Efficacy and Safety Study of Thymalfasin in Combination with Targeted Immunotherapy (Regorafenib and Tislelizumab) in Patients with Advanced PMMR/MSS Colorectal Cancer Who Failed Standard of Care: a Multicenter, Open-label, Randomized, Controlled Clinical Study

This is a multicenter, open-label, prospective, randomized controlled Phase II clinical study. All eligible subjects will be randomly assigned in a 1:1 ratio to either the triple therapy group or the double therapy group.
Triple therapy group: Subjects will receive Thymalfasin in combination with Regorafenib and Tislelizumab until iCPD is achieved per iRECIST (progressive disease (PD) per iRECIST), or until an intolerable toxicity occurs; Double therapy group: Subjects will receive Regorafenib and Tislelizumab until iCPD is achieved per iRECIST (PD per iRECIST), or until an intolerable toxicity occurs.

Start Date11 Feb 2025

Sponsor / Collaborator

Beijing Friendship Hospital

[+2]

NCT06821100

/ RecruitingPhase 1IIT

Thymalfasin (Thymosin Alpha 1; Ta1) as an Enhancer of Vaccine Response Among Older Adults Receiving Booster Doses of COVID-19 Vaccine

The goal of this research is to learn more about ZADAXIN® (trade name; thymalfasin generic; Ta1 for short) and determine if Ta1 has any benefit in increasing the immune response to the COVID-19 vaccine. Ta1 has been shown to stimulate the immune system to fight infections.
This research study will test the safety and possible harms of Ta1 when it is given to people at different dose levels before COVID-19 vaccination.

Start Date02 Dec 2024

Sponsor / Collaborator

The Methodist Hospital Research Institute

NCT06607926

/ Not yet recruitingNot ApplicableIIT

Efficacy and Safety of Thymosin α1 Plus Immune Checkpoint Inhibitors and Chemotherapy as Neoadjuvant Therapy in Patients With Resectable Stage II - IIIB Non Small Cell Lung Cancer: A Prospective, Multicenter, Randomized, Controlled Trial

This study aims to explore the efficacy and safety of thymosin α-1 (Tα1) plus chemotherapy and PD-1 inhibitors as neoadjuvant therapy for operable non-small cell lung cancer

Start Date15 Oct 2024

Sponsor / Collaborator

Xuanwu Hospital Capital Medical University

100 Clinical Results associated with Thymalfasin

100 Translational Medicine associated with Thymalfasin

100 Patents (Medical) associated with Thymalfasin

1,248

Literatures (Medical) associated with Thymalfasin

31 Dec 2025·DRUG DELIVERY

Exploiting the potential of in situ forming liquid crystals: development and in vitro performance of long-acting depots for peptide drug thymosin alpha 1 subcutaneous administration

Article

Author: Matjaž, Mirjam Gosenca ; Zvonar Pobirk, Alenka ; Roškar, Robert ; Vitek, Mercedes

The fast-growing filed of long-acting depots for subcutaneous (SC) administration holds significant potential to enhance patient adherence to treatment regimens, particularly in the context of chronic diseases. Among them, injectable in situ forming lyotropic liquid crystals (LCCs) consisting of hexagonal mesophases represent an attractive platform due to their remarkable highly ordered microstructure enabling the sustained drug release. These systems are especially relevant for peptide drugs, as their use is limited by their short plasma half-life and inherent poor stability. In this study, we thus aimed to exploit the potential of a liquid crystalline platform for the sustained release of peptide drug thymosin alpha 1 (Tα1), characterized by a short plasma half-life and with that associated twice-weekly SC administration regimen. We initially selected specified ingredients, with ethanol serving to reduce viscosity and stabilize the peptide drug Tα1, lecithin contributing to LCCs formation and stabilization, and glycerol monooleate or glycerol monolinoleate representing the hexagonal LCCs forming matrix material. The selected studied nonaqueous precursor formulations were characterized by suitable rheological properties for SC injection. A convenient and rapid in situ phase transition of precursor formulations to hexagonal LCCs, triggered by water absorption, was successfully accomplished in vitro. Notably, in situ formed LCCs demonstrated sustained release kinetics of the peptide drug Tα1 for up to 2 weeks of in vitro release testing, offering minimized dosing frequency and thus promoting patient adherence. In summary, the newly developed in situ forming liquid crystalline systems represent prospective injectable long-acting depots for SC administration of the peptide drug Tα1.

