Objective To investigate the effect and mechanism of miglitol on regulating the energy metabolism of brown adipocytes by activating UCP1 and preventing cold injury in mice after cold exposure. Methods Primary brown adipocytes were induced into mature adipocytes, the effect of miglitol on the viability of brown adipocytes was investigated by MTT method, the lipid droplet consumption level of cells after drug administration was investigated by Oil Red O staining technology, and the level of UCP1, a key protein of thermogenesis in brown adipocytes, was detected by Western blotting. The activity of anti-frostbite was investigated in cold exposure at 4 ℃ and −20 ℃. KM mice, which were randomly divided into control group, cold exposure group, miglitol group and all-trans retinoic acid group, and after 7 days of repeated administration, the body surface temperature of mice was detected by infrared thermal imaging system, the anal temperature change was detected by anal thermometer, and the expression levels of UCP1 and PGC1-α in adipose tissue were detected by immunoblotting. Results Compared with the control group, the lipid droplet consumption and UCP1 expression levels in brown adipocytes in the miglitol group were significantly increased. The levels of body surface temperature and rectal temperature increased significantly after cold exposure, and the levels of UCP1 and PGC1α in the brown adipose tissue of mice increased significantly, which indicated that the miglitol could activate the critical proteins UCP1 and PGC1α of the thermogenesis pathway, increase the thermogenesis of mice after cold exposure, and thus improve the effect of cold injury for toe swelling. Conclusion Miglitol could play a role in improving cold injury and body temperature in mice by increasing the level of UCP1 and PGC1α, which are key targets of the thermogenesis pathway to promote the thermogenesis of brown fat.

Objective To investigate the effect of midazolam on neuronal damage in ischemic stroke （IS） rats and its regulatory effect on PTEN-induced putative kinase 1 （PINK1）/E3 ubiquitin ligase （PARKIN） signaling pathway. Methods An IS rat model was established using arterial occlusion method. The rats with successful model were randomly divided into IS group, drug-low, medium, high-dose （drug-L, M, H, 30, 60, 90 mg/kg midazolam） groups, drug-H+autophagy inhibitor 3-MA group （90 mg/kg midazolam+30 mg/kg 3-MA）, and rats with only isolated blood vessels were used as sham surgery groups. Each group received corresponding doses of drugs or physiological saline intervention, and the neurological function scoring, brain histopathology, neuronal apoptosis, ultrastructure, and expression of PINK1, PARKIN, microtubule-associated protein 1 light chain 3 （LC3）, and P62 protein in mitochondria were detected. Results Compared with the IS group, the pathological damage of the drug-L group, drug-M group, and drug-H group was improved, and autophagosomes showed an increasing trend, the expression of PINK1, PARKIN, and LC3 proteins increased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously decreased in a dose-dependent manner （P<0.01 or P<0.001）; compared with the drug-H group, the pathological damage in the drug-H+3-MA group increased and autophagosomes decreased, the expression of PINK1, PARKIN, and LC3 proteins decreased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously increased （P<0.001）. Conclusion Midazolam induced mitochondrial autophagy in IS rats by activating the PINK1/PARKIN signaling pathway, neuronal apoptosis was reduced and neuronal damage were improved in IS rats.

Objective To explore the medication rules of Professor Hua Baojin in the treatment of subsolid pulmonary nodules through retrospective analysis and data mining techniques. Methods The prescriptions of patients with subsolid pulmonary nodules who were diagnosed and treated by Professor Hua Baojin at Guang’anmen Hospital of the Chinese Academy of Chinese Medical Sciences from January 1, 2021 to December 31, 2024 were retrospectively collected. Data were imported into the Ancient and Modern Medical Case Cloud Platform for analysis of drug frequency, four natures and five flavors, meridian tropism, drug association, and hierarchical clustering. Results A total of 455 prescriptions were included, containing 205 kinds of traditional Chinese medicines, with a total frequency of 12048 times. Fifty-seven commonly used drugs were screened out, among which drugs with high frequencies included astragalus membranaceus (raw) and hawthorn fruit (charred). The nature of the drugs was mainly warm, cold, and neutral. The flavor of the drugs was mostly sweet, bitter, and pungent. The meridians they belonged to mainly included the lung, spleen, and liver meridians. Their efficacy was mainly tonifying deficiency, clearing heat, resolving phlegm, and relieving cough and asthma. Association analysis obtained 19 pairs of drug combinations, 21 groups of three-drug combinations, and four groups of four-drug combinations. Hierarchical clustering obtained 10 groups of drug combinations. Conclusion On the basis of the core pathogenesis of subsolid pulmonary nodule, Professor Hua applies the theory of regulating qi and detoxifying; regulating the qi of the liver, spleen, and lung; and detoxifying the toxins of phlegm and blood stasis, providing valuable experience for the clinical treatment of SSN.

