This paper summarizes professor TU Jinwen's clinical experience in treating cancer-related insomnia （CRI） based on different qi and fire. It is believed that the pathogenesis of CRI can be divided into three stages. At the initial stage， qi movement is constrained， while the strong fire begins to stir， and the sovereign fire is unsettled， when qi is abundant， but the fire is not excessive. For this， Sanhua Jieyu Anshen Decoction （三花解郁安神汤） is suggested， which can move qi and vent constraint， clear and diffuse strong fire， calm the heart and spirit. At the progressive stage， strong fire becomes intense and burning， and qi transformation weakens， with toxin fire harassing the spirit. This is the stage where both qi and fire are excessive， for which Huanglian Jiedu Anshen Decoction （黄连解毒安神汤） can be used to clear and dissipate strong fire， drain fire and resolve toxin， clear heart and calm spirit. At the terminal stage， strong fire subsides， and consumption of qi damages healthy qi， with failure of nourishment of heart spirit， when both qi and fire deplete. Correspondingly， Erren Yangxin Anshen Decoction （二仁养心安神汤） is used to boost qi and nourish yin， restore interaction between the heart and the kidney， nourish the heart and calm spirit.

Progressive symmetric erythrokeratodermia(PSEK)is a rare hereditary skin disease charac-terized by symmetrical erythema,hyperkeratosis and multiorgan lesions.Its clinical phenotypes are highly heterogeneous and may be accompanied by symptoms such as thrombocytopenia,which can be fatal in se-vere cases.The genotype-phenotype association mechanism of PSEK is extremely complex.Currently,it is known that mutations in multiple genes such as GJB3,KDSR,and KRT83 can cause the disease.A-mong them,3-ketodihydrosphingosine reductase(KDSR)has been found to harbor nearly 20 clinical mu-tations.These mutations interfere with the de novo ceramide synthesis pathway,disrupt the homeostasis of the skin barrier,and cause platelet production disorders and multi-organ lesions,making it a current research hotspot in the molecular mechanism of PSEK.The pathogenic mutations of KDSR are widely and uniformly distributed throughout the entire protein,rather than being limited to the traditionally recog-nized active center,suggesting that the impairment of the KDSR enzymatic activity is not the only cause of PSEK.In view of this,this study selected four typical mutants of KDSR(KDSRQG55-56R,KDSRn38C,KDSRY186F,KDSRG182S),and first used recombinant expression technology to prepare pure and homoge-neous mutant proteins.Subsequently,thermal stability experiments as well as oligomerization analysis were conducted on these four mutant proteins.The results showed that the Tm values of the four mutants were significantly lower than that of the wild type.Particularly,KDSRF138C and KDSRQG55-56R were nearly completely denatured at physiological temperature.This result was perfectly consistent with the further Rosetta energy analysis.In conclusion,this study took several pathological mutations of the PSEK patho-genic factor KDSR as the research object and discovered that the conformational stability of KDSR might be closely related to the occurrence of PSEK pathogenicity,indicating that the imbalance of conformation-al homeostasis is very likely to be one of the common contributing factors of many genetic diseases,inclu-ding PSEK.This provides a new theoretical basis and reference for explaining the molecular mechanism of genotype-phenotype heterogeneity in many genetic diseases.

