OBJECTIVE To investigate the efficacy and safety of hepatic arterial infusion chemotherapy based on the oxaliplatin and fluorouracil drug combination （HAIC-FOLFOX） combined with camrelizumab in the treatment of unresectable hepatocellular carcinoma （HCC）. METHODS The data of 222 unresectable HCC patients hospitalized at Liaoning Cancer Hospital & Institute from January 1， 2021 to March 1， 2023 were retrospectively collected. Based on treatment regimens， patients were divided into a control group （HAIC-FOLFOX+sorafenib， n＝117） and an observation group （HAIC-FOLFOX+camrelizumab， n＝ 105）. Short-term efficacy indicators [objective remission rate （ORR） and disease control rate （DCR）] and long-term efficacy indicators [median overall survival （mOS） and median progression-free survival （mPFS） within one year] after 4 cycles of treatment， the levels of tumor markers （alpha fetoprotein， carcinoembryonic antigen， carbohydrate antigen 19-9）， immune function indicators （CD3+， CD4+， and CD8+ T-cell subsets） before treatment and after 4 cycles of treatment， as well as the occurrence of adverse reactions， were compared between two groups. RESULTS The ORR of the observation group was 55.24%， which was significantly higher than 35.90% of the control group （P＜0.05）； while there was no statistically significant difference in DCR between the two groups （P＞0.05）. The mOS and mPFS within 1 year of the observation group （15.33， 10.83 months） were significantly longer than the control group （11.34， 8.04 months） （P＜0.05）. After 4 cycles of treatment， tumor marker levels of the two groups were significantly lower than before treatment， and the proportions of CD3+ and CD4+ T cells were significantly higher than before treatment （P＜0.05）. Above indexes of the observation group were significantly better than the control group at the same time （P＜0.05）. The proportions of patients in the observation group who developed grade 1-3 immune-related pneumonia and capillary proliferation were significantly higher than the control group （P＜0.05）， while there were no statistically significant differences in the proportions of patients experiencing grade 1-3 adverse reactions such as fever， fatigue and rash between two groups （P＞0.05）. CONCLUSIONS Compared with HAIC-FOLFOX combined with sorafenib， HAIC-FOLFOX combined with camrelizumab can significantly improve the ORR， prolong mOS and mPFS within 1 year， effectively reduce tumor marker levels， and improve certain immune function indicators in patients with unresectable HCC， but it increases the risk of immune-related adverse events.

ObjectiveUltra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS/MS） was used to investigate the metabolism and distribution of nardosinone in rats， then metabolic pathways were speculated. MethodRats were administered with 30 mg·kg^-1 of nardosinone suspension by gavage for 3 consecutive days， and plasma， urine， feces， and tissues of heart， liver， spleen， lung， kidney， brain， stomach， and intestine were collected at predetermined time points. After treatment， the samples were processed for UPLC-Q-Exactive Orbitrap MS/MS， and the MS data were analyzed using Xcalibur 2.2 software. The metabolites were searched by comparing the base peak chromatogram and extracted ion chromatogram between the treated group and blank group， and based on the relative retention time（t_R）， quasi-molecular ion peak， precise molecular mass， and fragment ions of MS/MS， the elemental composition were searched using databases such as SciFinder and PubChem， as well as referring to relevant literature， the possible metabolites were identified and the metabolic pathways were inferred. ResultA total of 30 metabolites of nardosinone were identified， including 15， 19， 12， 7， 4， 11， 8， 13， 13， 8 and 12 metabolites in urine， feces， plasma， brain， heart， liver， spleen， lung， kidney， stomach and intestine， respectively. The main metabolic pathways of nardosinone in rats were hydroxylation， dehydroxylation， reduction， dehydrogenation， hydration， dehydration， carboxylation， glucuronidation， and dehydroxy-isopropyl. ConclusionNardosinone can be metabolized by phase Ⅰ and phase Ⅱ metabolism in rats， and the metabolites are widely distributed in the major organs. The results of this study can provide a basis for further research on the pharmacodynamic material basis， pharmacological mechanism and clinical application of nardosinone.

