Background and objective Pembrolizumab(PEM)has been shown to be effective in clinical trials for the treatment of advanced non-small cell lung cancer(NSCLC),but clinical trials were based on cohorts of patients selected on specific criteria,and whether the findings are consistent with real-world patients is debatable.The aim of this study is to evaluate the efficacy and safety of PEM in the treatment of advanced NSCLC based on real-world data.Methods A retro-spective collection of real-world data from patients with advanced NSCLC receiving PEM was conducted.Propensity score matching was used to eliminate inter-group differences and assess the efficacy and safety of PEM compared to chemotherapy.Results Among 450 matched patients,the incidence rates of any-grade adverse events were 79.87％in the PEM group and86.71％inthe chemotherapy group,while the incidence rates of grade＞3 adverse events were 4.03％and 7.31％,respectively.The objective response rates were 48.63％for PEM and 36.00％for chemotherapy(P=0.011).The median progression-free survival was 15.5 months for PEM and 8.8 months for chemotherapy(P＜0.001),and the median overall survival was not reached for PEM and 26.2 months for chemotherapy(P＜0.001).Conclusion PEM treatment for advanced NSCLC demonstrates favorable survival outcomes and acceptable safety in real-world clinical practice.

Objective:To investigate the prognostic relationship between serum KL-6 level and rheumatoid arthritis(RA)combined with interstitial lung disease(RA-ILD).Methods:In Affiliated Hospital of Inner Mongolia Medical University from January 2018 to January 2021,seventy patients with RA were selected and divided into RA-ILD group(34 cases)and RA(36 cases)accord-ing to whether they were complicated with ILD,clinicopathological characteristics of the two groups of patients were analyzed by uni-variate analysis,focusing on the comparison of the expression level of KL-6 in the serum of the two groups and the correlation analysis with laboratory indexes,lung function and imaging,multivariate Logistic regression analysis risk factors affecting RA-ILD.Results:There were significant differences in gender,smoking history,age,age of onset,course of disease,DAS28,KL-6,WBC,UA,RF,anti-CCP antibody,TLC%Pred and DLCO%Pred between the two groups(P<0.05).In RA-ILD group,the proportion of clinical symp-toms was more prominent,joint pain was more prominent,and the thickening of pleural adhesion was more prominent on HRCT;Spearson correlation analysis showed that the level of serum KL-6 in RA-ILD group was significantly negatively correlated with TLC%Pred,VC%Pred and DLCO%Pred(P<0.05);there was a significant positive correlation with RF and anti-CCP antibody levels(P<0.05);there was no significant correlation with FEV1%Pred and FEV1/FVC(P>0.05);expression level of KL-6 in RA-ILD group was significantly higher than that in RA group before treatment,and there was no significant difference after treatment(P>0.05);Fol-lowed up for one year,six patients died in RA-ILD group.The expression level of KL-6 in death group was significantly higher than that in non death group(P<0.05);multivariate Logistic regression analysis showed that old age,male,smoking,increased anti CCP antibody and KL-6 were independent risk factors for RA-ILD(P<0.05);the maximum area under the ROC curve predicted by serum KL-6 was 0.802,the 95%CI was 0.743～0.866,the sensitivity was 0.853,the specificity was 0.827,and the maximum area under the ROC curve detected jointly was 0.854,indicating that the prediction ability of the model was strong.Conclusion:Serum KL-6 levels in RA-ILD patients are significantly increased.KL-6 can be used as a serological index for early detection of ILD,and combined with lung function detection can detect ILD earlier.Early diagnosis is of great significance for treatment and prognosis.