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 analyze ethnic differences in mutations of the PIK3CA and TP53 genes among breast cancer patients from the Han, Tibetan, and Hui ethnic groups in Qinghai, China, and their associations with clinicopathological characteristics. Methods A total of 382 breast cancer tissue samples were retrospectively collected from surgical patients (Jan 2020−Dec 2022), comprising 200 Han, 93 Tibetan, and 89 Hui ethnicity. Mutations in PIK3CA (E542K, H1047R, and E545K) and TP53 (R273H and R175H) were detected by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Correlations between mutations and clinicopathological parameters were analyzed. Results Significant differences were observed in pTNM stage, lymph node metastasis, molecular subtypes, and PR status among the three ethnic groups. The overall mutation rate of PIK3CA and TP53 was 48.95%. The PIK3CA-p.E542K mutation rate in Tibetan cohort was significantly higher than those in Han and Hui cohort, whereas the detection rate of the PIK3CA-p.E545K mutation was lower in Tibetan cohort than that in Han cohort. The PIK3CA-p.E542K mutation was associated with an increased risk of lymph node metastasis. The TP53-p.R175H mutation was significantly correlated with advanced pTNM stage, vascular invasion, and triple-negative breast cancer. The PIK3CA-H1047R and E545K mutations were enriched in the luminal A subtype of breast cancer. Conclusion Considerable ethnic disparities exist in breast cancer mutation profiles in Qinghai, with the high-frequency PIK3CA-p.E542K mutation in Tibetan population potentially serving as a region-specific therapeutic target. Mutations are closely linked to tumor aggressiveness and molecular subtypes, highlighting the value of PIK3CA/TP53 mutation detection for early risk stratification and personalized treatment of breast cancer in high-altitude populations.

Objective:To investigate the clinical application effect of double-layer soft tissue(DLST)suture closure technique in patients with mandible medication-related osteonecrosis of the jaw(MRONJ)of early and medium stages resulted in application of anti-bone-resorptive drugs.Methods:Early to me-dium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking Uni-versity School and Hospital of Stomatology from October 2021 to September 2022 were included.Clinical information of the patients were collected,including primary disease,concomitant disease,medication regimen(drug type,duration of medication),MRONJ stage,clinical symptoms,imaging manifestations,etc.During surgery,after using marginal mandibulae resection to remove the necrotic bone,the wound was closed using DLST closure technique.Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique,the pain score and functional status of the patiens were evaluated.Results:This study totally included 13 patients,12 women and 1 man,aged(66.69±13.14)years.Seven patients had osteoporosis,2 had lung cancer,3 had breast cancer and 1 had prostate cancer among their primary diseases;7 had no concomitant diseases,2 had diabetes melli-tus,2 had cardiovascular disease and 1 had dry syndrome.Intravenous zoledronic acid were used in 9 patients,the average duration was(37.7±20.0)months,and other drugs,such as letrozole tablets were taken in 7 patients at the same time;Denosumab injection was used in 3 patients for an average of(10.3±11.9)months;Alendronate sodium tablets were taken in 5 patients for an average of(55.20± 27.20)months,and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 pa-tients.The average post-operative follow-up was 11.9 months(9 to 17 months),and all the 13 patients were cured without complications,such as pus overflow and so forth.The pre-operative score of Karnof-sky performance status(KPS)in the patients was 68.46±14.05,and the post-operative score was 82.31±15.36,and the difference was statistically significant(P＜0.05).The pre-operative score of visual analogue scale(VAS)in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51,and the difference had statistical significance(P＜0.001).Conclusion:The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the man-dible using anti-bone-resorptive drugs alone,and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

