ObjectiveThis paper aims to systematically reveal the effect difference and mechanisms of Zishenwan against chronic prostatitis （CP） before and after salt-processing of Anemarrhenae rhizoma and Phellodendri chinensis cortex based on an integrated strategy of ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry （UPLC-Q-Orbitrap-MS/MS）， network pharmacology， and serum metabolomics. MethodsZishenwan samples before and after salt-processing of Anemarrhenae rhizoma and Phellodendri chinensis cortex were extracted by alcohol-water dual extraction. The chemical components of each sample were detected by UPLC-Q-Orbitrap-MS/MS， and differential components were screened by multivariate statistical analysis. Network pharmacology analysis was performed based on the identified chemical components of Zishenwan to construct a protein-protein interaction （PPI） network of "component， target， and pathway"， and the core components， targets， and pathways of Zishenwan against CP were screened. Forty-two male Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a Qianliekang group （1.54 g·kg^-1）， low- and high-dose raw Zishenwan groups （1.8， 5.4 g·kg^-1）， and low- and high-dose salt-processed Zishenwan groups （1.8， 5.4 g·kg^-1）. The CP rat model was established by intraprostatic injection of carrageenan. After one week of recovery， the rats were administered the corresponding drugs for 21 days， while those in the blank group and model group received the same volume of normal saline. After the experiment， serum and tissue samples were collected to evaluate pharmacodynamic indicators including organ indices， histopathology， and inflammatory factors in serum. Subsequently， untargeted serum metabolomics technology was used to analyze metabolite changes and perform pathway enrichment analysis. The network pharmacology was used to construct a network of "differential metabolite， reaction， enzyme， and gene". ResultsA total of 76 components were identified in raw and salt-processed Zishenwan， and 34 differential components were screened by multivariate statistical analysis. Among them， the contents of 14 components， including berberine， berberrubine， and phellodendrine， increased after salt-processing， while the contents of 20 components， such as neomangiferin， decreased. The 28 active components and 185 potential targets were screened out by network pharmacology. The core components included berberine， phellodendrine， magnoflorine， and jatrorrhizine， and the core targets included signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， and transcription factor AP-1 （JUN）. These targets were significantly enriched in pro-inflammatory signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and mitogen-activated protein kinase （MAPK）. Compared with the model group， all Zishenwan administration groups showed decreased prostate index， reduced levels of interleukin （IL）-1β， IL-18， and B-cell lymphoma-2 （Bcl-2） in serum （P<0.05， P<0.01）， as well as varying degrees of alleviation in histopathological damage. At the same dose， compared with the raw Zishenwan groups， the salt-processed Zishenwan groups showed lower prostate index， pathological scores， and IL-1β， IL-18， and Bcl-2 levels in serum， but the differences were not statistically significant. Metabolomics reveals that 38 differential metabolites were reversed after salt-processed Zishenwan administration. Both raw and salt-processed Zishenwan regulated pathways such as β-alanine metabolism and tryptophan metabolism. In addition to the common regulated pathways， the salt-processed group specifically regulated pantothenate and coenzyme A biosynthesis， pyrimidine metabolism， and arginine and proline metabolism. The intersecting pathways between network pharmacology and metabolomics were tryptophan metabolism and arginine and proline metabolism， with overlapping targets including monoamine oxidase A （MAOA） and arginase 1 （ARG1）. ConclusionThe increased contents of components such as berberine and phellodendrine in salt-processed Zishenwan may enhance its therapeutic effect on CP by inhibiting the PI3K/Akt and MAPK signaling pathways， along with multi-target regulation of tryptophan， arginine， and pantothenate metabolism pathways to comprehensively regulate inflammatory and immune responses.

The corona virus disease 2019(COVID-19)infection has assumed global pandemic status in a short period of time since its outbreak.This public health crisis has inflicted unprecedented damage and challenges to more than 200 countries and regions around the word.As the peak of the epidemic gradually subsides,an increasing amount of attention has been shifted to the issue of long-term sequelae in COVID-19 patients.These sequelae are manifested as the continuous dysfunction of multiple organ systems and are known as Long COVID.In response to this new issue,clinical pathological research has continuously made new progress,posing new requirements and challenges for the pre-vention and treatment of Long COVID.This article aims to review the progress of clinical pathological research on Long COVID in recent years,with the expectation of providing new ideas and methods for the prevention and treatment of this disease.

