Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Objective:To evaluate the clinical effect of derotational distal femoral osteotomy (DDFO) combined with medial patellofemoral ligament (MPFL) reconstruction assisted by digital orthopedic technique in the treatment of recurrent patellar dislocation with enlarged femoral anteversion angle (FAA).Methods:TThe clinical data of 18 patients (4 men and 14 women; mean age 22.1±0.7 years; range, 18-26 years) with recurrent patellar dislocation (FAA≥30°) admitted to Digital Orthopedic Technology Clinical Application Center in Tianjin hospital from May 2022 to December 2023 were retrospectively analyzed. The average number of patella dislocations were 3.6±0.4 (range, 2-8 times), with a mean symptom duration of 4.3±0.4 years (range, 2-7 years). According to Dejour classification of femoral trochlea dysplasia, there were 5 cases of type A, 3 cases of type B, 6 cases of type C and 4 cases of type D. All patients underwent 3D CT scanning and digital modeling before operation. Based on the modeling results, personalized osteotomy and orthopedic integration guide were designed and printed to direct intraoperative DDFO and MPFL reconstruction. Radiological parameters, knee function and complications were assessed during follow-up. Knee function assessments included visual analogue scale (VAS), Intemational Knee Documentation Committee Knee Form (IKDC), Kujala, Lysholm and Tegner score. The radiological parameters included FAA, patellar tilt angle (PTA), tibial tuberosity-trochlear groove distance (TT-TG) and caton-deschamps index (CDI).Results:All patients underwent surgery and were followed up for 15.4±2.8 months (range, 12-20 months). Complications occurred in 3 patients, including deep venous thrombosis in 2 cases and wound effusion in 1 case. No other complications such as wound infection, nerve injury, vascular injury, fracture nonunion or patella dislocation were recorded. The VAS score improved from 5.4±0.3 preoperatively to 2.1±0.2 at one year postoperatively. The IKDC score improved from 44.4±2.7 to 79.2±1.9 points. The Kujala score improved from 51.8±2.6 to 86.1±1.6, the Lysholm from 49.8±2.5 to 84.9±1.5, and the Tegner score from 2.2±0.2 to 4.1±0.2. The FAA decreased from 39.7°±1.2° to 14.9°±0.2°, the PTA from 33.1°±2.6° to 12.6°±1.4°, and the TT-TG from 20.2±0.6 to 13.9±0.4 mm. The differences between time of all the above-mentioned parameters were statistically significant ( P<0.05). The CDI remained stable, which changed from 1.03±0.02 preoperatively to 1.07±0.01 one year after operation ( P>0.05). Conclusions:After the application of DDFO combined with MPFL reconstruction assist by personalized osteotomy and orthopedic integrated guide, the patient's knee function and imaging parameters were significantly improved at one-year follow-up. In the treatment of recurrent patellar dislocation with enlarged FAA, good early clinical efficacy could be achieved with this operation.

Objective:To evaluate the clinical effectiveness of high tibial osteotomy (HTO) assisted by digital orthopedic techniques in the treatment of varus knee osteoarthritis secondary to tibial fracture malunion.Methods:The clinical data were retrospectively analyzed of the 16 patients who had been admitted to Clinical Application Center of Digital Orthopedic Technology, Tianjin Hospital for varus knee osteoarthritis secondary to tibial fracture malunion from April 2022 to October 2023. There were 6 men and 10 women, with an age of (56.3±1.6) years and a mean body mass index of (23.8±0.9) kg/m 2. HTO was performed for all the patients using patient-specific instrumentation integrated osteotomy and orthopedic guide which was designed and printed with digital orthopedic techniques. If preoperative imaging indicated symptomatic meniscus injury (tear), intraarticular free body, or intercondylar fossa stenosis in a patient, arthroscopic clearance was first conducted before subsequent performance of HTO at one stage. Clinical effectiveness was evaluated by measuring and comparing hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), posterior tibial slope (PTS), lower limb weight-bearing line (WBL) ratio, Western Ontario and McMaster University (WOMAC) osteoarthritis index, visual analogue scale (VAS) pain score and knee range of motion (ROM) before surgery and 12 months after surgery. Results:The operative time was (41.3±2.1) min and intraoperative fluoroscopy was performed only once in all the patients. All the wounds healed by the first stage with no such complications as hinge point fracture, wound infection, vascular injury, nerve injury, delayed union or nonunion of fracture, lower limb deep venous thrombosis, loosening of internal fixation, or plate rupture. The follow-up time for the 16 patients was (16.3±0.7) months. At 12 months after surgery, the HKA (179.5°±0.5°), MPTA (91.7°±0.5°), WBL ratio (61.2%±0.4%), WOMAC osteoarthritis index [(12.8±0.8) points], VAS pain score [(1.8±0.3) points] and knee ROM (121.8°±1.8°) were significantly better than those before surgery [166.6°±1.3°, 81.8°±0.4°, 29.6%±1.0%, (38.4±2.1) points, (4.8±0.3) points, and 110.5°±2.1°] ( P < 0.05). There was no significant difference in PTS between pre-surgery and 12 months after surgery ( P > 0.05). Conclusions:When HTO is used to treat varus knee osteoarthritis secondary to tibial fracture malunion, assistance of digital orthopedic techniques can improve HKA, MPTA, lower limb alignment, and knee ROM to reduce and recover knee function for the patients.