Objective:To evaluate the clinical utility of an intelligent endoscope transportation system in the digestive endoscopy center.Methods:A parallel-group controlled trial was conducted at Digestive Endoscopy Center of Qilu Hospital of Shandong University from June 1st to December 31st 2024, comparing robotic intelligent endoscope transport (experimental group) versus manual transport (control group). Performance metrics, including response time, transportation speed, labor efficiency, contamination prevention, closed-loop traceability, and nursing staff satisfaction, were statistically analyzed. Full-time equivalent (FTE) was introduced to quantify the operational efficiency of the experimental group.Results:The study included a total of 60 206 instances of intelligent endoscope transportation and 60 485 instances of manual transportation data. The robotic group demonstrated significantly shorter response times versus manual group for initial dispatch (51.08±14.97 seconds VS 54.44±13.61 seconds, t=35.8, P<0.001) and recovery response time (32.52±11.26 seconds VS 40.20±11.40 seconds, t=103.93, P<0.001). During the 148 days operational period, the success rate was 99.83% (60 104/60 206) and the failure rate was 0.17% (102/60 206) for robotic transports. Primary failure causes were wireless disconnection, pathfinding errors, and mechanical faults, averaging 1.05 malfunctions/month with no adverse events. The success and failure rate was 99.26% (60 043/60 485) and 0.74% (442/60 485) respectively for manual transports. Staff satisfaction was significantly higher for robotic transport in endoscopic transportation (4.65±0.55 scores VS 3.97±0.98 scores, t=96.5, P<0.001) and delivery process (4.71±0.59 scores VS 3.90±1.04 scores, t=210.3, P<0.001). and workload intensity was significantly lower (4.06±0.77 scores VS 4.48±0.63 scores, t=59.9, P=0.025). The system reduced labor requirements by 3.68 FTE, yielding annual savings of ￥657 000. Conclusion:The robotic intelligent endoscope transport system improves work efficiency, reduces nursing labor costs and physical workload, enhances job experience and satisfaction, and enables full-process smart traceability, providing a validated solution for endoscopy center logistics.

Progressive symmetric erythrokeratodermia(PSEK)is a rare hereditary skin disease charac-terized by symmetrical erythema,hyperkeratosis and multiorgan lesions.Its clinical phenotypes are highly heterogeneous and may be accompanied by symptoms such as thrombocytopenia,which can be fatal in se-vere cases.The genotype-phenotype association mechanism of PSEK is extremely complex.Currently,it is known that mutations in multiple genes such as GJB3,KDSR,and KRT83 can cause the disease.A-mong them,3-ketodihydrosphingosine reductase(KDSR)has been found to harbor nearly 20 clinical mu-tations.These mutations interfere with the de novo ceramide synthesis pathway,disrupt the homeostasis of the skin barrier,and cause platelet production disorders and multi-organ lesions,making it a current research hotspot in the molecular mechanism of PSEK.The pathogenic mutations of KDSR are widely and uniformly distributed throughout the entire protein,rather than being limited to the traditionally recog-nized active center,suggesting that the impairment of the KDSR enzymatic activity is not the only cause of PSEK.In view of this,this study selected four typical mutants of KDSR(KDSRQG55-56R,KDSRn38C,KDSRY186F,KDSRG182S),and first used recombinant expression technology to prepare pure and homoge-neous mutant proteins.Subsequently,thermal stability experiments as well as oligomerization analysis were conducted on these four mutant proteins.The results showed that the Tm values of the four mutants were significantly lower than that of the wild type.Particularly,KDSRF138C and KDSRQG55-56R were nearly completely denatured at physiological temperature.This result was perfectly consistent with the further Rosetta energy analysis.In conclusion,this study took several pathological mutations of the PSEK patho-genic factor KDSR as the research object and discovered that the conformational stability of KDSR might be closely related to the occurrence of PSEK pathogenicity,indicating that the imbalance of conformation-al homeostasis is very likely to be one of the common contributing factors of many genetic diseases,inclu-ding PSEK.This provides a new theoretical basis and reference for explaining the molecular mechanism of genotype-phenotype heterogeneity in many genetic diseases.