Objective To compare the efficacy of ultrasound-guided microwave ablation versus thyroidectomy in the treatment of benign thyroid nodules (BTN) and to explore the influencing factors of prognosis. Methods A total of 282 BTN patients were enrolled and divided into ablation group (treated with ultrasound-guided microwave ablation, n=172) and resection group (treated with thyroidectomy, n=110) based on treatment methods. Perioperative indicators and thyroid function indices before and after surgery were compared between the two groups. Patients were followed up for 1 year and divided into good prognosis group [volume reduction rate (VRR)≥80%, n=210] and a poor prognosis group (VRR < 80%, n=72) based on the VRR. Factors influencing the prognosis of BTN patients were analyzed. Results The ablation group had shorter operative time and hospital stay, less intraoperative blood loss, and lower postoperative Visual Analogue Scale (VAS) scores compared to the resection group (P < 0.05). One month after surgery, serum thyrotropin (TSH) levels were higher, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were lower than preoperative levels in both groups, however, TSH level was lower, and FT3 and FT4 levels were higher in the ablation group compared to the resection group (P < 0.05). Univariate analysis showed that preoperative TSH levels, the proportion of solid nodules, and the proportion of nodules in the risk zone were lower, while preoperative FT4 levels were higher in the good prognosis group compared to the poor prognosis group (P < 0.05). Binary Logistic regression analysis revealed that nodule type, nodule location, preoperative TSH, and preoperative FT4 were all influencing factors for the prognosis of BTN patients (P < 0.05). Conclusion Compared to thyroidectomy, ultrasound-guided microwave ablation for BTN offers advantages such as less intraoperative blood loss, milder postoperative pain, shorter operative time and hospital stay, and less damage to thyroid function. Preoperative TSH and FT4 levels, nodule type, and nodule location are closely related to the prognosis of BTN patients and should be given attention in clinical practice.

Objective:To investigate the clinicopathologic features and differential diagnosis of ureteral fibroepithelial polyps.Methods:The clinicopathologic features and prognosis of ureteral fibroepithelial polyps with complete data retrieved from the pathology database of the Institute of Urology, Peking University from January 2013 to December 2021 were collected and analyzed. All HE staining sections were reviewed by a senior urologic pathologist. Immunohistochemical analysis was done in some cases for differential diagnosis. The clinical, imaging and outcome data were collected, and discussed together with relevant literature.Results:There were 45 patients with complete clinicopathologic data, including 34 males and 11 females (male: female=3.1∶1.0), with a median age of 36 (range 13-80) years. Preoperative diagnosis included polyp in 23 cases, tumor in 19 cases and calculi in 3 cases. The main clinical symptoms were hematuria (13 cases), low back and abdominal pain (9 cases) and no symptoms (9 cases). There were 29 cases of multiple polyps, 16 cases of single polyp; 32 cases were on the left side, 13 cases were on the right side; 29 cases of upper polyps, 9 cases of middle polyps, and 6 cases of lower polyps. Twenty-seven patients had no related urologic history, 10 patients had history of urolithiasis, and the rest had history of stents, strictures or tumors. Local ureteral resection and anastomosis were the most common treatment (20 cases), followed by ureteroscopic polypectomy (12 cases). The patients were followed up from the pathological diagnosis to the cut-off time: 4 cases were lost to follow-up, and the remaining 34 cases were followed up for 3 to 85 (mean 60 months). One case had polyp recurrence after 3 months, and the other case had polyp recurrence after 2 years. Fibroepithelial polyps had a variety of gross manifestations, ranging from elongated polyps or small papillary and polypoid to large papillary masses. Microscopically, they were divided into type 1, type 2 and type 3, and the type 3 was the most common type (28 cases). In this study, there were 41 cases of simple fibroepithelial polyp, 2 cases of malignant transformation of polyps into urothelial carcinoma, one case of polyps with urothelial carcinoma, and one case of polyp with surface urothelial carcinoma in situ; the stroma showed myofibroblastic proliferation.Conclusions:The clinical manifestations and morphologic characteristics of ureteral fibroepithelial polyps are diverse. The three microscopic types are easily confused with many benign and malignant ureteral diseases, such as inflammatory polyps, adenocystitis, papilloma, etc. Awareness of the key differentiation points and judicious use of immunohistochemistry will be helpful for the diagnosis and differential diagnosis.