Objective:To evaluate the clinical effect of derotational distal femoral osteotomy (DDFO) combined with medial patellofemoral ligament (MPFL) reconstruction assisted by digital orthopedic technique in the treatment of recurrent patellar dislocation with enlarged femoral anteversion angle (FAA).Methods:TThe clinical data of 18 patients (4 men and 14 women; mean age 22.1±0.7 years; range, 18-26 years) with recurrent patellar dislocation (FAA≥30°) admitted to Digital Orthopedic Technology Clinical Application Center in Tianjin hospital from May 2022 to December 2023 were retrospectively analyzed. The average number of patella dislocations were 3.6±0.4 (range, 2-8 times), with a mean symptom duration of 4.3±0.4 years (range, 2-7 years). According to Dejour classification of femoral trochlea dysplasia, there were 5 cases of type A, 3 cases of type B, 6 cases of type C and 4 cases of type D. All patients underwent 3D CT scanning and digital modeling before operation. Based on the modeling results, personalized osteotomy and orthopedic integration guide were designed and printed to direct intraoperative DDFO and MPFL reconstruction. Radiological parameters, knee function and complications were assessed during follow-up. Knee function assessments included visual analogue scale (VAS), Intemational Knee Documentation Committee Knee Form (IKDC), Kujala, Lysholm and Tegner score. The radiological parameters included FAA, patellar tilt angle (PTA), tibial tuberosity-trochlear groove distance (TT-TG) and caton-deschamps index (CDI).Results:All patients underwent surgery and were followed up for 15.4±2.8 months (range, 12-20 months). Complications occurred in 3 patients, including deep venous thrombosis in 2 cases and wound effusion in 1 case. No other complications such as wound infection, nerve injury, vascular injury, fracture nonunion or patella dislocation were recorded. The VAS score improved from 5.4±0.3 preoperatively to 2.1±0.2 at one year postoperatively. The IKDC score improved from 44.4±2.7 to 79.2±1.9 points. The Kujala score improved from 51.8±2.6 to 86.1±1.6, the Lysholm from 49.8±2.5 to 84.9±1.5, and the Tegner score from 2.2±0.2 to 4.1±0.2. The FAA decreased from 39.7°±1.2° to 14.9°±0.2°, the PTA from 33.1°±2.6° to 12.6°±1.4°, and the TT-TG from 20.2±0.6 to 13.9±0.4 mm. The differences between time of all the above-mentioned parameters were statistically significant ( P<0.05). The CDI remained stable, which changed from 1.03±0.02 preoperatively to 1.07±0.01 one year after operation ( P>0.05). Conclusions:After the application of DDFO combined with MPFL reconstruction assist by personalized osteotomy and orthopedic integrated guide, the patient's knee function and imaging parameters were significantly improved at one-year follow-up. In the treatment of recurrent patellar dislocation with enlarged FAA, good early clinical efficacy could be achieved with this operation.