Objective:To explore the economic applicability and safetyof the novel uterovaginal pubic comb suspension(UPCS)surgery with Mersilene tape in the treatment of pelvic organ prolapse(POP).Methods:A ret-rospective analysis was conducted on the clinical data of patients who underwent UPCS surgery due to POP from January 1st,2021 to February 28,2023.They were divided to the UPCS surgery with Mersilene tape group(group A)and suspension surgery with Y-shaped mesh group(group B)respectively.The POP-Q indication points,sus-pension surgery duration,intraoperative bleeding volume,material expense,postoperative catheter retention time,anal exhaust time and hospitalization duration were recorded for both groupbefore and after surgery.Evaluate the severity of POP related symptoms in patients before and after surgery using the pelvic Floor Distress Invento-ry-short Form 20(PFDI-20)and Pelvic Organ Prolapsed/Urinary Incontinence Sexual Questionnaire-12(PISQ-12),and follow up and observe the patients and analyze the complications.Results:A total of 17 POP patients were included in the study.There were 12 patients in group A while 5 patients in group B.The suspension material expense of group A was considerably lower than that of group B(P＜0.05).There was no significant difference between the two groups in preoperative PFDI-20 score,preoperative PISQ-12 score,UPCS surgery duration,intr-aoperative bleeding volume,postoperative urinary catheter retention time,postoperative anal exhaust time and hospitalization duration.All patients showed stable vital signs during the surgery and no severe complications were reported.Compared with the preoperative status,the positions of the Aa,Ba,and C indicatorpoint in group A and group B were all increased significantly(P＜0.05).The PFDl-20 and PISQ-12 scores of the two groups at the last follow-up after surgery showed significant improvement compared to those before surgery(P＜0.05).No signifi-cant difference was found in the PFDI-20 and PISQ-12 scores between the two groups after surgery(P＞0.05).There were no significant differences in the postoperative complications between the two groups(P＞0.05).Con-clusions:Compared with suspension surgery with Y-shaped mesh,UPCS surgery with Mersilene tape is safe and effective in the treatment of POP.The UPCS surgery with Mersilene tape showed better cost-effectiveness in the treatment of POP,and the surgical steps are relatively simple.Therefore,UPCS surgery with Mersilene tape was worthy of promotion in clinical practice.

Objective:To investigate whether transplantation of gingival mesenchymal stem cells (GMSCs) can inhibit radiation-induced senescence of alveolar epithelial cells type Ⅱ (AECⅡ) and its role in the prevention of radiation-induced pulmonary fibrosis (RIPF).Methods:Mouse type Ⅱ alveolar epithelial cells (MLE12) were irradiated with 6 Gy X-rays and then co-cultured with GMSCs. The extent of cellular senescence of MLE12 cells was assessed by cell morphology, β-Gal staining, and senescence secretion-associated phenotype (SASP) assay. RIPF model was constructed by unilaterally irradiating the right chest of C57BL/6 mice with 17 Gy X-rays. GMSCs were transplanted 1 d after irradiation. At 180 d after irradiation, the pulmonary organ ratio, HE staining, and Masson staining were used to assess intra-pulmonary structure and interstitial collagen deposition in the lung. β-Gal immunohistochemistry and immunofluorescence co-localization with AECⅡ were measured to assess the degree of cellular senescence in the lung. The SASP expression changes in lung tissue were detected by qRT-PCR. The protein expressions in P53-P21 and P16 pathways were detected by Western blot assay. P21 expression in AECⅡ was detected by immunofluorescence co-localization assay.Results:GMSCs effectively inhibited radiation-induced senescence of MLE12 cells, reduced the ratio of radiation-elevated β-Gal positive cells by 11.8% ( t=6.72, P<0.05), and decreased the expressions of SASP (IL-6, IL-8, IL-1β) ( t=28.43, 28.43, 4.82, P<0.05). GMSCs transplantation improved the survival rate of irradiated mice, prevented radiation-induced alveolar structural collapse thickening and collagen deposition, reduced the number of senescent cells in the irradiated lung tissues by 23.9% ( t=21.83, P<0.05), and inhibited the expressions of SASP ( t=8.86, 20.63, P<0.05). GMSCs also inhibited the expression of P53-P21, P16-related proteins in MLE12 cells and lung tissues of mice after irradiation. Conclusions:GMSCs inhibit senescence-related P53-P21 and P16 pathways, prevent radiation-induced AECⅡ senescence, as well as the development of RIPF.