01 May 2025·CHEMICO-BIOLOGICAL INTERACTIONS

Small molecule as potent hepatocellular carcinoma progression inhibitor through stabilizing G-quadruplex DNA to activate replication stress responded DNA damage

Article

Author: Zeng, Yongchang ; Huang, Fei ; Mei, Wenjie ; Huang, Jinhua ; He, Dongqing ; Wu, Qiong ; Zhao, Bin ; Liu, Yan

G-quadruplex (G4) DNA, prevalent in tumor cells, offers a potential anticancer target. This study examined TA-1, a tanshinone IIA derivative, for its antitumor activity against liver cancer. We found that TA-1 binds and stabilizes multiple G4 DNA,triggering DNA damage, suppressing the angiogenesis in vitro and in vivo and leading to cancer cell death. Notably, we confirmed TA-1's inhibitory effect on liver cancer cells and explored its mechanism, which involves stabilizing G4 DNA to mediate replication-stress-dependent DNA damage. Furthermore, TA-1 promotes 53BP1 expression, activating toxic NHEJ repair and leading to apoptotic cell death via the ATM-Chk2-p53 pathway. In vivo studies further supported these findings. In summary, TA-1 is a potent VEGF G-quadruplex stabilizer that inhibits liver cancer progression.

01 May 2025·CLINICAL THERAPEUTICS

The Effect of Ulinastatin on Sepsis Outcomes: An Umbrella Review of Meta-Analysis

Review

Author: Han, Ping ; Cao, Sheng

OBJECTIVES:

Sepsis, a multifaceted disorder, emerges from dysregulated host response to infection, culminating in organ dysfunction and heightened risk of mortality. Present umbrella systematic review was conducted to impart accurate data regarding the effect of urinary trypsin inhibitor (UTI) alone, UTI in combination with thymosin α1, and UTI in combination with Xuebijing on sepsis and inflammation, 28-day mortality rate survival day, time of mechanical ventilation, length of intensive care unit stay, and acute physiology and chronic health evaluation (APACHE II) score.

METHODS:

Relevant studies were searched in international databases, including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central Library up to March 2024. Our study included meta-analyses that evaluated the effects of ulinastatin (UTI) alone, or in combination with thymosin α1 or Xuebijing, on sepsis and inflammatory biomarkers.

RESULTS:

Nine studies were deemed relevant and subsequently included in the study. The age of the study's participants was between 42.3 and 55.7 years. In total, the dose varied between 166 and 570 KIU/12 h. Moreover, the duration varied between 3 and 8.5 days.

CONCLUSION:

A comprehensive assessment of ulinastatin's overall efficacy necessitates a careful consideration of the combined effects of ulinastatin with other interventions. Future research is warranted to disentangle the specific contributions of ulinastatin in combination therapies and to enhance our understanding of its independent effects in clinical settings.

