OBJECTIVE To explore the independent risk factors of voriconazole （VCZ）-related liver injury in elderly patients with hypoproteinemia. METHODS Elderly patients with invasive fungal infection and hypoproteinemia who were hospitalized in the respiratory intensive care unit of our hospital and treated with VCZ from August 2020 to July 2023 were selected. They were divided into group A （liver injury group） and group B （non-liver injury group） based on whether the liver injury occurred after using VCZ. Pearson correlation analysis was used to analyze the correlation between minimum concentration （cmin） of VCZ and inflammatory factor[C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）]， as well as liver function [alanine transaminase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBIL）]； univariate analysis was performed by using χ 2 test； Logistic regression analysis was used to analyze the independent risk factors affecting the occurrence of liver injury. RESULTS A total of 320 patients were included in the study， of whom 56 developed liver injury， with an incidence of 17.50%. The VCZ cmin in group A was significantly higher than group B （P＝ 0.021）. CRP， PCT， IL-6， and TBIL were correlated with VCZ cmin （P＜0.05）. CRP， PCT， IL-6， and TBIL had a significant impact on VCZ cmin （P＜0.05）. VCZ cmin， PCT， and TBIL were independent risk factors for liver injury （P＜0.05）. The patients with VCZ cmin≥3.76 mg/L had a significantly increased risk of liver injury. CONCLUSIONS VCZ cmin， PCT， and TBIL are independent risk factors for the occurrence of liver injury in elderly patients with hypoproteinemia. For patients with high PCT and TBIL， VCZ cmin and liver function should be closely monitored during VCZ treatment to reduce the risk of liver injury.

Objective:To investigate the changes of thyroid hormones and the flow velocity of superior thyroid artery in patients with Graves' disease and Hashimoto's thyrotoxicosis before and after treatment with methimazole.Methods:A case-control study was conducted to select 45 cases of Graves' disease and 45 cases of Hashimoto's thyroiditis from October 2021 to December 2022 in the Department of Endocrinology, North China University of Science and Technology Affiliated Hospital. The changes of thyroid hormone and blood flow velocity of superior thyroid artery in patients with Graves' disease and Hashimoto's thyroiditis before and after treatment with methimazole were analyzed. Measurement data satisfying normal distribution were expressed by xˉ±s, and the mean between two groups was compared by t test. Measurement data not satisfying normal distribution were expressed by M( Q1, Q3), and the median between two groups was compared by Wilcoxon rank sum test. χ 2 test was used to compare the constituent ratio of enumeration data among groups. Results:There was no significant difference in thyroid stimulating hormone (TSH) between the two groups before treatment, and there was no significant difference in TSH between the two groups after 1 month and 3 months of treatment (all P>0.05). The levels of free triiodothyronine (FT3) were (24.09±9.29) pmol/L and (17.41±9.36) pmol/L in Graves' disease group and Hashimoto's thyroiditis group respectively before treatment. FT4 were (60.23±20.82) and (43.47±21.71) pmol/L, respectively, and the peak stolie vloiy (PSV) were (69.53±5.70) and (52.65±4.64) cm/s, respectively in Graves' disease group and Hashimoto's thyroiditis group respectively before treatment. There were significant differences between the two groups ( t values wrere 3.39 and 3.74, Z=13.83, all P<0.001). The difference of FT3 between one month after treatment and before treatment was (-6.36±5.32) and (-12.64±9.08) pmol/L ( t=4.02, P<0.001) and the difference in FT3 between 3 months of treatment and before treatment was (-10.14±9.50) and (-17.80±11.17) pmol/L, respectively ( t=3.51, P<0.001) between the Graves disease group and the Hashimoto's thyroiditis group. The difference in FT4 between the Graves disease group and the Hashimoto's thyroiditis group after 1 month of treatment and before treatment was (-28.47±10.09) and (-20.57±14.48) pmol/L ( t=7.01, P<0.001), and the difference of FT4 was (-47.06±20.57) and (-30.17±20.54) pmol/L ( t=3.91, P<0.001) between the Graves disease group and the Hashimoto toxin group. The difference between one month after treatment and before treatment was (-13.10(-34.10,-2.60)) and (-10.50(-27.5,-0.20)) cm/s ( Z=2.63, P=0.009), respectively. The difference between 3 months and before treatment was (-31.40(-53.20,-12.70)) and (-19.90(-46.00,-4.70)cm/s ( Z=4.40, P<0.001)) between the Graves disease group and the Hashimoto's thyroiditis group, and the difference was statistically significant. Conclusion:Thyroid hormone levels were decreased after treatment with methimazole in patients with diffuse toxic goiter and Hashimoto toxemia, but the difference was not statistically significant. The PSV level of superior thyroid artery in patients with diffuse toxic goiter was significantly lower than that in patients with Hashimoto's thyrotoxicosis.