Herpes zoster of trigeminal nerve was a common skin disease caused by varicella-zoster virus infection.Simple involvement of the third branch of trigeminal nerve was rare,and so were oral complica-tions such as pulpitis,periodontitis,spontaneous tooth loss,bone necrosis,etc.This article presented a case of herpes zoster on the third branch of the left trigeminal nerve complicated with left mandibular osteonecrosis.We reported the case of a 64-year-old man with sudden pain in the left half of the tongue 1 month ago,and then herpes on the left facial skin appeared following with acute pain.The local hospital diagnosed it as herpes zoster and treated it with external medication.A few days later,he developed gum pain in the left mandibular posterior tooth area.He was admitted to Peking University School and Hospital of Stomatology one week ago with loose and dislodged left posterior tooth accompanied by left mandibular bone surface exposure.Clinical examination showed bilateral symmetry and no obvious restriction of mouth opening.Visible herpes zoster pigmentation and scarring on the left side of the face appeared.The left mandibular posterior tooth was missing,the exposed bone surface was about 1.5 cm x0.8 cm,and the surrounding gingiva was red and swollen,painful under pressure,with no discharge of pus.The re-maining teeth in the mouth were all m degree loosened.Imageological examination showed irregular low-density destruction of the left mandible bone,unclear boundary,and severe resorption of alveolar bone.The patient was diagnosed as left mandibular osteonecrosis.Under general anesthesia,left mandibular le-sion exploration and curettage+left mandibular partial resection+adjacent flap transfer repair were performed.The patient was re-exmained 6 months after surgery,there was no redness,swelling or other abnormality in the gums and the herpes pigmentation on the left face was significantly reduced.Unfortu-nately,the patient had complications of postherpetic neuralgia.This case indicate that clinicians should improve their awareness of jaw necrosis,a serious oral complication of trigeminal zoster,and provide ear-ly treatment.After the inflammation was initially controlled,surgical treatment could be considered to remove the necrotic bone,curettage the inflammatory granulation tissue,and extraction of the focal teeth to avoid further deterioration of the disease.

OBJECTIVE To investigate the monitoring of tacrolimus blood concentration in patients with nephrotic syndrome （NS），and to establish a prediction model for tacrolimus blood concentration. METHODS Data from 509 concentration monitoring sessions of 166 NS patients using tacrolimus were collected from January 1， 2020 to August 31， 2023 in Zhongshan Hospital Affiliated to Xiamen University. The relationship of efficacy and adverse drug reaction（ADR） with blood concentration was analyzed. A multilayer perceptron （MLP） prediction model was established by using the blood concentration monitoring data of 302 times from 109 NS patients with genetic information， and then verified. RESULTS In terms of efficacy， the median blood concentration of tacrolimus in the non-remission group was 2.20 ng/mL， which was significantly lower than that in the partial remission group （4.00 ng/mL， P＜0.001） and the complete remission group （3.60 ng/mL， P＝0.002）. In terms of ADR， the median blood concentration of tacrolimus in the ADR group was 5.01 ng/mL， which was significantly higher than that in the non-ADR group （3.37 ng/mL） （P＝0.001）. According to the subgroup analysis of the receiver operating characteristic curve， when the blood concentration of tacrolimus was ≥6.65 ng/mL， patients were more likely to develop elevated blood creatinine [area under the curve （AUC） was 0.764， P＜0.001）； when the blood concentration of tacrolimus was ≥6.55 ng/mL， patients were more likely to develop blood glucose （AUC＝0.615， P＝ 0.005）. The established MLP prediction model has a loss function of 0.9， with an average absolute error of 0.279 5 ng/mL between the predicted and measured values. The determination coefficient of the validation scatter plot was 0.984， indicating an excellent predictive performance of the model. CONCLUSION Tacrolimus blood concentration has an impact on both efficacy and ADR in NS patients. The use of the MLP model for predicting blood concentration exhibits high accuracy with minimal error between predicted and measured values. The model can be used as an important tool in clinical individualized medication regimens.

Primary hyperparathyroidism is a disease with a large potential population. Some cases of primary hyperparathyroidism are non-primary, preventable and curable at early stage, requiring long-term follow-up after surgery. Therefore, all-round and full-cycle management are necessary for primary hyperparathyroidism, which involves an enhancing focus on etiological prevention, early detection, prompt diagnosis, timely intervention, multi-disciplinary standardized diagnosis and treatment, and postoperative scientific management. Meanwhile, implementing a "12+5+1" multidisciplinary joint diagnosis and treatment model, along with a two-way referral model, to achieve the transition from a disease-oriented diagnostic and treatment model to a patient-oriented, all-round and full-cycle interdisciplinary management model. This management can reduce the incidence and recurrence rate of primary hyperparathyroidism, and related osteoporosis or osteopenia, fractures, nephrolithiasis, metastatic vascular calcification, and systemic abnormal migratory calcium deposits, improve the overall quality of life and prognosis of patients.

The incidence of parathyroid hyperfunction is high and its clinical manifestations are diverse. Some patients develop chest tightness and palpitations as the main discomfort, which may be caused by the hypocalcemia and hypercalcemia related to negative calcium balance and parathyroid hyperfunction. We report a case of 53 years old male with parathyroid hyperfunction who was diagnosed with osteoporosis before and received conventional regular supplementation of vitamin D and calcium supplements. However, his condition worsened and he developed chest tightness and palpitation. After 1 month of sufficient supplementation of calcium, the symptoms of chest tightness and palpitation disappeared completely. Then we continued to provide the patients enough vitamin D and calcium supplementation actively. After 1 year of follow-up, the patient's condition was stable. His discomfort of chest tightness and palpitation never recurred, and all the bone metabolism indicators returned to normal.