Objective:To evaluate the clinical utility of an intelligent endoscope transportation system in the digestive endoscopy center.Methods:A parallel-group controlled trial was conducted at Digestive Endoscopy Center of Qilu Hospital of Shandong University from June 1st to December 31st 2024, comparing robotic intelligent endoscope transport (experimental group) versus manual transport (control group). Performance metrics, including response time, transportation speed, labor efficiency, contamination prevention, closed-loop traceability, and nursing staff satisfaction, were statistically analyzed. Full-time equivalent (FTE) was introduced to quantify the operational efficiency of the experimental group.Results:The study included a total of 60 206 instances of intelligent endoscope transportation and 60 485 instances of manual transportation data. The robotic group demonstrated significantly shorter response times versus manual group for initial dispatch (51.08±14.97 seconds VS 54.44±13.61 seconds, t=35.8, P<0.001) and recovery response time (32.52±11.26 seconds VS 40.20±11.40 seconds, t=103.93, P<0.001). During the 148 days operational period, the success rate was 99.83% (60 104/60 206) and the failure rate was 0.17% (102/60 206) for robotic transports. Primary failure causes were wireless disconnection, pathfinding errors, and mechanical faults, averaging 1.05 malfunctions/month with no adverse events. The success and failure rate was 99.26% (60 043/60 485) and 0.74% (442/60 485) respectively for manual transports. Staff satisfaction was significantly higher for robotic transport in endoscopic transportation (4.65±0.55 scores VS 3.97±0.98 scores, t=96.5, P<0.001) and delivery process (4.71±0.59 scores VS 3.90±1.04 scores, t=210.3, P<0.001). and workload intensity was significantly lower (4.06±0.77 scores VS 4.48±0.63 scores, t=59.9, P=0.025). The system reduced labor requirements by 3.68 FTE, yielding annual savings of ￥657 000. Conclusion:The robotic intelligent endoscope transport system improves work efficiency, reduces nursing labor costs and physical workload, enhances job experience and satisfaction, and enables full-process smart traceability, providing a validated solution for endoscopy center logistics.

GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.

Objective To explore the characteristics of blood pressure in the elderly patients with hypertensive cerebral small vessel disease(CSVD)and their correlation with traditional Chinese medicine(TCM)syndrome types.Methods A retrospective analysis was conducted in 189 elderly patients with essential hypertension.With reference to the presence or absence of CSVD,the patients were divided into CSVD group(87 cases)and non-CSVD group(102 cases).The blood pressure related parameters and clinical data obtained by four diagnostic methods of TCM in the two groups were collected,and then the characteristics of blood pressure and their correlation with TCM syndromes were analyzed with statistical methods.Results(1)CSVD group had higher values than non-CSVD group in the ambulatory blood pressure parameters of 24-hour systolic blood pressure(24hSBP),24-hour diastolic blood pressure(24hDBP),daytime systolic blood pressure(DSBP),daytime diastolic blood pressure(DDBP),nighttime systolic blood pressure(NSBP),nighttime diastolic blood pressure(NDBP),24-hour pulse pressure(24hPP),daytime pulse pressure(DPP),nighttime pulse pressure(NPP),maximum SBP,morning SBP,daytime SBP load and nighttime SBP load(P＜0.01).(2)The analysis of blood pressure variability showed that the mean value of nighttime SBP standard deviation(NSSD)in CSVD group was higher than that in the non-CSVD group(P＜0.01).(3)The analysis of circadian rhythm of blood pressure showed that there was significant difference in the comparison of circadian rhythm of ambulatory blood pressure between the two groups(P＜0.05):non-CSVD group was predominated by non-dipper type blood pressure(50 cases,49.02%)and dipper type blood pressure(31 cases,30.39%),and CSVD group was predominated by non-dipper type blood pressure(38 cases,43.68%)and super-dipper type blood pressure(31 cases,35.63%).(4)Logistic regression analysis showed that 24hSBP(OR=1.296,95%CI:1.112-1.511),maximum SBP(OR=1.074,95%CI:1.006-1.146),morning SBP(OR=1.064,95%CI:1.013-1.118),abnormal circadian rhythm of blood pressure(OR=3.736,95%CI:1.663-8.390)were the influence factors of CSVD(P＜0.05 or P＜0.01).(5)The analysis of the distribution of TCM syndrome types showed that non-CSVD group was dominated by accumulation of excess phlegm-damp syndrome(58.82%)and yin deficiency and yang hyperactivity syndrome(21.57%),and CSVD group was dominated by yin deficiency and yang hyperactivity syndrome(51.72%)and accumulation of excess phlegm-damp syndrome(21.84%).(6)The analysis of blood pressure in patients with various syndrome types showed that the DPP of patients with accumulation of excess phlegm-damp syndrome in the CSVD group was significantly higher than that in the non-CSVD group(P＜0.01),and the 24hDBP and NDBP of patients with yin deficiency and yang hyperactivity syndrome in the CSVD group were significantly higher than those in the non-CSVD group(P＜0.01).Conclusion It is indicated that 24hSBP,maximum SBP,elevated morning SBP,and abnormal blood pressure circadian rhythms may be the important risk factors for the hypertensive CSVD in the elderly.Elderly hypertensive patients with accumulation of excess phlegm-damp syndrome should pay more attention to the mean daytime pulse pressure,and elderly hypertensive patients with yin deficiency and yang hyperactivity syndrome should pay more attention to monitoring DBP.The dynamic observation and early control of the blood pressure is helpful for the prevention and treatment of CSVD in the elderly patients with hypertension.