Objective:To analyze the clinical and pathological data of 15 patients with light chain amyloidosis initially diagnosed with other kidney diseases, and identify possible misdiagnosis reasons.Methods:It was a retrospective observational study. The clinical and pathological data of 15 patients, whose initial kidney biopsies failed to diagnose light chain-amyloidosis but were confirmed by a subsequent kidney biopsy or pathology consultation at Peking University First Hospital from January 2010 to December 2022 were collected. The results of immunofluorescence, Congo red staining, and electron microscopy of two renal biopsies were analyzed.Results:The median age of 15 patients was 56 years old, with a male-to-female ratio of 7∶8. The main clinical manifestation was massive proteinuria with normal kidney function, and there were 10 cases presenting as nephrotic syndrome. The initial diagnosis based on the first kidney biopsy included minimal change disease (8 cases), IgA nephropathy (3 cases), membranous nephropathy (3 cases), and type Ⅲ collagen glomerulonephritis (1 case). M proteinemia was not evaluated in 13 patients during the first kidney biopsy. Light chain immunofluorescence staining was not performed in 12 cases. Congo red staining was not performed in 13 cases. All fifteen patients received glucocorticoids combined with immunosuppressive therapy after their initial diagnosis, and 5 patients developed severe infection. After 12.0 (7.5, 20.0) months of treatment, none of them achieved clinical remission. Thirteen had evidences for M protein before the second kidney biopsy. The renal tissues of all patients underwent immunofluorescence light chain examination, Congo red staining, and immunoelectron microscopy examination when necessary. The repeat kidney biopsies of 14 cases and pathology consultation of one case consistently indicated light chain-amyloidosis. The kidney tissues in 13 cases were confirmed to be light chain restricted, 11 cases by immunofluorescence, and 2 cases by immune electron microscopy. After diagnosis of light chain-amyloidosis, all patients received targeted plasma cell therapy except for 1 patient lost to follow-up, 6 patients achieved hematologic remission, 5 patients achieved renal remission, 1 patient entered end-stage renal disease, and 3 patients died.Conclusions:In middle and elderly-aged patients with nephrotic syndrome, if conventional immunosuppressive therapy yields unsatisfactory results, it is crucial to focus on identifying evidences of monoclonal immunoglobulinemia, if necessary, kidney biopsy should be actively repeated. Kidney biopsy pathology should include comprehensive examinations such as light chain immunofluorescence, Congo red staining, and electron microscopy to avoid misdiagnosis of light chain-amyloidosis.

Stroke often causes severe motor, sensory, and daily living function impairments, especially the recovery of distal limb extensor motor function is the most difficult. With the widespread application of Contralateral Control Functional Electrical Stimulation (CCFES) in stroke rehabilitation and continuous improvement of integrated wearable devices in recent years, it has been found that CCFES and combination therapy have good therapeutic effects in improving wrist extension and ankle dorsiflexion function in stroke patients. CCFES can improve both distal and proximal upper limb function, when applied to lower limbs, attention should be paid to the reverse coordination mechanism. Early intervention, sufficient treatment courses, and multiple combination CCFES treatment plans can accelerate the improvement of stroke patients' function.

ObjectiveTo compare the transcriptional levels of two cultivars （Mingui 1 and Mingui 2） with different stem and leaf colors. MethodThe fresh leaves with petioles and the upper stems from Angelica sinensis with two colors were selected as the material， and the hybrid sequencing strategy was used. The technology at the transcriptome was used to build the non-reference full-length transcript library of A. sinensis， and the RNA-seq technology was used to analyze differentially expressed genes of the two cultivars， reusing a public database for biology function annotation and fine classification of differentially expressed genes. The main candidate genes regulating color differences between stems and leaves of A. sinensis were screened out. ResultThe sequencing results of A. sinensis transcripts were good and the quality of the sequencing data was high. The 34 528 full-length transcripts were annotated into 33 947， 33 241， 29 150， and 22 601 in the Non-redundant Protein Sequence Database （NR）， Kyoto Encyclopedia of Genes and Genomes （KEGG）， SwissProt， and Clusters of Orthologous Groups for Eukaryotic Complete Genomes （KOG）， respectively. The 705 differentially expressed genes of the two cultivars with biological and molecular functions were divided into 11 categories， which were mainly enriched in the primary metabolism （17.87%）， stress response （14.47%）， and secondary metabolism （11.49%）. The differentially expressed genes related to colors were mainly concentrated in the flavonoid biosynthesis pathway. ConclusionThe main reason for the color differences of the stems and leaves in two cultivars of A. sinensis may be related to the expression differences of genes regulating flavonoid biosynthesis， which lays a foundation for subsequent functional verification and further clarification of the relationship with the main pharmacodynamic components of A. sinensis.