Objective:To learn about the status of iodine deficiency disorders (IDD) in Zhumadian City, Henan Province, and to provide basis for scientific intervention measures.Methods:From 2016 to 2020, monitoring sites were set up in nine counties (districts) of Zhumadian City, and a town/street was selected from each of the five directions of East, West, South, North and Middle at each monitoring site. One primary school was selected from each town/street, 40 non-boarding children aged 8-10 years were selected from each primary school (half male and half female). In addition, 20 pregnant women were selected from each town/street. Urine samples and edible salt samples at home were collected from these children and pregnant women for iodine determination. Some children and pregnant women were selected to investigate the awareness rate of IDD prevention and treatment knowledge. Thyroid B-ultrasound examination was performed in some children. Iodine in drinking water was determined according to the national and provincial requirements of "strengthening scientific iodine supplementation".Results:From 2016 to 2020, a total of 13 500 salt samples were tested, including 12 453 qualified iodized salt samples and 246 non-iodized salt samples. The qualified iodized salt consumption rates of children and pregnant women were 92.26% (8 303/9 000) and 92.22% (4 150/4 500), respectively, and the non iodized salt consumption rates were 1.89% (170/9 000) and 1.69% (76/4 500), respectively. The median urinary iodine concentration of children were 208.91, 179.02, 222.85, 203.50 and 230.50 μg/L, respectively. The median urinary iodine concentration of pregnant women were 182.01, 153.26, 178.72, 196.82 and 178.75 μg/L, respectively. The goiter rate in children was 1.63% (49/3 000), there was no significant difference between different age groups (χ 2 = 0.47, P = 0.790), and between different genders (χ 2 = 0.01, P = 0.912). The awareness rate of IDD prevention and treatment knowledge was 94.68% (11 916/12 585) in children and 91.75% (4 537/4 945) in pregnant women. A total of 27 664 water samples were collected from 1 572 administrative villages, with a median of 12.90 μg/L of water iodine, including 1 383 low-iodine villages, 173 moderately iodine villages and 16 high-iodine villages. Conclusions:Children's iodine nutrition exceeds the appropriate amount, and pregnant women's iodine nutrition is appropriate in Zhumadian City Henan Province. In combination with the results of water iodine monitoring, we will continue to carry out IDD monitoring and consolidate the results of prevention and control.

Although chromosomal mosaic embryos detected by trophectoderm(TE)biopsy offer healthy embryos available for transfer,high-resolution postnatal karyotyping and chromosome testing of the transferred embryos are insufficient.Here,we applied single-cell multi-omics sequenc-ing for seven infants with blastula chromosomal mosaicism detected by TE biopsy.The chromo-some ploidy was examined by single-cell genome analysis,with the cellular identity being identified by single-cell transcriptome analysis.A total of 1616 peripheral leukocytes from seven infants with embryonic chromosomal mosaicism and three control ones with euploid TE biopsy were analyzed.A small number of blood cells showed copy number alterations(CNAs)on seem-ingly random locations at a frequency of 0％-2.5％per infant.However,none of the cells showed CNAs that were the same as those of the corresponding TE biopsies.The blastula chromosomal mosaicism may be fully self-corrected,probably through the selective loss of the aneuploid cells dur-ing development,and the transferred embryos can be born as euploid infants without mosaic CNAs corresponding to the TE biopsies.The results provide a new reference for the evaluations of trans-ferring chromosomal mosaic embryos in certain situations.

ObjectiveTo investigate the features and changing trend of drug-induced liver injury (DILI) in the elderly from 2009 to 2019, and to provide a reference for clinical prevention and treatment of DILI in the elderly. MethodsA retrospective analysis was performed for the clinical data of 2107 elderly patients, aged ≥60 years, who were diagnosed with DILI in The Fifth Medical Center of Chinese PLA General Hospital from January 2009 to December 2019, and they were divided into groups according to age. Related clinical data were analyzed, including age, sex, clinical features, prognosis, and regional distribution. The Chi-square test was used for comparison of categorical data between groups. ResultsAmong the 2107 patients with DILI, there were 802 male patients and 1305 female patients, with a male/female ratio of 1∶1.63. Cholestasis type was the most common clinical type and was observed in 1439 patients (68.3%). There was the highest number of patients in the 60-64 years group (942 patients, 44.7%), among whom 618(65.6%) were female, 589(62.5%) had cholestasis type, 471(50.0%) had chronic DILI, 421(44.7%) had drug-induced liver cirrhosis, and 25(2.7%) had drug-induced liver failure. There were 187 patients in the 75-79 years group, among whom 110 (58.8%) patients were male, 137(73.3%) had cholestasis type, 114(60.9%) had liver cirrhosis, 4(2.1%) had drug-induced liver failure. The results showed that chronic DILI was more common in the 60-64 years group, and liver cirrhosis was more common in the 75-79 years group. As for prognosis, in the 60-64 years group, 27 patients (2.9%) were cured, 885 (93.9%) were improved, 30(32%) had no response or died; in the 65-69 years group, 16 (2.8%) were cured, 528 (92.0%) were improved, and 30(5.2%) had no response or died; in the 70-74 years group, 9(2.8%) were cured, 305(94.1%) were improved, and 10 (3.6%) had no response or died. The results showed that there was no significant difference in mortality rate between the different age groups (P＞0.05). The proportion of elderly DILI patients among hospitalized DILI patients increased from 15.90% in 2009 to 22.05% in 2013 and 27.51% in 2019, with a 1.73-fold increase in 11 years. As for regional distribution, the patients in North China accounted for the highest proportion of 47.08% (the patients from Hebei, Shanxi, and Inner Mongolia accounted for 24.92%, 10.96%, and 10.25%, respectively), followed by those in Northeast China who accounted for 17.85%. The patients in Beijing accounted for 11.53%. ConclusionThe proportion of elderly DILI patients among hospitalized DILI patients tends to increase in these years. Cholestasis type is the most common clinical type, and most of the patients with this clinical type progress to chronic DILI and drug-induced liver cirrhosis. Early diagnosis, early intervention, and standardized treatment of elderly DILI should be taken seriously.

