Objective To investigate the clinicopathological factors associated with pathological complete response(pCR)of axillary metastatic lymph nodes in breast cancer patients after neoadjuvant chemotherapy(NAC),and to analyze the postoperative survival.Methods A total of 116 patients with breast cancer with axillary lymph node metastasis were collected from Jiaxing Hospital of TCM,Jiaxing Maternity and Child Health Care Hospital and The First Hospital of Jiaxing.Univariate analysis was used to analyze the relationship between clinicopathological factors and the pCR of axillary lymph node metastasis in breast cancer after NAC.Binary Logistic regression was used to analyze the independent predictors of the pCR of axillary lymph node metastasis in breast cancer after NAC.Kaplan-Meier survival curve was used to analyze the disease-free survival rate and overall survival rate of patients with and non-pCR of axillary metastatic lymph nodes.Results Among 116 patients,52 cases of axillary metastatic lymph nodes achieved pCR after NAC,accounting for 44.83%.Univariate analysis showed that age,vascular invasion,pCR of primary breast tumor,the difference of Ki67 before and after NAC,NAC regimen,and the efficacy of NAC were statistically significant between breast cancer patients with pCR and those non-pCR(P<0.05).Binary Logistic regression analysis showed that age,vascular invasion and pCR of primary breast tumor were independent predictors of pCR of axillary metastatic lymph nodes(P<0.05).The 5-year disease-free survival rate(80.40%vs.54.60%)and overall survival rate(90.4%vs.70.10%)of patients with pCR and non-pCR of axillary metastatic lymph nodes were compared.Conclusion Some breast cancer patients with axillary lymph node metastasis can reach pCR in lymph nodes after NAC.Analyzing the correlation between clinical pathological factors and pCR of axillary metastatic lymph nodes after NAC,it was found that pCR of axillary metastatic lymph nodes after NAC is related to age≤50 years old,no vascular infiltration,and primary breast tumor pCR.At the same time,it was found that patients with axillary metastatic lymph node pCR had a better prognosis than those with non-pCR.

Blood and lymphatic vessels are absent from the normal cornea.Pathological stimulation such as corneal in-fection,chemical burns and transplantation rejection can disrupt the balance between pro-and anti-lymphangiogenesis fac-tors,causing lymphatic vessels to extend from the corneal limbus to the central cornea.Corneal lymphangiogenesis is closely related to various regulatory factors and cellular signaling pathways.Further study and elucidation of the mechanism of corneal lymphangiogenesis will open up new directions for treating corneal transplantation rejection,inflammatory disea-ses,dry eyes and tumor metastasis.This review concludes the endogenous regulatory factors of corneal lymphangiogenesis and therapeutic strategies for its related ocular surface diseases.

Objective To analyze the effectiveness and safety of bisphosphonates in the treatment of pa-tients with calcification defense.Methods PubMed,Embase databases,CNKI and Wanfang were searched to collect the case reports and clinical studies of bisphosphonates for calcification defense.Then,the relevant infor-mation of patients was extracted for statistical analysis.Results A total of 18 case reports were selected involving 20 patients.Thirteen patients(65.0％)were treated with pamidronate,four(20.0％)were treated with etidr-onate,two(10.0％)were treated with alendronate,and one(5.0％)was treated with zoledronic acid.Thirteen patients(65.0％)recovered completely,the recovery time of whom ranged from half month to nine months.The tolerance of bisphosphonates in most patients(90.0％)was good,while one patient who did not tolerate pamidr-onate recovered after the frequency of administration was adjusted and one patient with high dosage of etidronate returned to normal after the discontinuation of the usage.Conclusions Bisphosphonates,an inhibitor of bone resorption,is effective and safe in the treatment of patients with calcification defense.

Objective To construct and identify a patient-derived organoid model,and to investigate the sensitivity of chemotherapy drugs using this model.Methods Pancreatic cancer cells were obtained from the surgical specimens of two female patients with a confirmed diagnosis of pancreatic cancer after tumor tissue digestion,and then the cells were inoculated into a culture dish using matrigel for three-dimensional culture.Paraffin sections were prepared for HE staining and immunohistochemical staining and were compared with the parent tumor tissue to determine whether the histopathological features of the tumor in vivo were preserved.The pancreatic cancer organoids were treated with seven chemotherapy drugs at different concentrations;Cell Titer-Glo?3D reagent was used to measure cell viability,and the results of drug sensitivity were analyzed.Results Two patient-derived pancreatic cancer organoids were successfully constructed,and HE staining and immunohistochemical staining showed that the pancreatic cancer organoids had consistent histopathological features with the tumors of the corresponding patient.Both pancreatic cancer organoids were more sensitive to gemcitabine monotherapy and the combination of oxaliplatin+SN38+fluorouracil,and patient 1 was more sensitive than patient 2.There were individual differences in the response to drugs between the organoids from different patients.Conclusion The pancreatic cancer organoid model successfully constructed in this study can reflect the histological classification of parent pancreatic tumors and can be used for in vitro chemotherapy drug sensitivity test,which is expected to provide a reference for clinical medication.