Objective:To establish a method for quality evaluation of Myristica fragrans Houtt. Methods:The common peak was determined with Dehydroisoeugenol as the reference peak, and the HPLC fingerprint of Myristica fragrans was established; then the common peaks were analyzed by High Resolution Liquid Chromatography-mass Spectrometry (HPLC-MS). The chemical components of the common peaks were identified through the calculation and data retrieval of the primary and secondary mass spectra of the characteristic peaks. Results:The HPLC fingerprint of Myristica fragrans was established, and the similarity degree of the 10 batches of samples was above 0.9 and 11 common peaks were established. According to the results of HPLC-MS, the components of 11 common peaks were identified as follow: Methyl eugenol (peak 1), Licarin A (peak 2), Myristol (peak 3), OdoratisolA (peak 4), 2-(3,4-Dimethoxyphenyl) butynoic acid (peak 5), Malabaricon D (peak 6), 5'-Methoxydehydroisoeugenol (peak 7), Dehydroisoeugenol (peak 8), Malabaricone C (peak 9), 4-Methoxy-6-{(2S,3S)-7-methoxy-3-methyl-5-[(1E)-1-propen-1-yl]-2,3-dihydro-1- benzofuran-2-yl}-1,3-benzodioxole (peak 10) and Licarin B (peak 11). Conclusions:The quality of Myristica fragrans could be evaluate with HPLC fingerprint method. HPLC-MS was used to analyze the chemical composition of complex components, which will provide reference for the identification and analysis of chemical components of the extracts and preparations of Traditional Chinese Medicine.

Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.

Objective:To investigate the clinical characteristics and perinatal outcomes of pregnancy with placental cystic lesions.Methods:A retrospective study was carried out on 48 pregnant women diagnosed as pregnancy complicated with placental cystic lesions from January 2000 to January 2020 at the Women′s Hospital, Zhejiang University School of Medicine. The clinical features, pathological diagnosis and perinatal outcome were analyzed.Results:The age of 48 cases was (30±5) years, and the diagnostic gestational week of ultrasound was (24±8) weeks. Twenty-five cases in which showed a cystic mass at the fetal surface were diagnosed as placental cyst. The live birth rate was 100% (25/25) and the premature birth rate was 20% (5/25). Twenty-three cases showed “honeycomb like” cystic echo. Cystic lesions of 10 cases were located in the uterine cavity connected with the margin of the normal placenta, and finally diagnosed as hydatidiform mole and coexisting fetus (HMCF). Six cases of HMCF terminated pregnancy, and the live birth rate was 4/10, the premature delivery rate was 2/4. Cystic lesions of 13 cases were located in the placenta substance, and finally diagnosed as 4 cases of placental mesenchymal dysplasia (PMD) and 9 cases of focal chorionic edema; the live birth rate was 6/13 and the premature delivery rate was 4/6. The median hCG was lower in focal chorionic edema group [80 kU/L (60-110 kU/L)] than in the groups of HMCF [240 kU/L (180-430 kU/L)] and PMD [360 kU/L (210-700 kU/L)], and the differences were statistically significant (all P<0.01). Conclusions:For pregnancy complicated with placental cystic lesions, prenatal ultrasound should be performed to evaluate the shape, location and blood flow of the lesions. Maternal serological examination and invasive prenatal diagnosis are helpful for prenatal diagnosis and treatment. Due to the difference of perinatal outcomes, maternal and fetal complications, individualized pregnancy management should be carried out.

