This article systematically reviews the current research status as well as diagnosis and treatment strategies of traditional Chinese medicine （TCM） for gastroesophageal reflux disease （GERD）. Studies demonstrate that TCM， based on the "disease-syndrome combination" approach， exhibits multi-target advantages in alleviating symptoms of various GERD subtypes， promoting mucosal repair， regulating emotions， and facilitating the reduction of western medication. To address clinical challenges such as symptom overlap and limited therapeutic efficacy， strategies have been proposed including "treating different diseases with the same method" and integrated regulation based on viscera correlation. Future efforts should focus on elucidating the mechanisms of compound prescriptions， promoting TCM drug development under the "three-combination" evaluation framework that integrates TCM theory， human experience and clinical trial evidence， and optimizing integrated traditional and western medicine models to enhance GERD management.

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Objective:To observe the clinical efficacy and safety of Jianpi Bushen Jiedu Prescription combined with 5-fluorouracil (5-FU)-based chemotherapy and targeted therapy for the treatment of advanced colorectal cancer patients with liver and kidney yin deficiency combined with spleen deficiency pattern.Methods:A randomized controlled trial was conducted. A total of 72 hospitalized patients with advanced colorectal cancer treated at the Department of Oncology, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from October 2022 to January 2024 were enrolled as study subjects. Using a random number table method, they were allocated into two groups, with 36 patients in each group. The control group received the mFOLFOX6/FOLFIRI combined with bevacizumab regimen, while the treatment group was administered additional oral Jianpi Bushen Jiedu Prescription on the basis of the control group. Two weeks was a cycle in both groups, with a total of 6 cycles of treatment. Serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) were detected using electrochemiluminescence; the Karnofsky Performance Status (KPS) scale was utilized to evaluate patients' functional status; vital signs were continuously monitored, and adverse reactions were recorded. The short-term efficacy and TCM syndrome efficacy of patients were evaluated.Results:The treatment group demonstrated higher objective response rate (ORR) [31.25% (10/32) vs. 21.88% (7/32), χ2=0.72] and disease control rate (DCR) [84.38% (27/32) vs. 71.88% (23/32), χ2=1.46] compared to the control group, without statistical significance ( P>0.05). Post-treatment levels of CEA [4.09 (3.31,8.57) μg/L vs. 10.07 (4.55,22.35) μg/L, Z=-2.10] and CA72-4 [4.54 (2.04,10.99) mU/L vs. 9.48 (4.34,18.95) mU/L, Z=-2.52] in the treatment group were significantly lower than those in the control group ( P<0.05). The total effective rate of TCM syndrome was significantly higher in the treatment group [78.13% (25/32)] compared with the control group [50.00% (16/32)], with statistical significance ( χ2=5.50, P=0.019). Post-treatment KPS scores in the treatment group [80.0 (80.0, 80.0) vs. 70.0 (62.5, 80.0), Z=-2.76] were significantly higher compared with the control group ( P<0.01). During the treatment period, the treatment group showed statistical significance compared with the control group in the incidence of hemoglobin decrease ( χ2=4.66), leukopenia decrease ( χ2=4.27), and peripheral neuropathy ( χ2=3.93), with statistical significance ( P<0.05). Conclusion:The addition of Jianpi Bushen Jiedu Prescription to 5-FU-based chemotherapy combined with targeted therapy demonstrates significant clinical benefits in advanced colorectal cancer patients, including reducing tumor marker levels, alleviating clinical symptoms, improving quality of life, and mitigating treatment-related toxicities, with a good safety.

ObjectiveTo collate and compare the characteristics and differences in the methods for constructing animal models of different subtypes of gastroesophageal reflux disease （GERD） based on literature， providing a reference for researchers in this field regarding animal model construction. MethodsExperimental studies related to GERD including reflux esophagitis （RE）， nonerosive reflux disease （NERD） and Barrett's esophagus （BE） model construction from January 1， 2014 to January 27， 2024， were retrieved from databases such as CNKI， Wanfang， VIP， Web of Science， and Pubmed. Information on animal strains， genders， modeling methods including disease-syndrome combination models， modeling cycles were extracted； for studies with model evaluation， the methods of model evaluation were also extracted； then analyzing all those information. ResultsA total of 182 articles were included. SD rats were most frequently selected when inducing animal models of RE （88/148， 59.46%） and NERD （9/14， 64.29%）. For BE， C57BL/6 mice were most commonly used （11/20， 55.00%）. Male animals （RE： 111/135， 82.22%； NERD： 11/14， 78.57%； BE： 10/12， 83.33%） were the most common gender among the three subtypes. The key to constructing RE animal models lies in structural damage to the esophageal mucosal layer， gastric content reflux， or mixed reflux， among which forestomach ligation + incomplete pylorus ligation （42/158， 26.58%） was the most common modeling method； the key to constructing NERD animal models lies in micro-inflammation of the esophageal mucosa， visceral hypersensitivity， and emotional problems， and intraperitoneal injection of a mixed suspension of ovalbumin and aluminum hydroxide combined with acid perfusion in the lower esophagus （8/14， 57.14%） was the most common modeling method； the key to constructing BE animal models lies in long-term inflammatory stimulation of the esophageal mucosa and bile acid reflux， and constructing interleukin 2-interleukin 1β transgenic mice （7/25， 28.00%） was the most common modeling method. Adverse psychological stress was the most common method for inducing liver depression. ConclusionsThe construction key principles and methodologies for RE， NERD， and BE animal models exhibit significant differences. Researchers should select appropriate models based on subtype characteristics （e.g.， RE focusing on structural damage， NERD emphasizing visceral hypersensitivity）. Current studies show insufficient exploration of traditional Chinese medicine disease-syndrome combination models. Future research needs to optimize syndrome modeling approaches （e.g.， composite etiology simulation） and establish integrated Chinese-Western medicine evaluation systems to better support mechanistic investigations of traditional Chinese medicine.

