ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

Pathological diagnosis is vital in medicine. Developing and implementing high-quality pathology guidelines and consensus can enhance disease diagnosis accuracy and reduce unnecessary misdiagnosis and missed diagnoses. This article will cover the current status of pathology guidelines and consensus, methods for high-quality development, and the distinctions between them. Additionally, it will provide thoughts and suggestions for promoting their development in China.

The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.

Objective:To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression.Methods:The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected.Results:The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive ( P<0.001), Ki-67 index below 35% ( P<0.001), well or moderate differentiation ( P<0.001) and over the age of 50 ( P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions:The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.

Objective:To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer.Methods:A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate.Results:Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side ( P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion:For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

Objective:To analyze the expression of meiotic recombination 11 homolog A（MRE11A）in T lymphocytes of children with sepsis，and to explore the effect of MRE11A on the function of T lymphocytes in sepsis.Methods:Twenty-four children with sepsis hospitalized in PICU at the First Affiliated Hospital of Guangxi Medical University from December 2021 to April 2022 were selected as sepsis group.During the same period,24 healthy children who underwent outpatient physical examination in our hospital were selected as control group.The gender and age of two groups were collected,and the duration of invasive mechanical ventilation,laboratory examination index and hospitalization time were collected in sepsis group.The peripheral blood samples of sepsis group were collected within 24 hours of admission to PICU,and peripheral blood samples of control group were collected during the study period.Flow cytometry was used to detect the cytoplasmic MRE11A of peripheral blood T lymphocytes in two groups,and the proportion as well as expression of MRE11A positive cells between two groups were compared (expressed by mean fluorescence intensity) .Results:There were 24 cases in sepsis group,including 11 males and 13 females,with a median age of 32.50 (19.00,132.75) months.There were 24 cases in control group,including 14 males and 10 females,with a median age of 57.50 (33.75,102.25) months.There were no significant differences in gender and age between two groups (all P>0.05).The proportion of MRE11A +CD4 +T lymphocytes in sepsis group was lower than that in control group[3.59（2.29，8.87）% vs.99.90（99.03，100.00）%， Z=-5.961， P<0.001 ].The expression of MRE11A in CD4 +T lymphocytes in sepsis group was lower than that in control group[1 663.00（1 557.00，1 777.00）vs.5 689.00（4 415.25，9 567.00）， Z=-5.939， P<0.001].The proportion of MRE11A +CD8 +T lymphocytes in sepsis group was lower than that in control group[3.85（1.87，9.58）% vs.92.15（76.70，96.40）%， Z=-5.856， P<0.001].The expression of MRE11A in CD8 + T lymphocytes in sepsis group was lower than that in control group[1 921.50（1 680.00，2 217.00）vs.4 165.00（2 894.00，9 122.00）， Z=-5.083， P<0.001]. Conclusion:The expression level of MRE11A in the cytoplasm of T lymphocytes in children with sepsis was decreased,which may affect the function of T lymphocytes.