This article introduced Professor Wang Xingkuan's academic thoughts and clinical experience in diagnosing and treating burning mouth syndrome(BMS)in perimenopausal women based on the theory of"yin injury and internal dryness".Professor Wang advocates the principle of"treating the root cause of the disease and harmonizing multiple organs".Starting from the unique physiological characteristics of perimenopausal women,he believes that the BMS in perimenopausal women should be attributed to the kidneys,liver,heart,and small intestine.The fundamental cause of the disease is the deficiency of kidney essence and the gradual decline of liver blood,and the key to the onset is the dryness of the kidney,liver,heart,and small intestine.In treatment,the overall strategy is to take"yin injury and internal dryness"as the main guideline,focusing on the liver and kidney,with nourishing and replenishing the liver and kidney as the main approach and clearing heat and moistening as auxiliary methods.The basic formula for treating BMS is a combination of Erdong Decoction and Baihe Dihuang Decoction,which has shown significant clinical efficacy.

OBJECTIVE: To investigate the feasibility of MRI three-dimensional (3D) reconstruction model in quantifying glenoid bone defect by comparing with CT 3D reconstruction model measurement. METHODS: Forty patients with shoulder anterior dislocation who met the selection criteria between December 2021 and December 2022 were admitted as study participants. There were 34 males and 6 females with an average age of 24.8 years (range, 19-32 years). The injury caused by sports injury in 29 cases and collision injury in 6 cases, and 5 cases had no obvious inducement. The time from injury to admission ranged from 4 to 72 months (mean, 28.5 months). CT and MRI were performed on the patients' shoulder joints, and a semi-automatic segmentation of the images was done with 3D slicer software to construct a glenoid model. The length of the glenoid bone defect was measured on the models by 2 physicians. The intra-group correlation coefficient ( ICC) was used to evaluate the consistency between the 2 physicians, and Bland-Altman plots were constructed to evaluate the consistency between the 2 methods. RESULTS: The length of the glenoid bone defects measured on MRI 3D reconstruction model was (3.83±1.36) mm/4.00 (0.58, 6.13) mm for physician 1 and (3.91±1.20) mm/3.86 (1.39, 5.96) mm for physician 2. The length of the glenoid bone defects measured on CT 3D reconstruction model was (3.81±1.38) mm/3.80 (0.60, 6.02) mm for physician 1 and (3.99±1.19) mm/4.00 (1.68, 6.38) mm for physician 2. ICC and Bland-Altman plot analysis showed good consistency. The ICC between the 2 physicians based on MRI and CT 3D reconstruction model measurements were 0.73 [95% CI (0.54, 0.85)] and 0.80 [95% CI (0.65, 0.89)], respectively. The 95% CI of the difference between the two measurements of physicians 1 and 2 were (-0.46, 0.49) and (-0.68, 0.53), respectively. CONCLUSION The measurement of glenoid bone defect based on MRI 3D reconstruction model is consistent with that based on CT 3D reconstruction model. MRI can be used instead of CT to measure glenoid bone defects in clinic, and the soft tissue of shoulder joint can be observed comprehensively while reducing radiation.
Male ; Female ; Humans ; Young Adult ; Adult ; Imaging, Three-Dimensional/methods* ; Tomography, X-Ray Computed/methods* ; Joint Instability ; Shoulder Joint/diagnostic imaging* ; Shoulder Dislocation ; Magnetic Resonance Imaging/methods*

Transthyretin(TTR) protein is a tetramer protein, synthesized mainly by the liver. TTR can be misfolded and deposited as amyloid fibrilae and deposited in the myocardial interstroma leading to transthyroxin amyloidosis cardiomyopathy (ATTR-CM). ATTR-CM was included in China's First List of Rare Diseases. Therapeutic strategies for ATTR-CM include blocking TTR synthesis in the liver, stabilizing TTR tetramers and destroying TTR fibra. Small molecule drugs such as tafamidis and diflunisal offer new treatment options for patients. Chlorobenzolic acid became the first drug approved by the U.S. Food and Drug Administration for the treatment of ATTR-CM. Small interfering RNA(siRNA)patisiran and antisense oligonucleotide (ASO)inotersen block TTR expression in the liver and have been approved for the treatment of ATTR variant polyneuropathy (ATTRv-PN)and are in phase Ⅲ trials for the treatment of ATTR-CM. Other siRNA drugs, vutrisiran, and ASO, eplontersen, are being evaluated for clinical efficacy. This article reviews the development of RNA-targeted therapeutics and gene-editing drugs using CRISPR-Cas9.

