the sufficient,insufficient,and deficient groups(P＜0.05).There was no statistically significant difference in the homeostasis model assessment for insulin resistance(HOMA-IR),serum albumin,blood creatinine,1-hour postprandial blood glucose,2-hour postprandial blood glucose,3-hour postprandial blood glucose,fasting C-peptide,1-hour postprandial C-peptide,2-hour postprandial C-peptide,3-hour postprandial C-peptide,TG,TCH,LDL,HDL,blood UA,and blood calcium of patients among the four groups(P＞0.05).Pearson correlation analysis showed that serum 25(OH)D levels in patients with type 2 diabetes mellitus were negatively correlated with HbA1c,urinary microalbumin,and urinary albumin-to-creatinine ratio(r=-0.093,-0.166,-0.157;P＜0.05),and positively correlated with fasting insulin(r=0.089,P＜0.05).Serum 25(OH)D levels in patients with type 2 diabetes mellitus had no correlation with fasting blood glucose,HOMA-IR,serum albumin,blood creatinine,1-hour postprandial blood glucose,2-hour postprandial blood glucose,3-hour postprandial blood glucose,fasting C-peptide,1-hour postprandial C-peptide,2-hour postprandial C-peptide,3-hour postprandial C-peptide,TG,TCH,LDL,HDL,blood UA,and blood calcium(P＞0.05).Conclusion 25(OH)D deficiency and insufficiency are common in patients with type 2 diabetes mellitus,especially in female patients.In patients with type 2 diabetes mellitus,25(OH)D level is positively correlated with fasting insulin and negatively correlated with HbAlc,urinary microalbumin,and urinary albumin-to-creatinine ratio.25(OH)D deficiency in patients with type 2 diabetes mellitus is mainly distributed in January,February,March,April,November,and December.

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

Ethnic medicine has a rich history of application. Because of the large number of ethnic groups, wide geographical distribution, and unique medical systems in China, the research on the human use experience(HUE) of ethnic medicine should combine the characteristics of ethnic medicine, be based on practical experience, and respect folk practice and tradition. The clinical positioning of ethnic medicine should consider three factors, i.e., population region, dominant diseases, and clinical demand. We should consider the development of traditional preparations that meet the needs of ethnic regions and encourage the development of new drugs that can be popularized and used nationwide for the dominant diseases of ethnic medicines. Attention should be paid to the problems such as a large number of customary articles or substitutes of ethnic medicinal materials, the phenomena of foreign bodies with the same name and different names for the same substance, the different standards of medicinal materials, and the poor processing standards. The name, processing method, source, medicinal parts, and dosage of ethnic medicinal materials or decoction pieces should be determined, and resources should be carefully evaluated to ensure the safety of medicinal resources and ecology. The preparation of ethnic medicine is mostly in the form of pills, powder, ointment, etc., with simple processing technology. The problems of low-quality stan-dards of some preparations, different prescriptions with the same name, and inconsistent processing technology should be overcome, and the process route and main process parameters should be clarified to lay the foundation for the subsequent empirical research on HUE. In the collection and analysis of the HUE data of ethnic medicine, the core guiding ideology of "patient-centered" should be established, and the experience data of patients should be collected. The problems of weak links existing in the inheritance of ethnic medicine should be solved, and flexible and diverse methods should be adopted. Meanwhile, on the premise of complying with the requirements of the principles of medical ethics, we should respect the religion, culture, and customs of ethnic areas to obtain the key HUE information of ethnic medicine. On the basis of the patient preference information and differences in regional disease epidemiology, population characteristics, and medical practice, whether the HUE conclusions of ethnic medicine can be extrapolated to patients outside the region is evaluated from the aspects of clinical benefits, risk tolerance, risk acceptance, etc. The HUE research on ethnic medicine is carried out in a clear way to guide the research and development of new ethnic medicines.
Humans ; Medicine, Chinese Traditional ; China ; Reference Standards ; Technology ; Drugs, Chinese Herbal/therapeutic use*

