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

Objective:To evaluate the value of modified gastroscopic laryngeal mask airway (LMA) for airway management under general anesthesia in the patients with liver cirrhosis undergoing endoscopic esophageal variceal ligation (EVL).Methods:Sixty-two American Society of Anesthesiologists physical status Ⅱor Ⅲ patients with liver cirrhosis of either sex, aged 25-64 yr, with body mass index of 18-30 kg/m 2, undergoing endoscopic EVL with general anesthesia, were divided into 2 groups ( n=31 each) using a random number table method: tracheal tube group (group T) and modified gastroscopic LMA group (group L). After induction of anesthesia, a tracheal tube was inserted in group T, and a modified gastroscopic LMA was inserted and the patients were mechanically ventilated to maintain P ETCO 2 at 30-40 mmHg in group L. Successful tracheal intubation or insertion of modified gastroscopic LMA, successful ligator insertion and duration of ligator insertion were recorded.The occurrence of intraoperative hypotension, bradycardia and hypoxemia and consumption of propofol and remifentanil were recorded.At 1 min after tracheal intubation or right placement of LMA (T 1), immediately after the ligator insertion (T 2) and at the end of operation (T 3), Peak (P peak) and mean (P mean) airway pressure were monitored, and airway leak pressure in group L was measured.The extubation time, duration of post-anesthesia care unit stay and bucking during extubation were recorded.The occurrence of sore throat and nausea and vomiting was recorded within 6 h after operation.Postoperative satisfaction scores of endoscopists and patients were also recorded. Results:Sixty-one patients were finally enrolled in the study, with 31 in group T and 30 in group L. Compared with group T, no significant changes were found in the success rate of tracheal intubation or LMA placement, success rate of ligator insertion, P mean at each time point, incidence of postoperative nausea and vomiting, and postoperative satisfaction score of endoscopists ( P>0.05), duration of the ligator insertion was significantly shortened, P peak at each time point was decreased, the incidence of intraoperative hypotension and bradycardia was decreased, the consumption of propofol and remifentanil was reduced, the incidence of bucking during extubation and postoperative sore throat was reduced, and extubation time and duration of post-anesthesia care unit stay was shortened, and satisfaction scores of patients were increased in group L ( P<0.05). No hypoxemia was found in two groups.Airway leak pressure was maintained at 24-26 cmH 2O at each time point in group L. Conclusions:Modified gastroscopic LMA can be safely and effectively used for airway management under general anesthesia in the patients with liver cirrhosis undergoing EVL.

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 clinical outcomes of patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection.Methods:Patients who undergoing radical surgical resection for ICC from Jan 2015 to Apr 2021 at the Department of General Surgery, the First Affiliated Hospital of Anhui Medical University were included in this retrospective cohort study.Results:There were 67 patients in the final analysis, The median follow-up duration was 14 months (range: 1-60 months). Firty three patients (79.1%) had tumor recurrence, 52 patients (77.6%) died, Among them, 49 patients (73.1%) died from tumor recurrence. The 1-、2-、and 3-year accumulated disease-free and overall survival rate were 35.6%, 19.6%, 16.8% and 53.7%, 32.4%, 20.8%. respectively. The overall survival rate of the group without microvascular invasion was significantly better than those of the group with microvascular invasion ( χ2=5.916, P=0.015). CA19-9≥1 000 U/ml was the only independent risk factor for the disease-free survival. CA19-9≥1 000 U/ml、blood loss≥600 ml、microvascular invasion and tumor recurrence were the independent risk factors for the overall survival. Conclusion:For ICC patients with single tumor, when the tumor diameter is less than 5 cm and has no microvascular invasion, surgical resection is recommended, and a satisfactory prognosis could be achieved.