ObjectiveTo investigate the clinical features of patients with Caroli disease. MethodsThe clinical data were collected from 41 patients who were diagnosed with Caroli disease in The Fifth Medical Center of Chinese PLA General Hospital from April 2015 to January 2020, and the patients were divided into type I group with 16 patients and type Ⅱ group with 25 patients. A retrospective analysis was performed for general information, laboratory markers, and clinical features. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data; a Spearman correlation analysis was also performed. ResultsThe type Ⅰ group had a significantly higher level of albumin (Alb) than the type Ⅱ group (t=0.976, P=0.048), and the type Ⅱ group had a significantly higher prothrombin time (PT) than the type I group (Z=3.115, P=0.001). Compared with the type I group, the type Ⅱ group had significantly higher incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (χ2=6.077, 5.468, and 2.403, P=0.002, 0.019, and 0.028). In the patients with type Ⅱ Caroli disease, the level of cholinesterase was negatively correlated with the incidence rates of esophageal and gastric varices and portal hypertension (r=-0.468 and -0.436, P=0.018 and 0.029); Alb level was negatively correlated with the incidence rate of esophageal and gastric varices (r=-0.561, P=0.004); red blood cell count was negatively correlated with the incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (r=-0.662, -0.566, and -0.436, P＜0.001, P=0.003, and P=0.029); hemoglobin count was negatively correlated with the incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (r=-0.605, -0.590, and -0.510, P=0.001, 0.002, and 0.009); PT was positively correlated with the incidence rates of esophageal varices and portal hypertension (r=0.488 and 0.520, P=0.013 and 0.008). ConclusionCompared with the patients with type I Caroli disease, the patients with type Ⅱ Caroli disease have a higher incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension, with the changes in clinical indicators such as the decrease of Alb level and the increase of PT level, and they tend to have poor prognosis.

Objective:To summarize the common sites of osteophytes in patients with hand osteoarthritis (OA), and analyze the correlation between the severity of osteophytes and clinical factors.Methods:One hundred and four patients with hand OA were selected and divided into three groups according to the disease duration: <1 year, 1~5 years, >5 years. The first carpometacarpal joint(CMC1), metacarpophalangeal joint(MCP), proximal interphalangeal joint (PIP) and distal interphalangeal joint (DIP) were detected by high fre- quency ultrasound. The location of osteophytes and osteophyte semi-quantitative grading scores (OSGS) were recorded. The patients age, disease duration, erythrocyte sedimentation rate (ESR), C-reactionprotein (CRP), the visual analogy score (VAS) and Australian/Canadian osteoarthrits hand index (AUSCAN) were collected. The indicators of different groups were compared, the incidence and location of osteophytes was calculated, and the correlation between osteophytes and clinical factors was analyzed. Data were analyzed by Wilcoxon rank sum test, Kruskal-Wallis test, χ2 test, Spearman correlation analysis. Results:① Osteophytes accounted for 33.56%(1 047/3 120) of the 3 120 joints in hands. There were statistically significant differences in OSGS and AUSCAN in different groups ( H=13.485, P<0.01; H=51.491, P<0.01), while no statistically difference in VAS, ESR and CRP ( H=5.808, P=0.055; H=2.878, P=0.237; H=2.319, P=0.314). ② In different joint areas of hands, PIP accounted for the largest proportion (46.54%, 484/1 040), followed by DIP (46.51%, 387/832), CMC1 (30.77%, 64/208), and MCP accounted for the smallest proportion(10.77%, 112/1 040). There were statistically significant differences in the incidence of osteophytes in different joint areas( χ2=384.194, P<0.01).③ In the interphalangeal joint areas of hands, the largest osteophytes composition ratio was MCP3 (46.43%, 52/112), PIP3 (30.58%, 148/484) and DIP2 (31.01%, 120/387), respectively. ④ OSGS were positively associated with age, disease course, VAS and AUSCAN ( r=0.370, P<0.01; r=0.382, P<0.01; r=0.215, P=0.029; r=0.390; P<0.01), there was no correlation between OSGS and ESR or CRP ( r=0.173, P=0.079; r=0.162, P=0.101). Conclusion:PIP are the most common sites of osteo-phytes in hand OA, followed by DIP. High frequency ultrasound can help the diagnosis and evaluate the severity of hand OA.