AIM: To investigate the protective effect of Modified Taohong Siwu Decoction(MTSD)on hypoxia injury to retinal Müller cells rMC-1.METHODS: Retinal Müller cells rMC-1 were interfered with the MTSD drug-containing serum under hypoxia condition, and were randomly divided into control group(21%O2), hypoxia model group(1%O2), MTSD drug-containing serum low-dose(1%O2+5% medicated serum), medium-dose(1%O2+10% medicated serum)and high-dose(1%O2+15%medicated serum)groups. Cell viability was detected by CCK-8 method, and secretion of vascular endothelial growth factor(VEGF)and pigment epithelium derived factor(PEDF)was detected by ELISA. The protein expressions of p-STAT3, STAT3 and hypoxia-inducible factor-1α(HIF-1α)were detected by Western blot, and the gene expressions of VEGF, PEDF, STAT3 and HIF-1α were detected by real-time polymerase chain reaction(PCR).RESULTS: The viability of rMC-1 cells was significantly inhibited when cultured at 1%O2 for 48h compared with that of control group(P<0.05), while it was improved in both low and medium dose of MTSD groups(P<0.05). The viability of rMC-1 cells in high dose group was not improved in hypoxia condition(P>0.05). The low and medium doses of MTSD could reduce the protein expressions of VEGF in supernatant of rMC-1 cells under hypoxia condition(P<0.05), while the protein expressions of PEDF could not be increased(P>0.05). The above two dose groups down-regulated the protein levels of both p-STAT3 and HIF-1α(P<0.05), and the inhibition effect of low dose group was better than that of medium dose group(P<0.05). The medium dose of MTSD could up-regulate STAT3 protein level after hypoxia culture in rMC-1 cells(P<0.05). The low and medium doses of MTSD significantly down-regulated VEGF gene level(P<0.05)and up-regulated PEDF gene level after hypoxia culture in rMC-1 cells(P<0.05), and the function in the low dose group was superior to that in the medium dose group(P<0.05). The low dose of MTSD could down-regulate STAT3 and HIF-1α gene levels after hypoxia culture in rMC-1 cells(P<0.05).CONCLUSION: Probably by inhibiting the STAT3/HIF-1α pathway, the drug-containing serum of MDST down-regulated the expression of VEGF protein and gene in hypoxia-induced retinal Müller cells, rMC-1, up-regulated the gene expression of PEDF, and alleviated the hypoxia injury to the cells.

Objective:To evaluate the effects of high mobility group protein box 1 (HMGB1) on clinical prognosis of esophagus squamous cell carcinoma (ESCC) patients treated with chemoradiotherapy and the radiosensitivity of xenograft in nude mice.Methods:A total of 90 endoscopic biopsy specimens were obtained from ESCC patients treated with chemoradiotherapy. The expression level of HMGB1 was determined by immunohistochemical staining. High expression level was defined when staining was observed on ≥50% of the tumor cells. All patients were divided into the high expression group ( n=48) and low expression group ( n=42), and their survival information was retrospectively analyzed. Cell transfection was performed with the plasmid carrying human HMGB1-shRNA to knockdown HMGB1 expression in ECA109 cells and xenograft mouse models were established. The tumor volume and mass were calculated after irradiation with a dose of 15 Gy. The cell apoptosis in xenograft tissues were detected. Survival analysis was performed using Kaplan-Meier method. Univariate prognostic analysis was conducted by log-rank test. Intergroup comparison was performed by analysis of variance (ANOVA). Results:The expression level of HMGB1 was significantly associated with gross tumor volume, longest diameter of tumor, T staging and distant metastasis ( χ2=9.663, 5.625, 4.068, 7.146, all P<0.05). In the low expression group, the overall survival (OS) ( χ2=4.826, P=0.028), progression-free survival (PFS) ( χ2=4.390, P=0.036) were longer compared with that in the high expression group. Further analysis of HMGB1-high expression patients showed that the radiation dose and the combination of chemoradiotherapy did not significantly affect the OS or PFS of ESCC patients. We observed that knockdown of HMGB1 slowed the growth rate of xenograft, decreased the tumor volume and increased the apoptosis rate after irradiation. Conclusions:ESCC patients with high expression level of HMGB1 obtain poor prognosis after chemoradiotherapy, which can be enhanced by increasing the sensitivity to radiotherapy and chemotherapy. HMGB1 knockdown can effectively increase the radiosensitivity of xenograft in ESCC nude mice.