Objective:To investigate the expression of Cullin associated NEDD8 dissociated protein 1 in colorectal cancer and its effect on the biological behavior of colorectal cancer.Method:A total of 70 pairs of colorectal cancer and paired normal tissue specimens were collected from Jun to Dec 2017 at the Department of Gastrointestinal Surgery at Peking University People's Hospital. Immunohistochemistry was used to detect the expression of Cullin associated NEDD8 dissociated protein 1 and analyze its relationship with clinical pathological indicators and prognosis. CCK8, colony formation assay, transwell assay, and wound healing assay were used to evaluate the effects of Cullin associated NEDD8 dissociated protein 1 on the proliferation, migration, and invasion ability of colon cancer cells.Result:Compared with normal tissues, Cullin associated NEDD8 dissociated protein 1 was highly expressed in colorectal cancer (Immunohistochemistry score: 3.685±1.257 vs. 2.000±0.851, Z=6.536, P<0.001). The expression level of Cullin associated NEDD8 dissociated protein 1 was significantly correlated with T stage ( χ2=5.67, P=0.017), N stage ( χ2=7.20, P=0.007), and pathology stage ( χ2=4.66, P=0.031). Patients with high expression of Cullin associated NEDD8 dissociated protein 1 had a worse prognosis than those with low expression ( χ2=4.80, P=0.037). Knocking down Cullin associated NEDD8 dissociated protein 1 significantly reduced the proliferation, colony formation, and invasive migration ability of DLD1 cells (all P<0.05). Conclusion:Cullin associated NEDD8 dissociated protein 1 is significantly overexpressed in colorectal cancer and has a promoting effect on the occurrence and development of colorectal cancer.

Androgenic alopecia (AGA) stands as a prevalent and challenging dermatological condition in clinical practice. Its pathogenesis is complex and the condition is prone to recurrence, which seriously affects the physical and mental health of patients. This review synthesized recent advancements in understanding the multifaceted mechanisms underlying AGA progression. It delineated the intricate interplay among genetic predispositions, hormonal influences, cytokine-mediated regulations, molecular pathway activations, and alterations in the hair follicle microenvironment. By elucidating these diverse factors and their interactions, this article aimed to provide a theoretical basis and reference for new targets of action for the clinical treatment of AGA.

The corona virus disease 2019(COVID-19)infection has assumed global pandemic status in a short period of time since its outbreak.This public health crisis has inflicted unprecedented damage and challenges to more than 200 countries and regions around the word.As the peak of the epidemic gradually subsides,an increasing amount of attention has been shifted to the issue of long-term sequelae in COVID-19 patients.These sequelae are manifested as the continuous dysfunction of multiple organ systems and are known as Long COVID.In response to this new issue,clinical pathological research has continuously made new progress,posing new requirements and challenges for the pre-vention and treatment of Long COVID.This article aims to review the progress of clinical pathological research on Long COVID in recent years,with the expectation of providing new ideas and methods for the prevention and treatment of this disease.

Objective:To investigate the expression of Cullin associated NEDD8 dissociated protein 1 in colorectal cancer and its effect on the biological behavior of colorectal cancer.Method:A total of 70 pairs of colorectal cancer and paired normal tissue specimens were collected from Jun to Dec 2017 at the Department of Gastrointestinal Surgery at Peking University People's Hospital. Immunohistochemistry was used to detect the expression of Cullin associated NEDD8 dissociated protein 1 and analyze its relationship with clinical pathological indicators and prognosis. CCK8, colony formation assay, transwell assay, and wound healing assay were used to evaluate the effects of Cullin associated NEDD8 dissociated protein 1 on the proliferation, migration, and invasion ability of colon cancer cells.Result:Compared with normal tissues, Cullin associated NEDD8 dissociated protein 1 was highly expressed in colorectal cancer (Immunohistochemistry score: 3.685±1.257 vs. 2.000±0.851, Z=6.536, P<0.001). The expression level of Cullin associated NEDD8 dissociated protein 1 was significantly correlated with T stage ( χ2=5.67, P=0.017), N stage ( χ2=7.20, P=0.007), and pathology stage ( χ2=4.66, P=0.031). Patients with high expression of Cullin associated NEDD8 dissociated protein 1 had a worse prognosis than those with low expression ( χ2=4.80, P=0.037). Knocking down Cullin associated NEDD8 dissociated protein 1 significantly reduced the proliferation, colony formation, and invasive migration ability of DLD1 cells (all P<0.05). Conclusion:Cullin associated NEDD8 dissociated protein 1 is significantly overexpressed in colorectal cancer and has a promoting effect on the occurrence and development of colorectal cancer.