Objective: To establish a mouse model of psoriasis complicated by bone loss by long-term topical application of imiquimod. Methods: Twelve 10-week-old Kunming mice were randomly and equally divided into 2 groups: experimental group topically treated with 50 mg/d imiquimod cream every day on the shaved back, and control group topically treated with equivalent vaseline ointment every day on the shaved back. Skin manifestations were observed on the mouse back every day. The mice were sacrificed 10 weeks later. Before the sacrifice, the degree of erythema, scaling and skin thickening was evaluated, psoriasis area severity index (PASI) was calculated, mouse weight was measured, and eyeball blood was obtained. After the sacrifice, skin lesions on the back were resected and subjected to hematoxylin-eosin staining, so as to evaluate histological changes. Then, the left tibia was obtained from the mice, immunohistochemical staining was performed to observe the expression and distribution of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-β ligand (RANKL) in bone tissues, and micro-computerized tomography was conducted to determine the bone mass of spongy bone, and the bone volume-to-total volume ratio, number, thickness, spacing and connectivity density of the trabecular bone in the proximal tibia. The left femur was also obtained from the mice, and subjected to three-point bending test for evaluating its biomechanical properties. Enzyme-linked immunosorbent assay (ELISA) was performed to detect serum levels of tumor necrosis factor (TNF) -α and interleukin (IL) -17. RNA was extracted from the right tibia, and real-time PCR was conducted to determine the mRNA expression of OPG and RANKL. Two-independent-sample t test was used to compare the above indices between two groups. Results: Ten-week topical stimulation with imiquimod could lead to psoriasiform dermatitis on the mouse back, presenting as erythema, scales and skin thickening. The PASI score was significantly higher in the experimental group (9.167 ± 1.722) than in the control group (0, t = 13.31, P < 0.001) . Hematoxylin-eosin staining showed thickened spinous layer, extended rete ridges, infiltration of inflammatory cells in the superficial dermis, spongiosis, vasodilatation and increased hair follicles in the experimental group. Immunohistochemical staining revealed that the expression of OPG and RANKL was significantly higher in the experimental group (16 021.33 ± 1 954.61, 35 433.33 ± 1 197.95 respectively) than in the control group (3 307.00 ± 1 158.72, 13 644.67 ± 4 764.61, respectively; t = 9.692, 7.682 respectively, both P < 0.01) . Micro-computerized tomography showed that the bone volume-to-total volume ratio and thickness of trabecular bone in the proximal tibia were significantly lower in the experimental group than in the control group, but the spacing of trabecular bone was significantly higher in the experimental group than in the control group (P < 0.01 or < 0.05) . There were no significant differences in the elastic modulus and fracture energy of the femur between the experimental group and control group (both P > 0.05) . Moreover, no significant differences in the serum levels of TNF-α and IL-17 were observed between the two groups (both P > 0.05) . Real-time PCR revealed that the mRNA expression of OPG and RNAKL was significantly higher in the experimental group than in the control group (P < 0.05, < 0.01 respectively) . Conclusions Long-term topical application of imiquimod can not only induce psoriasiform dermatitis in mice, but also lead to bone loss of spongy bone and micro-architectural deterioration in the proximal tibia. Thus, mouse models of psoriasis complicated by bone loss can be established by long-term imiquimod stimulation.