News (Medical) associated with Thymalfasin

29 Mar 2024

·www.pharmaceutical-technology.com

Gilead’s Vemlidy expands label to treat paediatric chronic HBV

Vemlidy is approved to treat patients six years and older for chronic HBV. Credits: Sundry Photography/Shutterstock.com Soon after GSK gained traction with a US Food and Drug Administration (FDA) fast track designation for its investigational treatment bepirovirsen for chronic hepatitis B virus (HBV), Gilead Sciences has strengthened its position in the indication with an FDA approval for Vemlidy (tenofovir alafenamide) to treat paediatric patients. The once daily 25mg tablets have been greenlit to treat patients with chronic HBV with compensated liver disease that are six years and older and weigh at least 25kg. The supplemental new drug application (sNDA) approval was based on data from the ongoing Phase II Study 1092 (NCT02932150), comparing the safety and efficacy of 25mg Vemlidy to placebo in 88 treatment-naïve and treatment-experienced patients with chronic HBV. As per a 28 March press release, patients treated with Vemlidy and those that switched to open-label Vemlidy after week 24 demonstrated “progressive increases in rates of virological suppression” by week 96. “The expanded indication for Vemlidy for the treatment of children as young as six years old is a testament to the safety, tolerability and efficacy profile of this therapy,” said Dr. Frank Duff, Gilead’s senior vice president of the virology therapeutic area, in the announcement. The pharma giant aims to continue addressing unmet treatment needs for children, he added. Vemlidy, a small molecule nucleoside analogue reverse transcriptase inhibitor, was first FDA approved in 2016 as a treatment for adults with chronic HBV and gained its first label expansion in 2022 to treat patients aged 12 years and older with compensated liver disease. The product is marketed with a boxed warning for post-treatment severe acute exacerbation of hepatitis B. See Also: Angelini gets grant for method for labelling reels using robot and application roller Rohto Pharmaceutical gets grant for ophthalmic composition for treating myopia with crocetin and ginkgo leaf GlobalData’s drugs database forecasts that the hepatitis B treatment market will significantly increase over the next six years to reach $10.5bn in 2029, with analysts predicting a compound annual growth rate of 30%. According to the analysts, 71% of the sales in 2022 were attributed to Vemlidy and SciClone Pharmaceuticals’ Zadaxin, a synthetic polypeptide, indicating market dominance. GlobalData’s consensus forecasts predict that Vemlidy will generate $873m in sales in 2024. GlobalData is the parent company of Pharmaceutical Technology .