OBJECTIVE To offer a reference for the treatment of Mycobacterium iranicum infection by analyzing the diagnosis and management of a single case alongside literature-reported cases.METHODS Through case report and literature reviews,this study synthesized the clinical features,therapeutic regimens,and patient outcomes of those infected with M.iranicum.RESULTS In the single case documented in this report,subsequent to clinical pharmacists'involvement in the consultation,the patient was prescribed a therapeutic regimen comprising levofloxacin(0.5 g,qd,ivgtt)+Clarithromycin sustained-release tablets(1 000 mg,qd,po)+Ethambutol tablets(0.75 g,qd,po).The patient exhibited clinical improvement and was discharged after treatment.This article integrated 12 published studies,encompassing 13 patients(7 male and 6 female),of whom 69.23%were aged≥50 years.Patients infected with M.iranicum exhibited non-specific clinical manifestations and imaging features,with pulmonary infection as the primary presentation.Antimicrobial susceptibility test revealed that M.iranicum was susceptible to multiple agents,including amikacin,clarithromycin,linezolid,and ethambutol.The three-drug combination therapy was the most frequently employed regimen.In terms of clinical outcomes,there were 9 cases(69.23%)of clinical cure,3 cases(23.08%)of bacteriological negativity conversion,and 1 case(7.69%)of treatment failure.CONCLUSIONS For M.iranicum infection,a triple-drug therapeutic regimen consisting of three agents with distinct mechanisms of action selected from amikacin,clarithromycin,moxifloxacin,levofloxacin,minocycline,ethambutol,and other relevant drugs may represent a relatively optimal strategy.

Objective:To evaluate the clinical effectiveness of high tibial osteotomy (HTO) assisted by digital orthopedic techniques in the treatment of varus knee osteoarthritis secondary to tibial fracture malunion.Methods:The clinical data were retrospectively analyzed of the 16 patients who had been admitted to Clinical Application Center of Digital Orthopedic Technology, Tianjin Hospital for varus knee osteoarthritis secondary to tibial fracture malunion from April 2022 to October 2023. There were 6 men and 10 women, with an age of (56.3±1.6) years and a mean body mass index of (23.8±0.9) kg/m 2. HTO was performed for all the patients using patient-specific instrumentation integrated osteotomy and orthopedic guide which was designed and printed with digital orthopedic techniques. If preoperative imaging indicated symptomatic meniscus injury (tear), intraarticular free body, or intercondylar fossa stenosis in a patient, arthroscopic clearance was first conducted before subsequent performance of HTO at one stage. Clinical effectiveness was evaluated by measuring and comparing hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), posterior tibial slope (PTS), lower limb weight-bearing line (WBL) ratio, Western Ontario and McMaster University (WOMAC) osteoarthritis index, visual analogue scale (VAS) pain score and knee range of motion (ROM) before surgery and 12 months after surgery. Results:The operative time was (41.3±2.1) min and intraoperative fluoroscopy was performed only once in all the patients. All the wounds healed by the first stage with no such complications as hinge point fracture, wound infection, vascular injury, nerve injury, delayed union or nonunion of fracture, lower limb deep venous thrombosis, loosening of internal fixation, or plate rupture. The follow-up time for the 16 patients was (16.3±0.7) months. At 12 months after surgery, the HKA (179.5°±0.5°), MPTA (91.7°±0.5°), WBL ratio (61.2%±0.4%), WOMAC osteoarthritis index [(12.8±0.8) points], VAS pain score [(1.8±0.3) points] and knee ROM (121.8°±1.8°) were significantly better than those before surgery [166.6°±1.3°, 81.8°±0.4°, 29.6%±1.0%, (38.4±2.1) points, (4.8±0.3) points, and 110.5°±2.1°] ( P < 0.05). There was no significant difference in PTS between pre-surgery and 12 months after surgery ( P > 0.05). Conclusions:When HTO is used to treat varus knee osteoarthritis secondary to tibial fracture malunion, assistance of digital orthopedic techniques can improve HKA, MPTA, lower limb alignment, and knee ROM to reduce and recover knee function for the patients.