Androgenic alopecia (AGA) stands as a prevalent and challenging dermatological condition in clinical practice. Its pathogenesis is complex and the condition is prone to recurrence, which seriously affects the physical and mental health of patients. This review synthesized recent advancements in understanding the multifaceted mechanisms underlying AGA progression. It delineated the intricate interplay among genetic predispositions, hormonal influences, cytokine-mediated regulations, molecular pathway activations, and alterations in the hair follicle microenvironment. By elucidating these diverse factors and their interactions, this article aimed to provide a theoretical basis and reference for new targets of action for the clinical treatment of AGA.

ω-transaminase (ω-TA) is a natural biocatalyst that has good application potential in the synthesis of chiral amines. However, the poor stability and low activity of ω-TA in the process of catalyzing unnatural substrates greatly hampers its application. To overcome these shortcomings, the thermostability of (R)-ω-TA (AtTA) from Aspergillus terreus was engineered by combining molecular dynamics simulation assisted computer-aided design with random and combinatorial mutation. An optimal mutant AtTA-E104D/A246V/R266Q (M3) with synchronously enhanced thermostability and activity was obtained. Compared with the wild- type (WT) enzyme, the half-life t_1/2 (35 ℃) of M3 was prolonged by 4.8-time (from 17.8 min to 102.7 min), and the half deactivation temperature (T¹⁰₅₀) was increased from 38.1 ℃ to 40.3 ℃. The catalytic efficiencies toward pyruvate and 1-(R)-phenylethylamine of M3 were 1.59- and 1.56-fold that of WT. Molecular dynamics simulation and molecular docking showed that the reinforced stability of α-helix caused by the increase of hydrogen bond and hydrophobic interaction in molecules was the main reason for the improvement of enzyme thermostability. The enhanced hydrogen bond of substrate with surrounding amino acid residues and the enlarged substrate binding pocket contributed to the increased catalytic efficiency of M3. Substrate spectrum analysis revealed that the catalytic performance of M3 on 11 aromatic ketones were higher than that of WT, which further showed the application potential of M3 in the synthesis of chiral amines.
Transaminases/chemistry* ; Molecular Docking Simulation ; Amines/chemistry* ; Pyruvic Acid/metabolism* ; Enzyme Stability

In unicompartmental replacement surgery, there are a wide variety of commercially available unicompartmental prostheses, and the consistency of the contact surface between the common liner and the femoral prosthesis could impact the stress distribution in the knee after replacement in different ways. Medial tibial plateau fracture and liner dislocation are two common forms of failure after unicompartmental replacement. One of the reasons is the mismatch in the mounting position of the unicompartmental prosthesis in the knee joint, which may lead to failure. Therefore, this paper focuses on the influence of the shape of the contact surface between the liner and the femoral prosthesis and the mounting position of the unicompartmental prosthesis on the stress distribution in the knee joint after replacement. Firstly, a finite element model of the normal human knee joint was established, and the validity of the model was verified by both stress and displacement. Secondly, two different shapes of padded knee prosthesis models (type A and type B) were developed to simulate and analyze the stress distribution in the knee joint under single-leg stance with five internal or external rotation mounting positions of the two pads. The results showed that under a 1 kN axial load, the peak contact pressure of the liner, the peak ACL equivalent force, and the peak contact pressure of the lateral meniscus were smaller for type A than for type B. The liner displacement, peak contact pressure of the liner, peak tibial equivalent force, and peak ACL equivalent force were the smallest for type A at 3° of internal rotation in all five internal or external rotation mounting positions. For unicompartmental replacement, it is recommended that the choice of type A or type B liner for prosthetic internal rotation up to 6° should be combined with other factors of the patient for comprehensive analysis. In conclusion, the results of this paper may reduce the risk of liner dislocation and medial tibial plateau fracture after unicompartmental replacement, providing a biomechanical reference for unicompartmental prosthesis design.
Arthroplasty, Replacement, Knee/methods* ; Biomechanical Phenomena ; Finite Element Analysis ; Humans ; Knee Joint/surgery* ; Knee Prosthesis ; Tibia/surgery*