Drug ApprovalClinical ResultPhase 2Fast Track

27 Feb 2024

·www.businesswire.com

Sepsis Drug Pipeline Research Report 2024: Insights from 30 Companies and 35 Pipeline Drugs - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "Sepsis - Pipeline Insight, 2024" clinical trials has been added to ResearchAndMarkets.com's offering. This report provides comprehensive insights about 30+ companies and 35+ pipeline drugs in Sepsis pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. The report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Sepsis pipeline landscape is provided which includes the disease overview and Sepsis treatment guidelines. The assessment part of the report embraces, in depth Sepsis commercial assessment and clinical assessment of the pipeline products under development In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Sepsis collaborations, licensing, mergers and acquisition, funding, designations and other product related details. Report Highlights The companies and academics are working to assess challenges and seek opportunities that could influence Sepsis R&D. The therapies under development are focused on novel approaches to treat/improve Sepsis. Sepsis Emerging Drugs Chapters This segment of the Sepsis report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Sepsis Emerging Drugs Thymosin alpha 1: SciClone Pharmaceuticals Thymosin alpha 1, referred to as thymalfasin, is a synthetic 28-amino acid peptide with multiple biological activities primarily directed towards immune response enhancement. SciClone developed and launched Thymosin alpha 1, under the trade name Zadaxin, for the treatment of hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infections. The drug is also being developed for the treatment of COVID 2019 infections. Scientific and clinical studies have shown that Thymosin alpha 1 helps to stimulate and direct the body's immune response to eradicate infectious diseases, such as HBV, HCV, bacterial, and fungal infections; to fight certain cancers such as melanoma and liver cancer; and to enhance response to vaccines. Clinical trials have shown that Thymosin alpha 1 improves survival in patients in intensive care units being treated for sepsis from severe bacterial infections. The therapy is being evaluated in Phase III stage to treat Sepsis. Currently, the drug is in Phase III stage of its development for the treatment of sepsis. Enibarcimab: AdrenoMed AG Enibarcimab (HAM8101; former name: Adrecizumab) a clinical-stage, first-in-class drug targeting loss of vascular integrity. The strong rationale for Enibarcimab is supported by the elegance of its mode of action, a monoclonal antibody that on binding to its target Adrenomedullin preserves its functionality as regulator of vascular integrity. Enibarcimab targets Adrenomedullin (ADM), a vasoprotective peptide hormone. ADM that remains in the bloodstream, however, has a different effect, one that helps mitigate sepsis: promoting stability of the endothelial barrier by restoring the cell junctions between endothelial cells that ordinarily regulate molecule transport and leakage. In health, levels of ADM in the bloodstream and extravascular space are in equilibrium so that endothelial barrier integrity is maintained and blood pressure remains normal. Currently, the drug is in Phase II stage of its development for the treatment of sepsis. M 6229: Matisse Pharmaceuticals Matisse's platform technology is based on the discovery that in many patients suffering from sepsis, proteins called histones are released by the innate immune system and dying cells into the blood stream, where they are toxic to other cells. Due to a self-enforcing cascade, people may die from organ failure within one or two days. Preclinical results have shown that by neutralizing the toxic histones with Matisse's product M6229, the negative cascade is terminated by neutralization of cationic histones by anionic M6229. Matisse claims to have identified an elegant solution for treating one of the major complications in sepsis by using a non-anticoagulant fraction of heparin called M6229 to neutralize toxic circulatory histones .Currently, the drug is in Phase I stage of its development for the treatment of sepsis. SNIPR 001: SNIPR Biome SNIPR001 is a novel, orally-administered antibiotic that is designed to precisely target difficult-to-treat bacterial infections. It is developed using SNIPR Biome's CRISPR-Guided VectorsT (CGVT Technology), which is designed to deliver CRISPR reagents into target bacterial cells. SNIPR001 is designed to target certain E. coli bacteria in the gut and thus prevent their translocation to the bloodstream, without affecting beneficial bacteria in the microbiome. It contains four CRISPR-armed phages that selectively target and eliminate E. coli strains that are resistant to fluoroquinolone, with demonstrated efficacy in animal disease models. Currently, the drug is in preclinical stage of its development for the treatment of sepsis. Sepsis: Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Sepsis therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Sepsis drugs. Sepsis: Therapeutic Assessment Phases Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Products have been categorized under various ROAs such as Oral Intravenous Subcutaneous Parenteral Topical Molecule Type Products have been categorized under various Molecule types such as Recombinant fusion proteins Small molecule Monoclonal antibody Peptide Polymer Gene therapy Product Type Sepsis Report Insights Sepsis Pipeline Analysis Therapeutic Assessment Unmet Needs Impact of Drugs Sepsis Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Players SciClone Pharmaceuticals AdrenoMed AG Matisse Pharmaceuticals SNIPR Biome Tianjin Chase Sun Pharmaceutical Beijing Scitech-Mq Pharmaceuticals Recce Pharmaceuticals Inotrem Octapharma Shaperon Shionogi Pharmazz Seres Therapeutics Key Products Thymosin alpha 1 Enibarcimab M 6229 SNIPR 001 Kukoamine B ST-1830 RECCE 327 Nangibotide OctaplasLG HY209 Cefiderocol Centhaquine SER 155 For more information about this clinical trials report visit https://www.researchandmarkets.com/r/ixi7k5 About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