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

Human use experience(HUE) is important for the research and development of Chinese medicine. For the sake of more reliable data, the Professional Committee for Clinical Evaluation of Chinese Medicine of Chinese Pharmaceutical Association drafted the Expert Consensus on Human Use Experience Research of Traditional Chinese Medicine. It highlights that the research on HUE should have clear purposes, describe the theoretical basis of traditional Chinese medicine(TCM) for the clinical indications and prescriptions and the clinical value of prescriptions, especially the advantages or characteristics in clinical orientation and target population, evaluate the dosages and number of medicinals of prescriptions, verify the accordance with the preparation process of new Chinese medicine, analyze feasibility of the process for large-scale production and the rationality of the dosage form, and assess the medicinal material resources. Moreover, such research should have reasonable protocol and the collection of clinical data on HUE must comply with medical ethics and avoid conflicts of interest. The collection method should be selected depending on the characteristics of clinical data. Quality control measures should be formulated to ensure the authenticity, accuracy, completeness, reliability, and traceability of clinical data. The definitions on the clinical data should be uniform and clear, and methods should be adopted to avoid bias. The data can be statistically analyzed after the processing. Through the study of HUE, the clinical orientation, target population, commonly used dosage, course of treatment, preliminary efficacy and safety of Chinese medicine prescriptions will be clarified. On this basis, the data on the HUE should be discussed and conclusions will be drawn. Finally, a standardized report will be formed.
Consensus ; Drug Prescriptions ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Reproducibility of Results

Collecting and summarizing human use experience(HUE) data, forming high-quality data and evidences that can be used for evaluation are the key links of HUE research on traditional Chinese medicine(TCM). The collection, collation and summary of human experience data were discussed in this paper. It is pointed out that the collection of HUE should be focus on the source of prescription of new traditional Chinese medicines, and be summarized based on dialectical thinking, experience in medication, characte-ristics of prescription and clinical application. The collected contents include prescription, process, clinical location and applicable population, efficacy data and safety data, etc. The methods include interview, clinical data summary and data mining. When the data formed based on HUE information is used as drug registration information, it is necessary to ensure that the data source is legal and compliant, and the ownership of intellectual property is clear.Data sources should meet the requirements of medical ethics. To avoid conflict of interest, data analysis should be conducted by an independent third party. It is necessary to develop the quality control measures of HUE data to ensure the data traceability, integrity, consistency and accuracy, and avoid data bias.The data of HUE should include the key data such as accurate clinical location and applicable population, recognized clinical efficacy and safety.After the formation of HUE, the statistical analysis plan of empirical data of human use should be formulated. Through strict data processing, statistical analysis and clinical interpretation, HUE can be produced for evaluation.
Data Collection ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Prescriptions ; Quality Control

This article proposes that the research and development of new Chinese medicines should be based on the clinical values of traditional Chinese medicine(TCM), and expounds the multiple clinical values of new Chinese medicines such as therapeutic effects, adjuvant treatment effects, improvement of disease symptoms, improvement of quality of life, prevention of diseases, etc., so as to broaden the clinical indications of new Chinese medicines. It is pointed out that the clinical value of TCM determines the clinical efficacy evaluation method of new Chinese medicines, so as to construct a clinical evaluation system of new Chinese medicines with the characteristics of TCM. It is proposed that the clinical value of new Chinese medicines should be found under the guidance of TCM theo-ry and clinical practice, and the theoretical innovation of TCM should be emphasized. There is no difference in the clinical value of drugs, and the key is to meet the clinical needs of patients. The research and development of new Chinese medicines ignores the theoretical guidance of Chinese medicine, and relying solely on animal experiment data may lead to failure of clinical trials. Different from the individualized treatment of TCM clinical syndrome differentiation, summarizing the core pathogenesis of TCM is the basis for the development of new Chinese medicines. It is necessary to summarize the pathogenesis of the disease under the guidance of TCM theory and encourage the application of modern medical methods to clarify the diagnosis of the disease. In view of the characteristics of new Chinese medicine research and development, it is proposed that the supporting role of human experience should be emphasized, and the technical points of clinical trials of new syndrome-type Chinese medicines should be explained.The use of objective indicators for syndrome evaluation, the selection of appropriate scales, and the formulation of reasonable treatment courses are advocated. During the research and development of new Chinese medicines, it is not only necessary to pay attention to modern medical safety indicators, but also to observe the evolution of TCM syndromes and specific TCM symptoms.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Quality of Life ; Research ; Syndrome