Objective:To investigate the clinicopathological characteristics and prognostic factors of Siewert Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospetcive cohort study was conducted. The clinicopathological data of 399 patients with AEG who were admitted to Peking University People′s Hospital from January 1998 to December 2015 were collected. There were 318 males and 81 females, aged 66(range, 19-87)years. Observation indicators: (1) clinicopathological characteristics of Siewert Ⅱ and Ⅲ AEG; (2) follow-up and survival; (3) prognostic factors analysis. Patients were followed up by telephone interview and outpatient examination to detect postoperative survival up to December 2018. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-rank test was used for survival analysis. Univariate and multivariate analyses were done using the COX proportional hazard model. Results:(1) Clinicopathological characteristics of Siewert Ⅱ and Ⅲ AEG. Of 399 patients, 198 cases were Siewert Ⅱ AEG and 201 cases were Siewert Ⅲ AEG. There were 130 cases undergoing transthoracic radical AEG surgery, 172 cases undergoing trans-abdominal proximal gastrectomy and 97 cases undergoing transabdominal total gastrectomy. The age, tumor diameter, cases with surgical method as transthoracic radical AEG surgery, transabdo-minal proximal gastrectomy and transabdominal total gastrectomy, the number of positive lymph nodes, cases in tumor TNM stage Ⅰ, Ⅱ, Ⅲ, Ⅳ were (65±10)years, (5.1±2.4)cm, 102, 68, 28, 17(range, 12?22), 20, 57, 117, 4 for patients with Siewert Ⅱ AEG, versus (62±12)years, (6.3±3.2)cm, 28, 104, 69,18(range, 14?27), 16, 41, 134, 10 for patients with Siewert Ⅲ AEG, showing significant differ-ences betweeen them ( t=2.83, ?3.82, χ2=66.97, U=17 407.05, 17 532.00, P<0.05). (2) Follow-up and survival. All 399 patients were followed up for 34(range, 2?160)months. The 5-year overall survival rate was 29.3% for patients with Siewert Ⅱ AEG, versus 37.0% for patients with Siewert Ⅲ AEG, showing no significant difference betweeen them ( χ2=1.46, P>0.05). The median survival time and 5-year overall survival rate were 29.0 months [95% confidence interval ( CI) as 23.4?34.6 months] and 22.9% for patients undergoing transthoracic radical AEG surgery, 43.0 months(95% CI as 33.9?52.1 months) and 34.7% for patients undergoing transabdominal proximal gastrectomy, 54.0 months (95% CI as 37.6?70.4 months)and 44.3% for patients undergoing transabdominal total gastrectomy, showing a significant difference in the survival among the 3 groups ( χ2=13.81, P<0.05). Of the 198 Siewert Ⅱ AEG patients, the 5-year overall survival rate was 24.6% for the 96 patients undergoing transabdominal surgery, versus 35.4% for the 102 patients undergoing transthoracic surgery, showing no significant difference in the survival between them ( χ2=3.10, P>0.05). Of the 201 Siewert Ⅲ AEG patients, the 5-year overall survival rate was 40.0% for the 173 patients undergoing transabdominal surgery, versus 16.1% for the 28 patients undergoing transthoracic surgery, showing a significant difference between them ( χ2=11.32, P<0.05). (3) Prognostic factors analysis. Results of univariate analysis showed that surgical method, pathological N staging, patholgical M staging were related factors for prognosis of Siewert Ⅱ and Ⅲ AEG ( hazard ratio=0.68, 1.25, 2.18, 95% CI as 0.54?0.86, 1.15?1.36, 1.28?3.73, P<0.05). Results of multivariate analysis showed that transthoracic approach, pathological stage N2?N3 and pathological stage M1 were independent risk factors for prognosis of Siewert Ⅱ and Ⅲ AEG ( hazard ratio=0.64, 1.25, 2.18, 95% CI as 0.51?0.80, 1.16?1.35, 1.28?3.70, P<0.05). Conclusions:Compared with Siewert Ⅲ AEG, Siewert Ⅱ AEG has a smaller tumor diameter, less positive lymph nodes, poorer prognosis. Transthoracic approach is preffered for the Siewert Ⅱ AEG. Transthoracic approach, pathological stage N2?N3 and pathological stage M1 are independent risk factors for prognosis of Siewert Ⅱ and Ⅲ AEG.