Objective:To explore the effect of Gubi Decoction on serum related inflammatory factors and PI3K/Akt/mTOR signaling pathway in osteoarthritis model rats. Methods:Seventy SPF rats were randomly divided into the blank group, sham operation group, Glucosamine sulfate group, and the low, medium and high dose Gubi Decoction groups. Except the blank group and sham operation group, knee osteoarthritis animal models were prepared by the modified Hulth method in each group. On the 28th day after successful model preparation, the high, medium and low dose Gubi Decoction groups were given Gubi Decoction 24, 12 and 6 g/kg by gavage respectively; glucosamine sulfate group was given glucosamine sulfate tablet suspension 3 g/L by gavage, once a day for 28 days. The levels of TNF-α and IL-1β in serum were detected by ELISA. The gene expressions of PI3K, Akt and mTOR in cartilage tissue were detected by Real-PCR. The protein expressions of PI3K, Akt, p-PI3K, p-Akt and mTOR were detected by Western blot. Results:Compared with the model group, the knee joint diameter[(11.17 ± 1.81) mm, (11.60 ± 1.38) mm, (10.80 ± 1.17) mm vs. (12.57 ± 0.98) mm] of the rats in the glucosamine sulfate group and the medium and high dose Gubi Decoction groups significantly decreased ( P<0.05). The content of TNF-α [(111.43 ± 21.98) ng/L, (53.42 ± 13.25) ng/L vs. (157.89 ± 23.60) ng/L], IL-1β [(67.50 ± 18.44) ng/L, (48.22 ± 9.63) ng/L vs. (96.11 ± 14.85) ng/L] in the medium and high dose Gubi Decoction groups significantly decreased ( P<0.05), and the expression of PI3K (1.87 ± 0.17, 1.24 ± 0.49 vs. 2.19 ± 0.47), Akt (1.50 ± 0.51, 1.10 ± 0.32 vs. 2.68 ± 0.63), and mTOR (1.32 ± 0.54, 1.10 ± 0.33 vs. 2.94 ± 0.55) mRNA in the medium and high dose Gubi Decoction groups significantly decreased ( P<0.05). The expression of PI3K, Akt, p-PI3K, p-Akt in the low, medium and high dose Gubi Decoction groups significantly decreased ( P<0.05), and the expression of mTOR in the medium dose Gubi Decoction group significantly decreased ( P<0.05). Conclusion:Gubi Decoction can significantly reduce the level of inflammatory factors in the serum of osteoarthritis model rats, and its anti-inflammatory and analgesic effects may be related to PI3K/Akt/mTOR signaling pathway.

Obesity has become a major public health problem that threatens human health.Abdominal obesity, especially the increase in visceral adipose tissue(VAT), can in some cases lead to insulin resistance and other metabolism-related diseases such as diabetes, cardiovascular disease, thrombosis, and pro-inflammatory metabolic abnormalities.Metabolic syndrome is a group of clinical syndromes characterized by the co-occurrence of various metabolic diseases, including insulin resistance and inflammatory response.In a large extent, the occurrence and development of the metabolic syndrome are related to fat aging and visceral obesity related.Visceral obesity is an independent risk factor for cardiovascular events, and can be changed, so by setting realistic goals, by insisting on reasonable exercise and diet control can achieve control of visceral fat, prevention and control of the metabolic syndrome.This review reviews the concept and pathophysiology of metabolic syndrome and the relationship between visceral obesity and metabolic syndrome.

Objective: To investigate the clinical value of gallbladder-preserving cholelithotomy by natural orifice transumbilical endoscopic surgery on patients with cholecystolithiasis. Methods: A retrospective study was performed on data of 15 patients with cholecystolithiasis, who underwent gallbladder-preserving cholelithotomy by natural orifice transumbilical endoscopic surgery from April 2018 to July 2018. The operative data, including situation of operation, operative time, intraoperative hemorrhage, and postoperative complications were recorded. Results: The procedure was performed successfully in all patients with a mean operative time of 108±12 min (ranged from 92-129 min). The intraoperative hemorrhage was 10-30 mL. Eight patients suffered from slight right upper abdominal pain, and 7 patients felt slight pain in umbilical a week after surgery. No fever, incision infection, umbilical hemia, peritonitis, and ascites were reported. The clear-liquid diet was recommended for one day after operation, and postoperative activity was allowed since the second day after operation. All patients were discharged on the fourth or fifth day, and all recovered to their normal life at one week after discharge. Follow-up showed that the scar was small and hidden in umbilical without visible incision after one month. Ultrasonic examination results showed that gallbladder contractile function worked perfectly in four patients and no gallbladder stone was found after three months. Conclusion Gallbladder-preserving cholelithotomy by natural orifice transumbilical endoscopic surgery is a safe and effective option for patients with cholecystolithiasis, provides excellent cosmetic outcomes, and can be appropriately carried out under the strict control of surgical indications.