This study was aimed at understanding the Blastocystis,Enteroc ytozoon bieneusi,Cryptosporidium spp.,Gi-ardia duodenalis,and Pentatrichomonas hominis infection status in Chinese Milu deer(Elaphurus davidianus)in various prov-inces of China.A total of 81 fecal samples were collected from Beijing,Inner Mongolia,Hebei,and Hubei.PCR was used to detect the protozoans,and their subtypes and zoonoticity were determined through sequence and phylogenetic analyses.PCR re-sults indicated an infection prevalence of 40.74％,19.75％,and 8.64％for Blastocystis,E.bieneusi,and Cryptosporidium spp.,respectively,whereas G.duodenalis and P.hominis was not detected.Only one subtype of Cryptosporidium spp.(Cryptosporidium deer genotype)was detected.Four E.biene-usi genotypes were detected:HLJD-V,MWC-d1,BEB6,and CGC2.Five Blastocystis ST types were found:ST10,ST14,ST21,ST23,and ST25.Cryptosporidium spp.,E.bieneusi,and Blastocystis infections were prevalent,and zoonotic subtypes or genotypes of E.bieneusi and Blastocystis were i-dentified.The prevention and control of intestinal protozoa in Chinese Milu deer would support population health and is im-portant for public health.

This study was aimed at understanding the Blastocystis,Enteroc ytozoon bieneusi,Cryptosporidium spp.,Gi-ardia duodenalis,and Pentatrichomonas hominis infection status in Chinese Milu deer(Elaphurus davidianus)in various prov-inces of China.A total of 81 fecal samples were collected from Beijing,Inner Mongolia,Hebei,and Hubei.PCR was used to detect the protozoans,and their subtypes and zoonoticity were determined through sequence and phylogenetic analyses.PCR re-sults indicated an infection prevalence of 40.74％,19.75％,and 8.64％for Blastocystis,E.bieneusi,and Cryptosporidium spp.,respectively,whereas G.duodenalis and P.hominis was not detected.Only one subtype of Cryptosporidium spp.(Cryptosporidium deer genotype)was detected.Four E.biene-usi genotypes were detected:HLJD-V,MWC-d1,BEB6,and CGC2.Five Blastocystis ST types were found:ST10,ST14,ST21,ST23,and ST25.Cryptosporidium spp.,E.bieneusi,and Blastocystis infections were prevalent,and zoonotic subtypes or genotypes of E.bieneusi and Blastocystis were i-dentified.The prevention and control of intestinal protozoa in Chinese Milu deer would support population health and is im-portant for public health.

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ² analysis, and a paired χ² test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ²=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ²=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ²=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ²=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ²=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.