Phase 2Phase 3Phase 1

08 Jun 2017

·www.biospace.com

Investment Group Just Paid $605 Million for This Bay Area Pharma

June 8, 2017 By Mark Terry , BioSpace.com Breaking News Staff SciClone Pharmaceuticals , located in Foster City, Calif., agreed to be acquired for $605 million by a consortium of buyers. The consortium is made up of GL Capital Management CP , Bank of China Group Investment , CDH Investments , Ascendent Capital Partners and Boying . SciClone is a specialty pharmaceutical company with significant commercial business in China. Its portfolio covers oncology, infectious diseases and cardiovascular disorders. Its lead product is Zadaxin (thymalfasin) for hepatitis B, hepatitis C and some cancers, and is approved in over 30 countries. The Buyer Consortium that is acquiring the company will buy all the outstanding shares of SciClone for $11.18 per share in cash. It will be funded by the consortium via a combination of equity financing and debt financing. The $605 million figure is a premium of about 11 percent over its stock price on June 7, and a premium of more than 16 percent over its 10-day volume-weighted average closing stock price. The bid was first announced in November 2016. “The Board has determined that a sale of the Company at this time is the best way to deliver meaningful value to SciClone’s stockholders,” said Jon Saxe , SciClone’s chairman of the board, in a statement. “While SciClone has executed well on its growth strategies to date, following continued review of its strategic alternatives, the Board has determined that the challenges of continuing to operate as an independent U.S.-based, publicly traded company in the complex, competitive and increasingly price-sensitive China pharmaceuticals market represents long-term risks to the Company’s ability to maintain a strong growth trajectory and to meet its financial objectives. This agreement enables SciClone stockholders to achieve substantial cash value and premium to the Company’s recent trading price in the near term and eliminates exposure to long-term risk and uncertainty.” On May 10, the company reported its first-quarter financial results . It announced first-quarter revenues of $42.9 million, an 18 percent increase from $36.5 million from the same period the year before. First period Zadaxin revenues were $39.5 million, up 17 percent from $33.6 million in the first quarter of 2016. “We delivered a strong first quarter performance, in line with our expectations, and reflecting the continued demand for, and growth potential of, Zadaxin and our core business,” said Friedhelm Blobel , SciClone’s chief executive officer, in a statement. “Zadaxin’s competitive position remains strong, with continued volume growth despite generic competition. Zadaxin’s double-digit volume growth rate continued this quarter, underscoring its strength as the leading branded thymalfasin, with a 17 percent volume share and more than a 40 percent value share. We do face continued pricing pressure, with tenders in two provinces recently announced at prices lower than the reference price with our distributor. We cannot determine at this time with certainty when these prices will take effect, or when they will impact prices in other provinces, but we are likely to experience some effect of those lower prices at some point during the next few quarters. We may also see some pressure on unit volumes in some areas as a result of reduced national-level reimbursement for thymalfasins.” SciClone Pharmaceuticals is currently trading for $10.90.

AcquisitionDrug ApprovalBiosimilarFinancial StatementIPO

100 Deals associated with Thymalfasin

External Link

KEGG	Wiki	ATC	Drug Bank
D06116	-	A05A	DB04900

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatitis B, Chronic	China	Sciclone Pharmaceuticals Italy Srl	01 Jan 1996
Hepatitis C	-	-	-

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Sepsis	Phase 3	China	SciClone Pharmaceuticals LLC	06 Sep 2016
Hepatitis C, Chronic	Phase 3	United States	SciClone Pharmaceuticals LLC	01 Apr 2002
Hepatitis C, Chronic	Phase 3	Puerto Rico	SciClone Pharmaceuticals LLC	01 Apr 2002
Advanced Malignant Solid Neoplasm	Phase 2	China	SciClone Pharmaceuticals LLC	01 Apr 2023
Influenza, Human	Phase 2	Italy	Alfasigma SpA	01 Nov 2009
Kidney Failure, Chronic	Phase 2	Italy	Alfasigma SpA	01 Nov 2009
Hepatocellular Carcinoma	Phase 2	United States	SciClone Pharmaceuticals LLC	28 Apr 2004
Malignant melanoma, metastatic	Phase 2	France	Alfasigma SpA	01 Jul 2002
Malignant melanoma, metastatic	Phase 2	Germany	Alfasigma SpA	01 Jul 2002
Malignant melanoma, metastatic	Phase 2	Hungary	Alfasigma SpA	01 Jul 2002