OBJECTIVE: Immunotherapy has brought significant clinical benefits to a subset of patients, but has thus far been disappointing in the treatment of immunologically "cold" tumors. Existing biomarkers that can precisely identify these populations are insufficient. In this context, a potential cold tumor microenvironment (TME) marker FARSB was investigated to reveal its impact on TME and patients' response to immunotherapy across pan-cancer. METHODS: The expression levels and mutational landscape of FARSB in pan-cancer were investigated. Kaplan-Meier and univariate Cox regression analyses were applied to analyze the prognostic significance of FARSB. Pathways affected by FARSB were investigated by gene set enrichment and variation analysis. The relationship between FARSB expression and immune infiltration was examined using the TIMER2 and R packages. Single-cell RNA sequencing (scRNA-seq) data of several cancer types from GSE72056, GSE131907, GSE132465, GSE125449 and PMID32561858 were analyzed to validate the impact of FARSB on the TME. The predictive effect of FARSB on immunotherapy efficacy was explored in 3 immune checkpoint inhibitors (ICIs)- treated cohorts (PMID32472114, GSE176307, and Riaz2017). RESULTS: FARSB expression was significantly higher in 25 tumor tissues than in normal tissues and was associated with poor prognosis in almost all tumor types. FARSB expression exhibited a strong association with several DNA damage repair pathways and was significantly associated with TP53 mutation in lung adenocarcinoma (P < 0.0001, OR=2.25). FARSB characterized a typical immune desert TME and correlated with impaired expression of chemokines and chemokines receptors. Large-scale scRNA-seq analysis confirmed the immunosuppressive role of FARSB and revealed that FARSB potentially shapes the cold TME by impeding intercellular interactions. In 3 ICI-treated cohorts, FARSB demonstrated predictive value for immunotherapy. CONCLUSION This study provides a pan-cancer landscape of the FARSB gene by integrated single-cell and bulk DNA sequencing analysis and elucidates its biological function to promote DNA damage repair and construct the immune desert TME, suggesting the potential value of FARSB as a novel marker for stratifying patients with poor immunotherapeutic benefits and "cold" TME.
Humans ; Tumor Microenvironment ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Sequence Analysis, RNA

Remote pharmaceutical care refers to the process that pharmacists provide pharmaceutical care to patients remotely through information technology. Remote pharmaceutical care in China starts late and develops slowly. Therefore ，this paper discusses the pharmaceutical care modes that pharmacists at home and abroad can provide under the remote mode by collecting literature. The results show that foreign remote pharmaceutical care starts early and is relatively mature. The service mainly included remote follow-up and intervention ，24-hour online prescription and order review ，24-hour online drug reorganization ，and guidance on rational drug use in remote areas or community hospitals. The service population covers patients with cardiovascular disease ， diabetes，asthma，AIDS and so on. Some hospitals have established an integrated pharmaceutical care system of “Internet+Medical Consortium”in China ，with which pharmacists can provide patients with pharmaceutical care such as remote follow-up and intervention，drug consultation and so on. With the promotion of telemedicine ，domestic pharmacists can gradually expand the scope of services ，expand pharmaceutical services such as remote consultation and remote popular science push ，and realize the sharing of high-quality pharmaceutical care for the whole people.

Objective:To evaluate the relationship between the euchromatic histone-lysine N-methyltransferase (G9a) and sodium-dependent activation of potassium channel (Slack) in the dorsal root ganglia (DRG) of rats with neuropathic pain (NP).Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 1 month, weighing 100-120 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (S group), vector plus sham operation group (VS group), vector plus NP group (VN group), and G9a CRISPR/Cas9 knockout plus NP group (GN group). Sham operation was performed at the age of 2 months in group S. In group VS, AAV5 1 μl was microinjected into L 4 and L 5 DRG at the age of 1 month, and sham operation was performed at the age of 2 months.In VN group and GN group, AAV5 and G9a CRISPR/Cas9 knockout plasmid 1 μl were microinjected into L 4 and L 5 DRG at the age of 1 month, and NP model was established by spinal nerve ligation (SNL) at the age of 2 months.Six rats in each group were selected to measure the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) before microinjection (T 0), before SNL (T 1), and at 3, 5 and 7 days after SNL (T 2-4). The animals were sacrificed after the last behavioral testing, the DRGs of lumbar segment (L 4, 5) were removed for determination of the expression of G9a, dimethylation of histone H3 at lysine 9(H3K9me2) and Slack (by Western blot). At 7 days after establishing the model, 6 rats from each group were selected to culture the primary DRG neurons.The frequency and amplitude of Slack current in DRG neurons and miniature excitatory post-synaptic currents (mEPSCs) in the spinal dorsal horn were measured by whole-cell patch-clamp technique. Results:Compared with group S, the TWL was significantly shortened and the MWT was decreased at T 2-4, the expression of G9a and H3K9me2 in the spinal dorsal horn was up-regulated, the expression of Slack was down-regulated, the amplitude and frequency of Slack currents in DRG neurons were decreased, and the frequency of mEPSCs was increased in group VN ( P<0.05), and no significant change was found in the parameters mentioned above in group VS ( P>0.05). Compared with group VN, the TWL was significantly prolonged and the MWT was increased at T 2-4, the expression of G9a and H3K9me2 in the spinal dorsal horn was down-regulated, the expression of Slack was up-regulated, the amplitude and frequency of Slack currents in DRG neurons were increased, and the frequency of mEPSCs was decreased in group GN ( P<0.05). Conclusion:The mechanism of NP is related to up-regulating the expression of G9a in DRG, thus inhibiting the expression and opening of Slack channels in rats.