With the continuous development of traditional Chinese medicine （TCM）， the requirement for the quality of Chinese medicines has become increasingly higher since they have been widely used in clinical practice. Chinese medicinal materials are the material basis for the inheritance and development of TCM， and their quality directly affects the clinical efficacy. Studying the quality of Chinese medicinal materials is the key to ensure the quality and realize the large-scale application. As one of rare Chinese medicinal materials， Cistanches Herba has the functions of tonifying kidney yang， invigorating blood and essence， moistening intestines to relieve constipation. High-quality Cistanches Herba is characterized by glossy appearance， high density， fleshy and soft texture， and sweet taste. With the reduction of wild resources， the products from cultivated Cistanche deserticola or C. tubulosa become dominant on the market of Cistanches Herba. The cultivation areas are widely distributed， mainly concentrated in Gansu， Inner Mongolia， and Xinjiang. However， the cultivated products have varied quality due to the differences in germplasm， producing region， cultivation method， harvesting， and processing. According to the theories of quality evaluation based on morphological characteristics and excellent appearance indicating high quality， this paper reviewed the literature on the quality evaluation， growth， development， and processing of Cistanches Herba in the last decade to explore the main factors （genetic characteristics， environmental conditions， and harvesting and processing factors） affecting the quality of Cistanches Herba. The review aims to explore the factors for the high quality and provide a reference for the producing region screening， directional cultivation， and production of Cistanches Herba.

ObjectiveTo analyze the sequence variation and genetic diversity of 47 Isatis indigotica germplasm materials， and carry out the study on the genetic differentiation and structure. MethodGenomic DNA of 47 I. indigotica germplasm materials were extracted by kit extraction method. Two chloroplast DNA （cp DNA） sequences and five inter-simple sequence repeat （ISSR） primers were used for amplification and sequencing. Chromas， Mega 7.0， DanSP5， and GenALEx were used to calibrate， splice， and analyze the sequence characteristics. PERMUT and PopGen 1.31 were used to analyze the genetic diversity parameters and genetic structure， and NTSYS was used to obtain the unweighted pair-group method with arithmetic means（UPGMA） clustering tree plot of 47 I. indigotica germplasm materials. ResultA total of 129 samples from 47 I. indigotica germplasm materials were successfully amplified and sequenced. The length of 2 cp DNA sequences after spliced was 1 412 bp， and there were 377 polymorphic variation loci， and 36 haplotypes. Fu and Li's D* test was significant （P<0.01）. The values of Pi， H_S， and H_T based on cp DNA were 0.119 89， 0.787， and 0.891， respectively. The genetic differentiation coefficients of gene differentiation coefficient（Gst）， nucleotide differentiation coefficient（Nst）， and fixation index（Fst） were 0.117， 0.468， and 0.488， respectively， and the gene flow （Nm） was 0.615. The mean values of PPB， Shannon information diversity index（I）， Nei's genetic diversity index（H）， and Gst based on ISSR were 78.85%， 0.334 8， 0.218 6， and 0.754 4， respectively， and the Nm value was 0.162 8. ConclusionI. indigotica has high genetic diversity and abundant haplotypes at the species level， with abundant haplotypes. Genetic differentiation among different germplasm materials is obvious， and gene exchange is not frequent. Genetic variation mainly exists among populations. The population has accumulated various low-frequency gene mutations recently， suggesting that it has experienced significant regional expansion in the history.