Objective:To compare the maternal and fetal outcomes of women with cervical insufficiency (CI) undergoing McDonald cerclage (MC) and laparoscopic cervicoisthmic cerclage (LCC), so as to provide evidence for the selection of cerclage methods.Methods:A retrospective trial was carried out in the First Affiliated Hospital of Sun Yat-sen University from January 2010 to December 2020. A total of 221 women who underwent the prophylactic cerclage were divided into MC group ( n=54), LCC with MC history group ( n=28) and LCC without MC history group ( n=129) by the mode of operation and whether the pregnant women who underwent LCC had MC history. General clinical data, pregnancy complications and pregnancy outcomes were compared between the three groups. Results:(1) General clinical data: the proportion of women accepted cervical cerclage during pregnancy in MC group, LCC with MC history group and LCC without MC history group were 100.0% (54/54), 7.1% (2/28) and 27.1% (35/129), respectively ( P<0.001). The indications of the three groups showed statistical significance ( P=0.003), and the main indication was the history of abortion in the second and third trimester [75.9% (41/54) vs 89.3% (25/28) vs 84.5% (109/129)]. (2) Pregnancy complications: the incidence of abnormal fetal position [7.8% (4/51) vs 17.4% (4/23) vs 19.8% (24/121)], placenta accrete [5.9% (3/51) vs 13.0% (3/23) vs 11.6% (14/121)], uterine rupture [0 vs 4.3% (1/23) vs 5.8% (7/121)] in the MC group were all lower than those in LCC with MC history and LCC without MC history groups. However, there were no statistical significances (all P>0.05). Intrauterine inflammation or chorioamnionitis [15.7% (8/51) vs 0 vs 0.8% (1/121)] and premature rupture of membrane [23.5% (12/51) vs 4.3% (1/23) vs 0] were both significantly higher in MC group than those in LCC with MC history and LCC without MC history groups (all P<0.001). (3) Pregnancy outcomes: the cesarean section rate was significantly lower in MC group (41.2%, 21/51) than that in LCC with MC history group (100.0%, 23/23) and LCC without MC history group (100.0%, 121/121; P<0.001). MC group was associated with lower expenditure than LCC with MC history and LCC without MC history groups (12 169 vs 26 438 vs 27 783 yuan, P<0.001). The success rates of live birth cerclage did not differ significantly in MC (94.4%, 51/54), LCC with MC history (82.1%, 23/28) and LCC without MC history (93.8%, 121/129) groups ( χ2=5.649, P=0.059). There was no significant difference in neonatal intensive care unit occupancy, neonatal birth weight and neonatal asphyxia between the three groups (all P>0.05). Conclusions:Both LCC and MC are the treatment choice for women with CI, which may get similar liver birth. However, MC has the advantages of low cesarean section rate, economical and easy operation. Therefore, MC is recommended as the first choice for CI patients, and LCC is for women with failed MC.

[Objective]To investigate the disturbance between Th17 and Treg cell balance in ovarian endometriosis patients.[Methods]Case-control study comparing 40 women with histo-pathologically confirmed ovarian endometriosis and with 40 control infertility women without visible endometriosis foci ,pelvic inflammations who were subjected to laparoscopic surgery during the same period. Peripheral blood,peritoneal fluid,ovarian ectopic endometrial tissue and eutopic endometrial tissue of ovarian endometriosis patients and controls were collected during surgery. T lymphocytes subpopulations in peripheral blood were analyzed by flow cytometry using specific monoclonal antibodies recognizing CD4+,CD25+and CD127-markers and CD3+,CD8-and IL-17A+markers. Then, IL-17,IL-22,IL-10and TGF-βconcentration in the serum and peritoneal fluid was determined using enzyme linked immunosorbent assay(ELISA). Also,Q-PCR was performed to verify Foxp3 mRNA and ROR-γt mRNA expression differences in eutopic and ectopic endometrial tissue.[Results]1.The percentage of CD4+CD25+CD127-Treg cells was significantly decreased in the peripheral blood ofwomen with ovarian endometriosis compared with control women. On the other hand ,the proportion of CD3+CD8-IL-17A+Th17 cells was significantly increased in the peripheral blood of women with endometriosis compared with control wom en. 2. Comparing with the controls ,the concentration of IL-17 and IL-22 was significantly higher in the serum of women with ovarian endometriosis ,and the levels of IL-10 and TGF-β were significantly lower in the serum of women with endometriosis. On the contrast ,in the peritoneal fluid of women with ovarian endometriosis ,the concentration of IL-17 and IL-22 were lower ,and the concentration of IL-10 and TGF-β were significantly higher than the controls. 3.Foxp3 mRNA expression level was significantly elevated in ectopic endometrial tissue of patients with ovarian endometriosis compared with eutopic endometrial tissue ,while the ROR-γt mRNA expression level of ectopic endometrial tissue was significantly decreased than eutopic endometrial tissue.[Conclusion]The present study verifies the imbalance of Th17/Treg in peripheral blood ,peritoneal fluid and endometrial tissue in ovarian endometriosis patients ,which implies the immune dysregulation and the disturbance of immunity homeostasis in the establishment and progression of endometriosis.