This article retrospectively analyzed the involvement of clinical pharmacists in the treatment process and implementation of pharmacological supervision in a patient with septic arthritis secondary to tophi ulceration.The patient was admitted to the hospital and the emergency debridement and tophi removal were performed.Piperacillin-tazobactam,imipenem cilastatin,levofloxacin,linezolid,and vancomycin were given successively,and multiple debridement and drainage were performed,but the patient remained febrile and had recurrent infection indicators.According to the relevant guidelines and evidence-based evidence,combined with the patient's infection indicators,pathogen results and creatinine clearance rate,the clinical pharmacists recommended stopping vancomycin and changing to cefazolin,and the clinicians adopted it.After that,the patient's inflammatory indicators gradually decreased,and the body temperature stabilized.After 28 days of piperacillin-tazobactam administration,the patient developed a reduction in white blood cell count(2.34×109·L-1)and potassium(2.98 mmol·L-1).The pharmacist recommended prompt discontinuation of the drug,and the patient's white blood cell count and potassium gradually recovered.Eventually,after anti-infective treatment and surgical intervention,the patient was discharged with closure of the infected foci,conversion of multiple blood cultures to negative,and stabilisation of body temperature and renal function.This case reflects the role of clinical pharmacists in the management of drug treatment of critically ill patients,and may provide practical experience and reference for clinical treatment of such cases.

This article retrospectively analyzed the involvement of clinical pharmacists in the treatment process and implementation of pharmacological supervision in a patient with septic arthritis secondary to tophi ulceration.The patient was admitted to the hospital and the emergency debridement and tophi removal were performed.Piperacillin-tazobactam,imipenem cilastatin,levofloxacin,linezolid,and vancomycin were given successively,and multiple debridement and drainage were performed,but the patient remained febrile and had recurrent infection indicators.According to the relevant guidelines and evidence-based evidence,combined with the patient's infection indicators,pathogen results and creatinine clearance rate,the clinical pharmacists recommended stopping vancomycin and changing to cefazolin,and the clinicians adopted it.After that,the patient's inflammatory indicators gradually decreased,and the body temperature stabilized.After 28 days of piperacillin-tazobactam administration,the patient developed a reduction in white blood cell count(2.34×109·L-1)and potassium(2.98 mmol·L-1).The pharmacist recommended prompt discontinuation of the drug,and the patient's white blood cell count and potassium gradually recovered.Eventually,after anti-infective treatment and surgical intervention,the patient was discharged with closure of the infected foci,conversion of multiple blood cultures to negative,and stabilisation of body temperature and renal function.This case reflects the role of clinical pharmacists in the management of drug treatment of critically ill patients,and may provide practical experience and reference for clinical treatment of such cases.

Objective:To evaluate the short-term efficacy and safety of 3D printing patient-matched artificial vertebral body in clinical research and application.Methods:A total of 12 patients with spinal tumors were enrolled 7 males (58.33%) and 5 females (41.67%), aged from 18 to 65 years old in The First Affiliated Hospital of Air Force military Medical University (hereinafter referred to as Xijing Hospital) and Peking University people's Hospital from September 2021 to July 2022. The spinal vertebra defect were restored by using 3D printing patient-matched artificial vertebral body after tumor resection. All patients who accepted TES and 3D printing patient-matched artificial vertebral body implantation were included according to the inclusion and exclusion criteria. The bone interface fusion was evaluated by the imaging fusion criteria of Brantigan and Steffee at 3 and 6 months after operation, the curative effect was evaluated by comparing Japanese Orthopaedic Association (JOA) score at 3 and 6 months after operation, visual analogue scale (VAS) 3 months after operation and intervertebral height at 3 and 6 months after operation with those before operation, and the safety was evaluated by adverse event recording.Results:All 12 patients completed the operation successfully, and the operation sites were thoracic vertebrae in 6 cases (50%), thoracolumbar in 3 cases (25%) and lumbar vertebrae in 3 cases (25%). All patients were followed up. The mean follow-up time was 23.92±3.23 months (range, 19-29 months). No tumor recurrence or metastasis was observed during this period. All patients were followed up at 15 days, 3 months and 6 months after operation. During the 6-month follow-up, X ray results showed that interface of bone and the vertebral body were fused in all of the 12 patients, and the effective rate of fusion was 100%. The 95% confidence interval is calculated to be (75.6%-100%). Six months after operation, the improvement rate of JOA score was excellent in 10 cases, good in 1 case, poor in 1 case, and the excellent and good rate was 91.66%. The preoperative VAS score was 4.08 ±2.47, and during the 3-month follow-up, the VAS score was improved to 1.83 ±1.59. Compared with the preoperative VAS score, the difference was statistically significant ( t=2.635, P=0.023). The intervertebral height before operation, 15 days after operation, 3 months after operation and 6 months after operation were 32.75 (25.94, 68.20), 41.09 (30.55, 70.20), 40.70 (30.23, 67.83) and 40.74 (30.23, 67.08), respectively, and there was no statistically significant difference (χ 2=0.768, P=0.857). No implant-related adverse events occurred after operation. Conclusion:The 3D printing patient-matched artificial vertebral body used in this study has satisfactory short-term efficacy and safety in the reconstruction of spinal stability after spinal tumor resection.