ObjectiveTo conduct genetic variation analysis of 11 cultivars and 7 wild populations of Angelica sinensis in Gansu province based on the chloroplast gene （cp DNA）， and provide references for germplasm identification and breeding of new cultivars of A. sinensis. MethodThree pairs of cp DNA primers were used for polymerase chain reaction （PCR） amplification and sequencing of A. sinensis samples. MegaX was used to perform statistics on sequence characteristics and calculate mean genetic distances among A. sinensis populations. Unweighted pair-group method with arithmetic means （UPGMA） clustering tree based on genetic distance was constructed by NTSYS 2.10e. DanSP v6 was used to calculate sequence polymorphism and Tajima's D of A. sinensis. PERMUT was used to calculate the population structure of A. sinensis. Arlequin v3.5 was used to perform molecular variation analysis， and PopART1.7 was used to construct TCS haplotype network. ResultThree pairs of cp DNA primers were amplified， sequenced， compared， and combined to give a sequence length of 1 759 bp. One variable site was detected in the wild A. sinensis and 480 variable sites were detected in the cultivated A. sinensis， including 97 singleton variable sites， 383 parsimony informative sites， and 152 insertion-deletion sites. In the three regions of matK， psbA-trnH， and rbcL of cp DNA in the wild and cultivated A. sinensis， matK was the region with the highest polymorphism. Tajima’s D of all the combined sequences of A. sinensis were not significantly negative， but psbA-trnH and rbcL genes of the cultivated A. sinensis were significantly negative， indicating that the A. sinensis followed neutral evolution on a whole， while psbA-trnH and rbcL genes had undergone selection. The degree of genetic differentiation （Fst=0） among wild populations was lower than that among cultivated populations （Fst=0.114 19， P<0.05）. The degree of genetic differentiation between wild and cultivated A. sinensis was relatively high （Fst=0.942 55， P<0.01）. Genetic variation in the cultivated A. sinensis was mainly found within the populations （89%）. UPGMA cluster tree based on genetic distance showed that the wild A. sinensis and the cultivated A. sinensis were clustered into one branch， respectively， with a distant genetic relationship， and the population 3 in the cultivated A. sinensis was far from other cultivated populations. The TCS haplotype network consisted of 15 haplotypes and 4 unknown haplotypes， which was divided into 3 parts， with a large number of variations among each part. Shared haplotypes were only found in the wild or cultivated groups， and there were no shared haplotypes between groups. ConclusionThe genetic diversity of A. sinensis was low at species level， and the population diversity of the wild was lower than that of the cultivated. The degree of genetic differentiation between the wild and the cultivated A. sinensis was high， but that in the wild and the cultivated populations were low. Genetic variation in the cultivated A. sinensis was mainly found within populations.

Objective:To evaluate the efficacy and safety of perioperative rehabilitation approaches based on the concept of Enhanced Recovery After Surgery (ERAS) for pelvic fractures.Methods:A prospective randomized control trial was conducted to include 114 emergency patients who had been admitted to Department of Orthopaedic Trauma, Beijing Jishuitan Hospital for surgical treatment of pelvic fractures from June 2019 to December 2020. Of them, 57 were assigned into an intervention group according to a random digits table. They were 42 males and 15 females, aged from 18 to 77 years and subjected to management of pelvic fractures with tentative perioperative ERAS approaches which were adjusted at different stages. The other random 57 patients were assigned into a control group. They were 40 males and 17 females, aged from 17 to 70 years and subjected to management of pelvic fractures with conventional rehabilitation approaches which included postoperative in-hospital consultation and guidance by rehabilitation physicians. The 2 groups were compared in terms of Majeed pelvis scores and Barthel indexes at postoperative 2, 6, 12 and 24 weeks, and visual analogue scale (VAS) pain scores and SF36 scores at postoperative 12 and 24 weeks.Results:A total of 105 patients (55 in the intervention group and 50 in the control group) were completely followed up for 151 to 254 d (mean, 177 d). The 2 groups were comparable due to no significant difference between them in the preoperative general data ( P>0.05). The Majeed scores (44±13, 67±16, 86±14 and 98±7) and Barthel indexes (57±13, 79±16, 95±8 and 100±2) at postoperative 2, 6, 12 and 24 weeks in the intervention group were significantly higher than those in the control group [(35±16, 51±16, 73±14 and 91±12) and (45±19, 67±18, 86±12 and 98±4)] (all P<0.05). At postoperative 12 and 24 weeks, the SF-36 scores (129±15 and 141±6) in the intervention group were significantly higher than those in the control group (114±15 and 131±12) ( P<0.05). There was no significant difference in the pain degree between the 2 groups ( P>0.05). Conclusion:In management of pelvic fractures, compared with conventional perioperative rehabilitation approaches, the perioperative ERAS rehabilitation approaches may improve early functional outcomes and thus help the patients restore their activities of daily living earlier.