Objective To investigate the clinical effect of anterolateral mini-incision assisted reduction with InterTan intramedullary nail in the treatment of elderly refractory femoral intertrochanteric fractures to provide reference for clinical treatment.Methods Fifty-eight elderly patients with femoral intertrochanteric fractures admitted and treated in this hospital from August 2020 to April 2023 were selected as the study sub-jects and divided into the observation group and control group accroding to the operation program,29 cases in each group.The observation adopted the anterolateral mini-incision assisted reduction with InterTan intramed-ullary nail,in which there were 6 males and 23 females,the age averaged(86.14±4.98)years old.The control group adopted the closed reduction InterTan intramedullary nail therapy,in which there were 8 males and 21 females,the age averaged(86.33±5.09)years old.The intraoperative bleeding volume,hospitalization dura-tion,incidence rate of fracture related complications,operation time,postoperative fracture reduction quality,postoperative medial cortical support type and postoperative hip joint Harris score were compared between the two groups.Results The two groups obtained the followed up,the follow up time was 6-12 months,with an average(11.45±1.59)months.There were no statistically significant differences in the intraoperative bleed-ing volume,hospitalization duration,incidence rate of fracture related complications between two groups(P＞0.05).The operation time in the observation group was(88.79±29.58)min,which in the control group was(70.66±24.47)min,and there was statistical difference between the two groups(P＜0.05).The excellent and good rate of fracture reduction quality in the observation group was 100.00％,which in the control group was 75.86％,and the difference between the two groups had statistical significance(P＜0.05).The propor-tion of positive and neutral medial cortical support in the observation group was 96.55％,which in control group was 72.41％,and the difference between the two groups was statistically significant(P＜0.05).The hip Harris score in the observation group was(76.33±12.71)points,which in the control group was(68.39±13.17)points,and the difference between the two groups was statistically significant(P＜0.05).Conclusion The eld-erly patients with refractory femoral intertrochanteric fracture are often combined with multiple underlying diseases,and the surgical risk is extremely high.Adopting anterolateral mini-incision assisted reduction with InterTan intramedullary nail fixation treatment could achieve the satisfactory reduction and fixation without increasing obvious trauma and the effect is reliable.

Objective:To explore the changes in serum levels of miR-499 and miR-362 in patients with advanced non-small cell lung cancer (NSCLC) and their relationship with prognosis.Methods:A total of 103 patients with advanced NSCLC at Shanghai University of Medicine & Health Sciences Affiliated Chongming Hospital from January 2020 to October 2021 were selected as the NSCLC group, and 100 healthy volunteers who underwent physical examinations at our hospital during the same period were selected as the control group. Fluorescent quantitative PCR was used to determine and compare the levels of serum miR-499 and miR-362 in the two groups, and the relationship between the two indexes and different clinical characteristics of NSCLC patients was analyzed. According to the clinical outcome of 2-year follow-up, the patients were divided into survival group and death group, and the levels of serum miR-499 and miR-362 were compared between the two groups. The predictive value of miR-499 and miR-362 levels on the prognosis of advanced NSCLC patients were analyzed using receiver operator characteristic (ROC) curves.Results:The serum miR-499 level in the NSCLC group (0.34±0.10) was lower than that in the control group (1.25±0.21), while the miR-362 level (1.13±0.27) was higher than that in the control group (0.63±0.15) ( t=18.26, P<0.001; t=16.32, P<0.001). There were statistically significant differences in serum miR-499 and miR-362 levels among patients with different degrees of differentiation ( t=11.12, P<0.001; t=16.35, P<0.001), TNM staging ( t=13.64, P=0.002; t=8.73, P=0.010) and lymph node metastasis ( t=10.02, P=0.003; t=9.65, P=0.004). The serum miR-499 level in the death group ( n=77) (0.24±0.06) was lower than that in the survival group ( n=26) (0.35±0.09), while the miR-362 level (1.54±0.32) was higher than that in the survival group (1.08±0.21), with statistically significant differences ( t=8.06, P=0.006; t=8.67, P=0.005). ROC curve analysis showed that the sensitivity of miR-499 and miR-362 in predicting the prognosis of advanced NSCLC patients was 73.46% and 75.85%, respectively, with specificity of 64.42% and 65.61%, AUC of 0.739 (95% CI: 0.662-0.805) and 0.743 (95% CI: 0.640-0.793) ; the sensitivity, specificity, and AUC of serum miR-499 combined with miR-362 in predicting the prognosis of advanced NSCLC patients were 87.63%, 85.34%, and 0.875 (95% CI: 0.698-0.897), respectively; the combined prediction of miR-499 and miR-362 for AUC area was higher than the individual prediction ( Z=4.83, P=0.013; Z=5.17, P=0.009) . Conclusion:Advanced NSCLC patients show significant abnormal serum level of miR-499 and miR-362, and as the severity of the disease progressed, the serum level of miR-499 is downregulated more significantly and miR-362 is upregulated more significantly. The combined detection of miR-499 and miR-362 levels has certain predictive value for the prognosis of advanced NSCLC patients.