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02867267 (TESTS, Pubmed)	Phase 3	Sepsis	1,106	Thymosin α1	pefelcndsr(ofbwkfeawd) = zyyvgtunia xishuhaoxa (vzxwmregwr )	Negative	15 Jan 2025
				Placebo	pefelcndsr(ofbwkfeawd) = ehdazerung xishuhaoxa (vzxwmregwr )
NCT05790447 (PRaG 5.0 Study, ASTRO2024)	Phase 2	Metastatic Solid Tumor T lymphocyte count	6	PRaG regimen + Thymalfasin	omwmssdokg(jthpbjjjhn) = ojbunurrub teedgybwji (ycljjuzhzz ) View more	Positive	01 Oct 2024
NCT04963712 (Pubmed \| BMC Infect Dis) Manual	Early Phase 1	HIV Infections PD-1 \| TIM-3 \| sjTREC	20	Thymosin α1 1.6 mg	nwrxeqqlwu(zujfytpzss) = tknmrblkcx dzzxstpnhh (ffrrhdwoxb ) View more	Positive	17 Jan 2024
				Thymosin α1ral therapy	nwrxeqqlwu(zujfytpzss) = nxgvpccccw dzzxstpnhh (ffrrhdwoxb ) View more
GASTO-1043 (Pubmed)	Phase 2	Radiation Pneumonitis \| Locally Advanced Lung Non-Small Cell Carcinoma	69	Thymosin α1 + CCRT	xwiiufcwkj(egdxmtgeuj) = zgidupdfhe dmhvknvlkz (qogmigmhje ) View more	Positive	20 Jul 2022
				CCRT alone	lvbzwrbfrq(dnipdvanxh) = hnekiymdrj jckuaeupqw (rehqnlkzlf ) View more
Pubmed \| Front Immunol	Not Applicable	COVID-19	-	Thymosin Alpha 1	lgbhremloo(bsqsfhsjyx) = bcihmkrxzv hbshhjsdmi (mmdznqvhrw )	-	02 Aug 2021
				Non-Thymosin Alpha 1	lgbhremloo(bsqsfhsjyx) = zrirpuuqtm hbshhjsdmi (mmdznqvhrw )
ICML2017	Not Applicable	Diffuse Large B-Cell Lymphoma	-	R-CHOP plus thymosin α1	vohldgxszo(jaywazexwb) = jsqrmxcfqm qhbipfirvn (vcmbfswiju ) View more	Positive	07 Jun 2017
				R-CHOP	vohldgxszo(jaywazexwb) = knpgnwspkz qhbipfirvn (vcmbfswiju ) View more
NCT01178996 (Pubmed \| J Viral Hepat)	Phase 3	Hepatitis C, Chronic Adjuvant	552	Thymosin alpha-1 + Peginterferon alfa-2a/Ribavirin	wgoabaacyx(ilntbhtayj) = ykzvswpihw bmkxwvcnco (lokacvxgdw )	-	01 Jan 2012
				Placebo + Peginterferon alfa-2a/Ribavirin	wgoabaacyx(ilntbhtayj) = ovcsirknid bmkxwvcnco (lokacvxgdw )
NCT00911443 (CTgov)	Phase 2	Malignant melanoma, metastatic	488	Interferon Alpha+Dacarbazin+Thymosin-alpha-1 (Dacarbazin + Interferon Alpha + Thymosin-alpha-1 1.6 mg)	xwavitbgop = btewzzchxs lssqrbbcwi (knzmyaqrrq, culttnxzml - imydtnvtgt) View more	-	02 Jun 2009
				Interferon Alpha+Dacarbazin+Thymosin-alpha-1 (Dacarbazin + Interferon Alpha + Thymosin-alpha-1 3.2 mg)	xwavitbgop = wnfhufcifp lssqrbbcwi (knzmyaqrrq, gzvyngepio - gofyxjwnov) View more
ASCO2005	Not Applicable	Advanced breast cancer	18	thymalfasin (Group 1)	xokajpnxsl(edpwzrgtjy) = jnzoitsvkm ssdfgehxcb (lpfrpyxfas )	-	01 Jun 2005
				thymalfasin (Group 2)	jkudhwpxie(fuonfcsnmg) = tsmlhrihga qudqzoerls (lebtsyhvjg )

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