The tendon-bone interface is where the tendons or ligaments are connected with the bones. A spectrum of injuries may happen to the "soft-to-hard" tissue interface, including those to the rotator cuff-bone and cruciate ligament-bone interfaces, which are often precipitated by a combination of degenerative changes on the tendon-bone interface and acute or chronic injuries, thus severely impairing the patients′ motor function. In recent years, with the deepening of the interdisciplinary researches in biomechanics, mechanobiology, and sports medicine, the role of mechanical factors in the repair of tendon-bone interface injuries has attracted more and more attention and becomes a focus of the edge-cutting researches on the tendon-bone interface injuries. To this end, the authors proposed the concept of "tendon-bone interface mechanomedicine" based on an overview of the relevant researches at home and abroad. The mechanical properties of the tendon-bone interface and the effects of mechanical stimuli on its biological behavior were elucidated from the four aspects: biomechanics, mechanobiology, mechanodiagnostics, and mechanotherapy, aiming to explore the diagnostic and therapeutic strategies for tendon-bone interface injuries from the angle of mechanics and provide new perspectives and methodologies for the field of tendon-bone interface injury repair.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC₅₀ > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

Objective:The residual cancer burden (RCB) evaluation system was used to analyze the influencing factors of the efficacy of neoadjuvant therapy in breast cancer, and to explore the prognostic value of RCB evaluation in neoadjuvant therapy.Methods:Clinicopathologic data and postoperative RCB grading of 364 breast cancer patients who underwent neoadjuvant therapy in Renmin Hospital of Wuhan University from Nov. 2019 to Nov. 2022 were collected. Chi-square test was used to analyze the relationship between RCB grading and clinicopathological parameters, and Spearman’s rank correlation analysis was performed to evaluate the correlation between RCB grading and clinicopathological characteristics. Factors influencing pathologic complete response (pCR) were analyzed by Logistic regression. Kaplan-Meier survival analysis and log-rank test were used to evaluate cumulative survival.Results:Among the 364 patients who underwent neoadjuvant therapy, 129 cases of RCB grade 0 and 235 cases of RCB gradeⅠ-Ⅲ (including 46 cases of RCB gradeⅠ, 109 cases of RCB grade Ⅱ and 80 cases of RCB grade Ⅲ) were obtained after surgery. Histological classification ( χ 2=21.757, P=0.000), estrogen receptor (ER) ( χ 2=52.837, P=0.000), progesterone receptor (PR) ( χ 2=55.658, P=0.000), human epidermal growth factor receptor-2 (HER2) ( χ2=89.040, P=0.000), Ki67 expression ( χ2=12.927, P=0.005), molecular typing ( χ 2=80.793, P=0.000) and preoperative lymph node status ( χ 2=25.764, P=0.000) were all associated with postoperative RCB grading. Further correlation analysis showed that histological grade ( r=-0.229, P=0.000), HER2 expression ( r=-0.465, P=0.000) and Ki67 expression ( r=-0.179, P=0.000) were negatively correlated with RCB grading, while ER ( r=0.352, P=0.000), PR ( r=0.379, P=0.000) and lymph node metastasis ( r=0.214, P=0.000) were positively correlated with RCB grading. Logistic regression analysis showed that high histological grade, negative expression of ER, PR and AR, positive expression of HER2, high proliferation index of Ki67 and no lymph node metastasis were favorable factors for postoperative pCR, and PR, AR and HER2 were independent predictors of postoperative pCR. Kaplan-Meier survival analysis showed significant differences in postoperative cumulative survival among patients with different RCB grades ( P=0.004) . Conclusions:Postoperative RCB grading of breast cancer is closely related to many clinicopathological features before neoadjuvant therapy and survival prognosis. Clinicopathological factors closely related to RCB grading are also important influencing factors affecting the pCR of patients with neoadjuvant therapy. Therefors, RCB grading has a high prognostic value.