Objective:To explore the relationship between expression levels of CLOCK mRNA and protein and the clinical characteristics of patients with nasopharyngeal carcinoma.Methods:The frozen tissue specimens from 33 patients with nasopharyngeal carcinoma in the Affiliated Tumor Hospital of Guizhou Medical University from 2018 to 2019 were collected. Seventeen cases of tissue specimens from patients with nasopharyngeal chronic inflammation in the Affiliated Hospital of Guizhou Medical University in 2019 were collected. From 2008 to 2014, 68 cases of formalin-fixed paraffin-embedding (FFPE) nasopharyngeal carcinoma tissue and 37 cases of FFPE nasopharyngeal chronic inflammation tissue were collected from the Affiliated Tumor Hospital of Guizhou Medical University. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were used to detect the mRNA and protein expression levels of CLOCK. The nasopharyngeal carcinoma cells including CNE1, CNE2, 5-8F and the normal nasopharyngeal epithelial cell NP69 were cultured. qRT-PCR was used to detect the expression level of CLOCK mRNA in each cell line at the time points of ZT2, ZT6, ZT10, ZT14, ZT18 and ZT22. The cosine method was used to fit the rhythm of CLOCK gene in nasopharyngeal carcinoma. The protein expression of CLOCK protein was detected by using immunohistochemical method in 68 cases of nasopharyngeal carcinoma and 37 cases of nasopharyngeal chronic inflammation tissue. Survival was analyzed by Kaplan-Meier method and Log rank test, and the influencing factors was analyzed by Cox regression model.Results:The expression levels of CLOCK mRNA in CNE1, CNE2 and 5-8F cells (0.63±0.07, 0.91±0.02 and 0.33±0.04, respectively) were lower than that in NP69 cell (1.00±0.00, P<0.05). The expression levels of CLOCK protein in CNE1, CNE2 and 5-8F cells (0.79±0.06, 0.57±0.05 and 0.74±0.10, respectively) were lower than that of NP69 cells (1.00±0.00, P<0.05). The expressions of CLOCK mRNA in nasopharyngeal carcinoma cells including CEN1, CNE2, 5-8F and normal nasopharyngeal epithelial cell NP69 were different at different time points, with temporal fluctuations. The fluctuation periods of CLOCK mRNA in CNE1, CNE2, 5-8F, and NP69 cells were 16, 14, 22 and 24 hours, respectively. The peak and trough times were ZT10: 40 and ZT18: 40, ZT10 and ZT3, ZT14: 30 and ZT3: 30, ZT12: 39 and ZT0: 39, respectively. CLOCK mRNA and protein expression levels in nasopharyngeal carcinoma tissues (0.37±0.20 and 0.20±0.26, respectively) were lower than those in nasopharyngeal chronic inflammation tissues (1.00±0.00 and 0.51±0.41, respectively, P<0.05). The 1, 3, and 5-year survival rates of patients in the CLOCK protein high expression group (CLOCK protein expression level ≥ 0.178) were 96.2%, 92.1%, and 80.1%, respectively, which were higher than those in the low expression group (CLOCK protein expression level <0.178, 92.9% , 78.6% and 57.1%, respectively, P=0.009). The 1, 3, and 5-year progression-free survival (PFS) rates of patients in the CLOCK protein high expression group were 96.2%, 87.8%, and 87.7%, respectively, which were higher than those in the low expression group (92.7%, 82.2%, and 70.8%, respectively, P=0.105). Compared with the low-expression group (100.0%, 96.9%, and 90.0%, respectively), the 1, 3, and 5-year recurrence-free survival rates of patients in the CLOCK protein high expression group (100.0%, 95.7%, and 95.7%, respectively) were not statistically significant ( P=0.514). Compared with the low-expression group (92.7%, 82.2%, and 79.3%), the 1, 3, and 5-year survival rates without metastasis in the CLOCK protein high expression group (96.2%, 92.0%, and 92.0%, respectively) were not statistically significant ( P=0.136). CLOCK protein expression and T stage were independent prognostic factors of overall survival ( P<0.05). Conclusions:The expression of CLCOK is downregulated in the nasopharyngeal carcinoma cell and nasopharyngeal carcinoma tissues. Clock gene CLOCK is rhythmically expressed in the nasopharyngeal carcinoma cells and normal nasopharyngeal epithelial cells. Compared with normal nasopharyngeal epithelial cells, the fluctuation period of CLOCK in nasopharyngeal carcinoma cells is shortened. The overall survival of patients in the CLOCK protein high expression group is better than that of low expression group. The expression of CLOCK protein is an independent influencing factor for overall survival. CLOCK gene may be a potential tumor suppressor gene in the nasopharyngeal carcinoma.